Microbiology Flashcards
What are the four processes that occur in septicaemia?
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
What is a typical MRI feature of TB meningitis?
Leptomeningeal enhancement
Name two types of amoeba that cause encephalitis.
Naegleria fowleri
Acanthamoeba species and Balamuthia mandrillaris
What is toxoplasmosis and how is it spread?
Obligate intracellular parasite
Spread via oral, transplacental or organ transplant route
From raw/undercooked meats (particularly in France) and contact with cat faeces
List some organisms that can cause brain abscesses.
Staphylococci Streptococci Gram-negative organisms (mainly in neonates) TB Actinomyces and Nocardia species
Describe the Gram-stain and microscopic appearance of:
a. S. pneumoniae
b. N. meningitidis
c. L. monocytogenes
d. TB
e. Cryptococcus
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)
What is another key clinical feature of Cryptococcal meningitis?
High opening pressure
What is the generic therapy used in meningitis?
Ceftriaxone 2 g IV BD
If > 50 years or immunocompromised = amoxicillin 2 g IV 4 hourly
NOTE: this is because ceftriaxone does NOT cover Listeria
What is the generic therapy used in meningo-encephalitis?
Aciclovir 10 mg/kg IV TDS
Ceftriaxone 2 g IV BD
If > 50 years or immunocompromised = amoxicillin 2 g IV 4 hourly
Name the specific therapy for meningitis caused by:
a. S. pneumoniae
b. N. meningitidis
c. H. influenzae
d. Group B Streptococcus
e. Listeria
f. Gram-negative bacilli
g. Pseudomonas
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
What type of toxin is produced by Staphylococcus aureus?
Enterotoxin – this is an exotoxin that can act as a superantigen in the GI tract triggering the release of IL1 and IL2
What type of organism is Bacillus cereus?
Gram-positive rods that are spore-forming
Name three types of Clostridium infection and describe the diseases that they cause.
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
Which antibiotics are most commonly implicated in C. difficile colitis?
Cephalosporins
Clindamycin
Ciprofloxacin
What type of organism is Listeria monocytogenes?
Gram-positive, rod-shaped, facultative anaerobe
Beta-haemolytic, aesculin-positive with tumbling motility
What type of organisms are Enterobacteriaceae?
Facultative anaerobes
Lactose fermenters
Oxidase-negative
What type of bacteria are Salmonella enteritidis?
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
Which antigens are found on Salmonellae?
Cell wall O (groups A-I)
Flagellar H
Capsular Vi (virulence, antiphagocytic)
NOTE: differences in these antigens help identify types of Salmonellae
Describe the presentation of Salmonella typhi.
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
How is Salmonella typhi treated?
Ceftriaxone
List some types of Shigella.
Shigella sonnei
Shigella dysenteriae
Shigella flexneri (MSM)
NOTE: avoid antibiotic treatment (use ciprofloxacin if necessary)
What are the microbiological features of Vibrio?
Comma-shaped
Late lactose-fermenters
Oxidase-positive
Gram-negative
Name and describe the key features of other types of Vibrio.
Vibrio parahaemolyticus – caused by ingestion of raw/undercooked seafood, causes self-limiting diarrhoea, grows on salty agar
Vibrio vulnificus – causes cellulitis in shellfish handlers, can cause fatal septicaemia with D&V in HIV patients, treated with doxycycline
What are the main microbiological features of Campylobacter?
Comma-shaped Microaerophilic Oxidase-positive Gram-negative Motile
What are the key microbiological features of Entamoeba histolytica?
Motile trophozoite in diarrhoeal illness
Non-motile cyst in non-diarrhoeal illness
Killed by boiling
Contains four nuclei
No animal reservoir
Describe the pathophysiology of diarrhoeal illness caused by Entamoeba histolytica?
Ingestion of cysts trophozoites move into the ileum colonise the colon causes flask-shaped ulcers
How is Entamoeba histolytica infection diagnosed and treated?
Diagnosis: stool microscopy, serology of invasive disease
Treatment: metronidazole + paromomycin
What are the key microbiological features of Giardia lamblia?
Pear-shaped trophozoites
Two nuclei
Four flagellae and a suction disc
Outline the pathophysiologiy of GI disease caused by Giardia.
Transmitted by ingestion of cyst from faecally contaminated water
Excystation in the duodenum leads to trophozoite attachment
Results in malabsorption of protein and fat
Presentation: foul-smelling non-bloody diarrhoea, cramps, flatulence, NO fever
What are the main features of Cryptosporidium parvum?
Causes severe diarrhoea in the immunocompromised
Oocysts can be seen in the stool using modified Kinyoun acid fast stain
Rx: paromomycin
Which stain is used to identify PCP?
Silver stain (Grocott-Gomori stain)
Which organisms do the following defects make you susceptible to?
a. T cell defect
b. B cell defect
c. Neutrophil defect
d. Complement defect
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
What is Actinomyces and what does it cause?
Gram-positive rod that causes lung abscesses in immunocompromised patients (particularly alcoholics)
NOTE: it’s closely associated with Nocardia
Describe the histological features of Actinomyces.
Basophilic sulfur granules
Gram-positive rods that branch as they grow
How is non-severe C. difficile disease treated?
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
Describe the MRI appearance of sporadic CJD.
Increased signal in the basal ganglia
Increased intensity on DWI MRI of the cortex and basal ganglia
On which chromosome is the normal prion gene found?
20
On which codon are the three polymorphisms of prion proteins found? What are the three polymorphisms?
Codon 129 MM (predisposes to prion diseases) MV VV NOTE: M = methionine, V = valine
Which gene mutation is associated with prion diseases?
PRNP
Which investigation is most useful for vCJD?
Tonsillar biopsy – prions localise in lymphoid tissue
NOTE: this is not useful in CJD
Outline the clinical features of iatrogenic CJD.
Starts with progressive ataxia
Dementia and myoclonus occur at a later stage
Describe the clinical features of Gerstmann-Straussler-Sheinker syndrome.
Slowly progressive ataxia
Diminished reflexes
Dementia
NOTE: PRNP P102L mutation is most common
Describe the clinical features of fatal familial insomnia.
Untreatable insomnia Dysautonomia (blood pressure and heart rate dysregulation) Ataxia Thalamic degeneration NOTE: PRNP D178N mutation is most common
What number of white cells in the urine represents inflammation?
More than 10^4/mL
In which patient groups should screening of the urine for white cells before MC&S NOT be performed?
Immunocompromised patients, pregnant women and children
List some causes of sterile pyuria.
STIs (e.g. chlamydia) TB Prior antibiotic treatment (MOST COMMON) Calculi Catheterisation Bladder cancer
What type of agar is used for urine culture? What do the colours suggest?
Chromogenic agar
• Pink = E. coli
• Blue = other coliforms
• Light blue = Gram-positives
In which groups of patients is a short course of antibiotics not appropriate?
Women with a history of UTI caused by antibiotic resistant organisms
More than 7 days of symptoms
Men
Which part of the kidney is more susceptible to infection?
Renal medulla
NOTE: the kidney is a frequent site for abscesses in patients with S. aureus endocarditis
What is the main treatment option for pyelonephritis?
Co-amoxiclav with or without gentamicin
What is the incubation period for hepatitis A?
2-6 weeks
Describe the molecular organisation of hepatitis B virus.
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
What is a strong indicator of risk of cirrhosis in people with hepatitis B infection?
HBV DNA level (copies/mL)
What components constitute the viral RNA genome of hepatitis C?
Core
Envelope
Non-structural components
NOTE: most drugs used for hep C are protease inhibitors
What is the incubation period of HCV?
6-8 weeks
List some treatment options for chronic HBV.
Interferon alpha Lamivudine Tenofovir Entecavir Emtricitabine
How is HCV treated?
Early treatment with peginterferon alfa
How is the response to treatment with peginterferon-alfa assessed in HCV infection?
Sustained viral response (SVR12) – no HCV RNA 12 weeks after stopping treatment
NOTE: SVR 24 can also be done
What is the main difference in the treatment of genotype 1 and non-genotype 1 HCV?
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
Outline the treatment of hepatitis E.
Supportive
Ribavirin
Name three major pathogens that cause surgical site infections.
Staphylococcus aureus
Escherichia coli
Pseudomonas aeruginosa
What are the three levels of surgical site infections?
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
List some bacterial factors that enable bacteria to cause septic arthritis.
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
List some host factors that increase the risk of septic arthritis.
Leukocyte-derived proteases and cytokines
Raised intra-articular pressure
Deletion of macrophage-derived cytokines
Absence of IL-10
Outline the presentation of chronic osteomyelitis.
Pain
Brodie’s abscess
Sinus tract
Name two techniques for treating chronic osteomyelitis.
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
Which organism most commonly causes prosthetic joint infection?
Coagulase-negative staphylococcus
Others: streptococci, enterococci, enterobacteriaciae, Pseudomonas aeruginosa, anaerobes
How is prosthetic joint infection diagnosed?
Radiology – shows loosening of the prosthesis
CRP > 13.5 for prosthetic knees
CRP > 5 for prosthetic hips
Joint aspiration (>1700/mL if knee; >4200/mL if hip)
How should specimens be taken intraoperatively?
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
List 5 HAIs in order of prevalence.
Pneumonia Surgical site infection UTI Blood stream infection Gastrointestinal infection
Define pyrexia of unknown origin.
A fever > 38.3 degrees lasting > 3 weeks with an uncertain diagnosis after 7 days in hospital
List some differentials for PUO.
Infection • Infectious endocarditis • HIV • TB Inflammation • Polymyalgia rheumatica • Still’s disease • Sarcoidosis • ANCA-associated vasculitis • Rheumatoid arthritis Malignancy • Malignant lymphoma • Castleman’s disease
List some infectious causes of PUO.
Bacteria • TB/NTM • Enteric fever (e.g. Salmonella typhi) • Zoonoses Viruses • EBV/CMV • HIV • Hepatitis Fungi • Cryptococcosis • Histoplasmosis Parasites • Malaria • Amoebic liver abscess • Schistosomiasis • Toxoplasmosis • Trypanosomiasis
What are the different components of EBV serology?
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
List two causes of very high ferritin.
Adult-onset Still’s disease
Macrophage activation syndrome
Outline the major and minor criteria for infective endocarditis.
Major • Persistent bacteraemia (> 2 positive blood cultures) • Vegetations on echocardiogram • Positive serology for Bartonella, Coxiella or Brucella Minor • Predisposition (murmur, IVDU) • Raised inflammatory markers • Immune complexes (RBC in urine) • Embolic phenomena (Janeway lesions) • Atypical echo • 1 positive blood culture 2 major + 1 minor OR 3 minor = infective endocarditis
IMPORTANT: 3 blood cultures should be taken in suspected infective endocarditis
Outline the key features of Adult-onset Still’s disease.
Salmon pink rash Arthralgia Sore throat Lymphadenopathy Fever
List some miscellaneous causes of PUO.
Subacute thyroiditis
Addison’s disease
PE
Dressler’s syndrome
Drugs – idiosyncratic or adverse drug reaction
NOTE: 25% of drug reactions will cause eosinophilia and a rash
Give examples of zoonoses in the UK that are transmitted by:
a. Farm/wild animals
b. Companion animals
a. Farm/wild animals Campylobacter Salmonella b. Companion animals Toxoplasmosis Bartonella Ringworm Psittacosis
For Campylobacter, describe the following:
a. Reservoir
b. Transmission
c. Clinical presentation
d. Investigations
e. Management
a. Reservoir Poultry Cattle b. Transmission Contaminated food c. Clinical presentation Bloating Diarrhoea Cramps d. Investigations Stool culture e. Management Supportive
For Salmonella, describe the following:
a. Reservoir
b. Transmission
c. Clinical presentation
d. Investigations
e. Management
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
For Cat Scratch Disease, describe the following:
a. Presentation
b. Investigations
c. Management
a. Presentation Macule at site of inoculation Becomes pustular Regional adenopathy Systemic symptoms (FLAWS) b. Investigations Serology c. Management Erythromycin Doxycycline
For baciliary angiomatosis, describe the following:
a. Presentation
b. Investigations
c. Management
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
For Toxoplasmosis, describe the following:
a. Reservoir
b. Transmission
c. Clinical presentation
d. Investigations
e. Management
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
For Brucellosis, describe the following:
a. Reservoir
b. Transmission
c. Clinical presentation
d. Investigations
e. Management
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
Which two infectious agents can cause rat bite fever?
Streptobacillus moniliformis
Spirilum minus
For rat bite fever, describe the following:
a. Reservoir
b. Transmission
c. Clinical presentation
d. Investigations
e. Management
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
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
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
What medium is Legionella grown on?
Buffered charcoal yeast extract
How is PCP investigated?
Bronchoalveolar lavage
How is invasive aspergillosis treated?
Amphotericin B
Which organisms cause pneumonia in the following subgroups of patients:
a. HIV
b. Neutropaenia
c. Bone marrow transplant
d. Splenectomy
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)
Which respiratory organism is investigated using immunofluorescence?
PCP
NOTE: PCP can also be detected using silver stain
What are the 1st and 2nd line treatment options for HAP?
1st = ciprofloxacin +/- vancomycin 2nd = tazocin AND vancomycin
Which antibiotics are used to treat HAP caused by:
a. MRSA
b. Pseudomonas
a. MRSA
Vancomycin
b. Pseudomonas
Tazocin OR ciprofloxacin +/- gentamicin
What is the difference between yeasts and moulds?
Yeast = unicellular Moulds = multicellular and has filaments (hyphae)
List three types of mycobacterial complex.
Mycobacterium tuberculosis complex • Mycobacterium tuberculosis • Mycobacterium bovis Mycobacterium avium complex • Mycobacterium avium • Mycobacterium intracellulare Mycobacterium abscessus complex • Mycobacterium abscessus • Mycobacterium massiliense • Mycobacterium bolletii
Describe the morphology of mycobacteria.
Non-motile rod-shaped bacteria
Relatively slow-growing
Cell wall composed of mycolic acids, complex waxes and glycoproteins
Acid-alcohol fast
List three examples of slow-growing non-tuberculous mycobacteria and the diseases that they cause.
Mycobacterium avium intracellulare
• May invade bronchial tree or pre-existing bronchiectasis/cavities
• Disseminated infection in immunocompromised patients
Mycobacterium marinum
• Swimming pool granuloma
Mycobacterium ulcerans
• Skin lesions (e.g. Bairnsdale ulcer, Buruli ulcer)
• Chronic progressive painless ulcer
List three examples of rapid-growing non-tuberculous mycobacteria.
Mycobacterium abscessus
Mycobacterium chelonae
Mycobacterium fortuitum
What are the two types of Mycobacterium leprae infection?
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
List some types of extra-pulmonary TB.
Lymphadenitis (scrofula) – cervical lymph nodes most commonly
Gastrointestinal – due to swallowing of tubercle
Peritoneal – ascitic or adhesive
Genitourinary
Bone and joint – due to haematogenous spread (e.g. Pott’s disease)
Miliary TB
Tuberculous meningitis
What is NAAT and why is it useful for TB?
Nucleic acid amplification test
Allows speciation and the detection of drug resistance mutations
Rapid
List some side-effects of:
a. Rifampicin
b. Isoniazid
c. Pyrazinamide
d. Ethambutol
a. Rifampicin Raised transaminases CYP450 induction Orange secretions b. Isoniazid Peripheral neuropathy (give with pyridoxine) Hepatotoxicity c. Pyrazinamide Hepatotoxicity Hyperuricaemia d. Ethambutol Visual disturbance
What is multi-drug resistant TB?
Resistant to rifampicin and isoniazid
What is extremely drug resistant TB?
Resistant to rifampicin, isoniazid, fluoroquinolones and at least 1 injectable (e.g. amikacin, capreomycin)
Which valvular defect is most common in rheumatic fever?
Mitral stenosis
What is the most common cause of hospital-acquired pneumonia?
Pseudomonas aeruginosa
Which congenital infection is associated with periventricular calcification?
CMV
Why does influenza cause respiratory disease in humans?
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)
Describe the influenza life cycle.
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
Which specific mutation is associated with enabling influenza to cross into humans from birds?
PB2 627K (polymerase protein)
What is the mechanism of action of amantadine?
Targets the M2 ion channel
A single amino acid mutation (S31N) renders the virus resistant
List three examples of neuraminidase inhibitors.
Oseltamivir (Tamiflu) – oral
Zanamivir (Relenza) – inhaled or IV
Peramivir – IV
NOTE: effective if given < 48 hours after infection
List two examples of polymerase inhibitors used to treat influenza.
Favipiravir
Baloxavir
Outline the mechanism of action of aciclovir.
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
What are two 2nd line treatment options for aciclovir-resistant VZV infection?
Foscarnet
Cidofovir
NOTE: they inhibit viral DNA synthesis
HSV encephalitis is a medical emergency. How should it be treated?
IMMEDIATE treatment with IV aciclovir 10 mg/kg TDS without waiting for test results
If confirmed, treat for 21 days
What is HSV meningitis and how should it be treated?
Usually self-limiting
Immunocompromised patients and those who are unwell enough to require hospital admission require treatment
IV aciclovir for 2-3 days followed by oral aciclovir for 10 days
List some indications for treatment of VZV.
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)
In which cells does CMV lie dormant?
Monocytes and dendritic cells
What is a characteristic histological feature of CMV infection?
Owl’s eye inclusions
What is the 1st line treatment option for CMV infection?
Ganciclovir (IV)
How is ganciclovir activated?
Requires activation by viral UL97 kinase enzyme
NOTE: ganciclovir is used in conjunction with IVIG in patients with CMV pneumonitis
What is a major side-effect of ganciclovir?
Bone marrow toxicity
NOTE: therefore, its use is limited in bone marrow transplant patients
What is the mechanism of action of foscarnet?
Non-competitive inhibitors of viral DNA polymerase
NOTE: foscarnet does NOT require activation
Tends to be used in CMV infections if ganciclovir is contraindicated
What is the mechanism of action of cidofovir?
Competitive inhibitors of viral DNA synthesis (nucleotide analogue)
NOTE: does not require activation
What is a major side-effect of foscarnet and cidofovir?
Nephrotoxicity
Cidofovir requires hydration and probenecid
What is the mechanism of action of maribavir?
Inhibits viral kinase
Effective in vitro, currently undergoing clinical trials
What is the mechanism of action of letermovir?
CMV DNA terminase inhibitor
Approved in the USA for CMV prophylaxis in bone marrow transplant patients
What are the roles of haemagglutinin and neuraminidase in the influenza virus?
Haemagglutinin – mediates viral binding and entry into target cell
Neuraminidase – allows release of progeny virus particles from the host cell
What are the 3 indications for use of neuraminidase inhibitors in the community according to NICE?
National surveillance indicates that influenza is circulating
Patient is in a risk group
Within 48 hours of onset of symptoms
What disease states does BK virus cause?
Bone marrow transplant haemorrhagic cystitis
Renal transplants BK nephritis and ureteric stenosis
Outline the treatment of BK haemorrhagic cystitis.
Bladder washouts
Reduce immunosuppression
Cidofovir IV (may consider intravesical)
Outline the treatment of BK nephropathy.
Reduce immunosuppression
IVIG
NOTE: cidofovir cannot be used because it is nephrotoxic
Outline the treatment of adenovirus infection in transplant patients.
Cidofovir IV IVIG Brincidofovir (prodrug of cidofovir currently undergoing clinical trials)
What are most cases of HSV drug resistance caused by?
Mutations in viral thymidine kinase
What are most cases of CMV drug resistance caused by?
Mutations in protein kinase gene UL97
What are the main treatment options for drug resistant HSV and CMV infection?
Foscarnet and cidofovir
What is the herd immunity threshold?
Threshold = 1 – 1/R0
Describe the following types of vaccines:
a. Inactivated
b. Live attenuated
c. Toxoid
d. Subunit
e. Conjugate
f. Heterotypic
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
List examples of the following types of vaccine:
a. Inactivated
b. Live attenuated
c. Toxoid
d. Subunit
e. Conjugate
f. Heterotypic
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
List some contraindications for vaccines.
Previous anaphylactic reactions
Anaphylactic reaction to egg is contraindicated with the influenza vaccine
Immunocompromised and pregnant women should not receive live attenuated vaccines
If acutely unwell on the day of vaccination
DTP is contraindicated if evidence of neurological abnormality
List some examples of serious reactions associated with the following vaccines:
a. DTP
b. Poliovirus
c. Measles
d. Rubella
e. T/DT/Td
f. Hepatitis B
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
Which type of genome do all herpes viruses have?
DNA
What is the most common cause of UTI in young, sexually active women?
Staphylococcus saprophyticus
List some antibiotics that have anti-Pseudomonas activity.
Gentamicin
Ciprofloxacin
Tazocin
What is the most common viral cause of rapidly progressive glomerulonephritis?
Hepatitis B
Which organisms most commonly cause non-bloody diarrhoea and vomiting soon after eating contaminated food?
Bacillus cereus
Staphylococcus aureus
What are the two types of paralysis caused by clostridia?
Botulinum –> flaccid paralysis
Tetani –> spastic paralysis
What are the possible outcomes for neonates with congenital toxoplasmosis?
Asymptomatic (60%) at birth but go on to develop long-term sequelae such as deafness, low IQ and microcephaly Symptomatic (40%) at birth • Choroidoretinitis • Microcephaly/hydrocephalus • Intracranial calcifications • Seizures • Hepatosplenomegaly/jaundice
What is the triad of features in congenital rubella syndrome?
Cataracts
Congenital heart disease (PDA is most common)
Deafness
Other features: microphthalmia, glaucoma, retinopathy, ASD/VSD, microcephaly, meningoencephalopathy, developmental delay
How if Chlamydia trachomatis transmitted to the neonate and what disease does it cause in the neonate?
During delivery
Causes neonatal conjunctivitis (ophthalmia neonatorum) or pneumonia
NOTE: it is treated with erythromycin
Which mycoplasma species can cause neonatal infection?
Mycoplasma hominis
Ureaplasma urealyticum
What are the three main organisms that cause early-onset infection?
Group B Streptococcus
E. coli
Listeria monocytogenes
What type of bacterium is Group B Streptococcus?
Gram-positive coccus
Catalase negative
Beta haemolytic
What type of organism is Listeria monocytogenes and what disease can it cause?
Gram-positive rods
Causes sepsis in the mother and the newborn
Which antibiotics are commonly used to treat early-onset sepsis?
Benzylpenicillin + gentamicin
What are the main causes of late-onset sepsis?
Coagulase negative staphylococci (e.g. S. epidermidis)
GBS
E. coli
Listeria monocytogenes
S. aureus
Enterococcus sp.
Gram-negatives (e.g. Klebsiella, Enterobacter, Pseudomonas)
Outline the treatment of late-onset sepsis.
Treat early with antibiotics
Guidelines differ
Example antibiotic regimen: 1st line = cefotaxime + vancomycin; 2nd line = meropenem
What is the main bacterial cause of meningitis at the moment?
Meningitis B
What type of organism is Streptococcus pneumoniae?
Gram-positive diplococcus
Alpha haemolytic
What type of organism is Haemophilus influenzae?
Gram-negative cocco-bacilli
What is the most common cause of death in:
a. Postnatal children (1-59 months)
b. Neonates
a. Postnatal children (1-59 months) Pneumonia Followed by congenital anomalies b. Neonates Prematurity Followed by intra-partum complications
Which children are mainly affected by Mycoplasma pneumoniae?
Older children (> 4 years)
List some extra-pulmonary manifestations of Mycoplasma pneumoniae.
Haemolysis – IgM antibodies to I antigen on erythrocytes, cold agglutinins
Neurological – encephalitis, aseptic meningitis, peripheral neuropathy, transverse myelitis
Polyarthralgia
Otitis media
Bullous myringitis (vesicles on the tympanic membrane – pathognomonic of Mycoplasma)
Erythema multiforme
List three examples of:
a. Yeast
b. Moulds
a. Yeast Candida Cryptococcus Histoplasma (dimorphic) b. Moulds Aspergillus Dermatophytes Agents of mucormycosis
List some patient groups that are at risk of invasive Candida infection.
VLBW infants
Immunocompromised
Patients on ITU (especially if they have lines in)
Patients receiving TPN
Immunocompetent patients who have had antibiotic treatment
List some agents that can cause candidiasis.
Candida albicans (MOST COMMON)
Candida glabrata
Candida krusei
Candida tropicalis
Describe a screening test for candidiasis.
Candida albicans forms a germ tube
Can be identified by microscopy
What does generalised candidiasis in babies usually occur secondary to?
Seborrhoeic dermatitis
What type of agar is needed for culturing Candida?
Sabouraud agar – impregnated with antibiotics to prevent bacteria from outcompeting the fungi
Outline the management of candidiasis.
At least 2 weeks of antifungals after the last negative culture
Echo and fundoscopy to look for endocarditis/endophthalmitis
Echinocandins – empirical for non-albicans infections
Fluconazole – empirical for Candida albicans
What is the treatment of choice for Cryptococcus infection?
Ambisome (amphotericin B)
NOTE: it is inherently resistant to echinocandins
Describe the appearance of Cryptococcus under the microscope.
Distinct capsule around the yeast
India ink can be used to stain
NOTE: the capsule is not always present
Why might a lumbar puncture be negative in cryptococcal meningitis?
Cryptococcal meningitis can cause hydrocephalus which prevents the circulation of CSF meaning that the sample taken at LP may not have been exposed to CSF within other parts of the ventricular system
Outline the treatment options for Cryptococcus infection.
3 weeks amphotericin B (ambisome) +/- flucytosine
Repeat LP for pressure measurement
Secondary suppression – fluconazole
List the aetiological agents that can cause Aspergillus infection.
Aspergillus fumigatus Aspergillus flavus Aspergillus niger Aspergillus niduland Aspergillus terreus
List some investigations used in the diagnosis of Aspergillus infection.
Blood test Serology (check IgE for allergic response (e.g. ABPA)) • Antigen detection (galactomannan) • Also detected in BAL PCR Histology Culture
What is the mainstay of treatment for aspergillosis?
Amphotericin for at least 6 weeks
Other options: voriconazole, caspofungin, itraconazole
What is tinea pedis caused by?
Tricophyton rubrum (MOST COMMON) Tricophyton interdigitale Epidermophyton floccosum (can also cause tinea cruris)
What is pityriasis versicolor caused by?
Malassezia furfur
NOTE: it has a spaghetti and meatballs appearance on microscopy
Which groups of patients are affected by mucormycosis?
Immunocompromised patients
Patients with poorly controlled diabetes
What is the characteristic clinical manifestation of mucormycosis?
Cellulitis of the orbit and face which progresses with discharge and black pus from the palate and nose
NOTE: black eschars may be seen as the fungus destroys tissues
What is the term used to describe invasion of the brain by mucormycosis?
Rhinocerebral mucormycosis
List three aetiological agents that can cause mucormycosis.
Rhizopum spp.
Rhizomucor spp.
Mucor spp.
List antifungals that target:
a. Cell membrane
b. DNA/RNA synthesis
c. Cell wall
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
What is the mechanism of action of azoles?
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
List examples of the following types of azoles along with their usual indications:
a. Water-soluble triazoles
b. Lipophilic triazoles
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
List some examples of echinocandins.
Caspofungin
Micafungin
Anidulafungin
What is the mechanism of action of echinocandins?
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
Which fungi are echinocandins active against?
Candida species
Aspergillus species (NOT other moulds)
IMPORTANT: it has NO coverage for Cryptococcus
How is amphotericin B produced?
Fermentation product of Streptomyces nodusus
Describe the mechanism of action of amphotericin B.
Binds to ergosterol in the fungal cell membrane and creates transmembrane channels leading to electrolyte leakage
This leads to fungal cell death
Amphotericin B is active against most fungi except…
Aspergillus terreus
Scedosporium spp.
What is the main side-effect of amphotericin B? Describe the mechanism of this toxicity.
Nephrotoxicity
Renovascular – decrease in renal blood flow leads to reduced GFR (azotaemia)
Tubular – distal tubular ischaemia, wasting of sodium, potassium and magnesium
Describe the mechanism of action of flucytosine.
Inhibits DNA synthesis (pyrimidine analogue)
What are some mechanisms of resistance to flucytosine?
Decreased uptake (permease activity) Altered 5-FC metabolism
Which fungi are flucytosine active against?
Candidiasis
Cryptococcosis
Which fungi are flucytosine active against?
Candidiasis
Cryptococcosis
Describe the mechanisms of teratogenicity of rubella.
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
Describe some tests that are used in the diagnosis of rubella.
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
What is the role of pre-natal diagnosis of rubella?
All cases of symptomatic rubella infection in the 1st trimester should be considered for termination of pregnancy without prenatal diagnosis
What is the definition of congenital CMV infection?
Detection of CMV from bodily fluids (normally urine and saliva) or tissues within the first 3 weeks of life
NOTE: it is the MOST COMMON congenital viral infection
What is the term used to describe congenital changes that occur as a result of CMV infection? List some features.
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
Outline some tests used in the diagnosis of CMV infection.
Virus detection – cell culture, detection of early antigen fluorescent foci (DEAFF), CMV DNA (PCR)
Serology – IgG seroconversion, IgG avidity, IgM
How is congenital CMV infection treated?
There is NO vaccine
Congenital CMV with significant organ disease
• Valganciclovir or ganciclovir for 6 months
• Audiology follow-up until age 6 years
• Ophthalmology review
Outline the manifestations of neonatal HSV disease.
Skin, eyes and mouth (SEM) disease
CNS disease with or without SEM
Disseminated infection involving multiple organs (high mortality)
Describe the clinical presentation of intrauterine HSV infection.
Neurological – microcephaly, encephalomalacia, intracranial calcification
Cutaneous – scarring, active lesions
Ophthlamologic – microophthalmia, optic atrophy, chorioretinitis
Describe the treatment of neonatal HSV infection.
High-dose IV aciclovir (60 mg/kg/day) in three divided doses
For 21 days minimum in disseminated disease (repeat LP and CSF PCR until PCR-negative)
For 14 days minimum in SEM disease
Monitor neutrophil count
List the main features of congenital varicella syndrome.
LBW Cutaneous scarring Limb hypoplasia Microcephaly Chorioretinitis Cataracts NOTE: risk is highest at 13-20 weeks
Describe the manifestations of neonatal varicella infection.
Mild course
Disseminated skin lesions
Visceral infection
Pneumonia
List some complications of measles.
Opportunistic bacterial infection (otitis media, pneumonia, bronchitis)
Encephalitis
Subacute sclerosing panencephalitis
• Tends to occur 6-15 years after measles infection
• Present with delays motor skills and behavioural problems
What are the risks of measles in pregnancy?
Foetal loss (miscarriage, intrauterine death)
Preterm delivery
Increased maternal morbidity
IMPORTANT: NO congenital abnormalities to the foetus
How should pregnant women who have been in contact with suspected/confirmed measles be treated?
Measles immunoglobulin attenuates the illness if given within 6 days of exposure
What type of virus is parvovirus B19?
DNA virus
Parvoviridae family
NOTE: MMR are all RNA viruses
What does the virus require in order to infect red cell precursors?
P blood antigen receptor (globoside)
Describe the pathophysiology of congenital parvovirus B19 infection.
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
Describe how maternal parvovirus B19 infection can be diagnosed.
PCR – DNA amplification
Serology – parvovirus IgG seroconversion and IgM
Foetal infection – same tests
What are some consequences of Zika virus infection in pregnancy.
Miscarriage Stillbirth Congenital zika syndrome • Severe microcephaly • Decreased brain tissue • Seizures • Retinopathy/deafness • Talipes • Hypertonia
Give two examples of glycopeptides.
Vancomycin
Tiecoplanin
Outline the mechanism of action of beta-lactam antibiotics.
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)
For each of the following antibiotics, describe their coverage and mechanisms of resistance:
a. Penicillin
b. Amoxicillin
c. Flucloxacillin
d. Piperacillin
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
What is a disadvantageous association of ceftriaxone?
Associated with C. difficile infection
What is a benefit of ceftazidime?
Good anti-Pseudomonas cover
List examples of bacteria that have shown carbapenem resistance.
Acinetobacter
Klebsiella
Outline the key features of beta-lactam antibiotics.
Relatively non-toxic
Renally excreted (reduced dose in renal impairment)
Short half-life
Will not cross an intact blood-brain barrier (may cross inflamed meninges in meningitis)
Cross allergenic (penicillins have 5-10% cross-reactivity with cephalosporins and carbapenems)
What are glycopeptides often used to treat?
Serious MRSA infections
C. difficile infections (oral vancomycin)
What is a major side-effect of glycopeptides?
Nephrotoxic
Monitor blood levels to prevent accumulation
Outline the mechanism of action of glycopeptides.
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)
List some classes of antibiotics that work by inhibiting protein synthesis.
Aminoglycosides Tetracyclines Macrolides Lincosamides (e.g. clindamycin) Streptogramins (e.g. Synercid) Chloramphenicol Oxazolidinones (e.g. linezolid)
Outline the mechanism of action of aminoglycosides.
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
What are some major side-effects of aminoglycosides?
Ototoxic and nephrotoxic
Which aminoglycosides are particularly active against Pseudomonas aeruginosa?
Gentamicin
Tobramycin
Which type of bacteria do aminoglycosides have no activity against?
Anaerobes
List some examples of aminoglycosides.
Gentamicin Tobramycin Amikacin Neomycin Paromomycin
Which environmental feature will inhibit the activity of aminoglycosides?
Inhibited by low pH so are not very effective in abscesses
Which class of antibiotics are particularly effective against intracellular bacteria (e.g. chlamydia, rickettsia, mycoplasma)?
Tetracyclines
Newer quinolones are also effective
List some examples of tetracyclines.
Tetracycline
Doxycycline
Oxytetracycline
Which new tetracycline has extended the spectrum of tetracyclines?
Tigacycline
Before this, there was widespread resistance amongst Gram-negatives
Which groups of patients should not receive tetracyclines?
Children and pregnant women
Because it can deposit in bone and cause discoloration of growing teeth
NOTE: a well known side-effect is a light-sensitive rash
Outline the mechanism of action of tetracyclines.
Binds to the ribosomal 30S subunit and prevents the binding of aminoacyl-tRNA to the ribosomal acceptor site, thereby inhibiting protein synthesis
What are macrolides mainly used for?
Mild staphylococcal and streptococcal infections in penicillin-allergic patients
Also active against Campylobacter, Legionella and Pneumophila
Outline the mechanism of action of macrolides.
Binds to the 50S ribosomal subunit and interferes with translation
Also stimulates the dissociation of peptidyl-tRNA
What are two major risks of taking chloramphenicol?
Aplastic anaemia
Grey baby syndrome – neonates have reduced ability to metabolise the drug
Outline the mechanism of action of chloramphenicol.
Binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation
Outline the mechanism of action of oxazolidinones.
Binds to the 23S components of the 50S subunit to prevent the formation of a functional 70S initiation complex (needed for translation)
Which organisms are oxazolidinones active against?
Gram-positives (including MRSA and VRE)
Not active against Gram-negatives
What are some disadvantages of oxazolidinones?
Expensive
May cause thrombocytopaenia and optic neuritis
List two groups of antibiotics that inhibit DNA synthesis.
Quinolones
Nitroimidazoles
List 3 examples of quinolones.
Ciprofloxacin
Moxifloxacin
Levofloxacin
List 2 examples of nitroimidazoles.
Metronidazole
Tinidazole
Outline the mechanism of action of quinolones.
Acts on the alpha-subunit of DNA gyrase predominantly with other actions
Describe the activity of quinolones.
Broad antibacterial activity, especially against Gram-negatives, including Pseudomonas aeruginosa
NOTE: newer agents increased activity against Gram-negatives and intracellular organisms
Outline the mechanism of action of nitroimidazoles.
Under anaerobic conditions, an active intermediate is formed, which causes DNA strand breakage
Describe the activity of nitroimidazoles.
Active against anaerobic bacteria and protozoa (e.g. Giardia)
Outline the mechanism of action of rifampicin.
Inhibits RNA synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation
Describe the activity of rifampicin.
Mainly Mycobacteria and Chlamydiae
Why should rifampicin never be used alone?
Resistance develops rapidly due to chromosomal mutation (single amino acid change in beta-subunit of RNA polymerase)
Name two cell membrane toxins.
Daptomycin
Colistin
Describe the activity of daptomycin.
Gram-positives
Likely to be used in treating MRSA and VRE
NOTE: it is a cyclic lipopeptide
Describe the activity of colistin.
Active against Gram-negatives including Pseudomonas aeruginosa, Acinetobacter baumanii and Klebsiella pneumoniae
NOTE: it is a polymyxin
Name two families of antibiotics that work by inhibiting folate metabolism.
Sulphonamides (sulfamethoxazole)
Diaminopyrimidines (trimethoprim)
List some mechanisms of antibiotic resistance.
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
Which bacteria produce beta-lactamases?
S. aureus and Gram-negative bacilli (coliforms)
NOTE: this is not the mechanism of resistance in pneumococcus and MRSA
Describe how MRSA uses ‘altered targets’ as a mechanism of resistance.
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
Describe the mechanism of resistance in Streptococcus pyogenes.
Results from acquisition of a series of stepwise mutations in PBP genes
Lower level resistance can be overcome by increasing the dose
What are AmpC beta-lactamases?
Breakdown penicillins and cephalosporins but are not inhibited by clavulanic acid
Describe the mechanism of resistance to macrolides.
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
Name two methods of rapid antigen detection.
PCR
Immunofluorescence
Describe the type I pattern of antibiotic activity. Give an example of an antibiotic of this type.
Concentration-dependent killing
Peak above the MIC (Cmax) is the most important parameter
Example: aminoglycosides
These drugs tend to be given as one big dose
The benefits of achieving a higher Cmax must be balanced with the increased toxicity
Trough concentration should also be measured to ensure that the drug is being eliminated (this determines the frequency of drug administration)
Describe the type II pattern of antibiotic activity. Give an example of an antibiotic of this type.
Time-dependent killing
Time spent above the MIC is the most important factor
Example: penicillins
Therefore, penicillins need to be given frequently
Describe the type III pattern of antibiotic activity. Give an example of an antibiotic of this type.
Concentration and time-dependent
AUC above the MIC is the most important factor
Example: vancomycin
NOTE: infusions may be used to maintain an AUC above the MIC
How should invasive group A streptococcal infection be treated?
Aggressive and early debridement
Early use of antibiotics (e.g. clindamycin)
Use of IVIG
How is meningitis in babies < 3 months treated?
Cefotaxime + amoxicillin
NOTE: ceftriaxone is NOT used in neonates because it displaces bilirubin from albumin and causes biliary sludging
List some primary causes of immune compromise.
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
List some iatrogenic causes of immunosuppression in order of increasing risk of opportunistic viral infection.
DMARDs and steroids (LOWEST RISK) Cytotoxic chemotherapy Monoclonal antibodies Solid organ transplant Advanced HIV Allogeneic stem cell transplant (HIGHEST RISK)
List some diseases that it is important to monitor for in post-transplant patients.
CMV monitoring and prophylaxis
EBV monitoring
Adenovirus monitoring (in paediatric BMT)
HSV prophylaxis if indicated
List the sites of latent infection of:
a. VZV
b. CMV
c. EBV
a. VZV Dorsal root ganglion b. CMV Monocytes c. EBV B cells
In bone marrow transplant patients, describe the timescale in which the herpes infections tend to occur.
HSV, HHV6 and HHV7 tend to occur < 1 month after transplant
CMV, VZV and EBV tend to reactivate later
List some manifestations of VZV infection.
Skin lesions Pneumonitis Encephalitis Hepatitis Purpura fulminans (neonates) Acute retinal necrosis VZV-associated vasculopathy
What is the pathological hallmark of CMV infection?
Owl’s eye appearance of lung pneumocytes due to the presence of inclusion bodies
How is the risk of reactivation of CMV different in solid organ transplantation compared to bone marrow transplantation?
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
Which other diseases is HHV8 associated with?
Primary effusion lymphoma
Multicentric Castleman’s disease
What deadly condition is JC virus associated with?
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
Which specific medication is associated with an increased risk of PML?
Natalizumab – monoclonal antibody used in the treatment of multiple sclerosis
What can BK virus cause?
BK cystitis (post-stem cell transplant) BK nephropathy (post-renal transplant) NOTE: can be treated by reducing immunosuppression
List some manifestations of adenovirus infection in bone marrow transplant patients.
Fever
Encephalitis
Pneumonitis
Colitis
How is parvovirus B19 infection in the immunocompromised treated?
IVIG
Blood transfusion may be required to correct the anaemia
Which treatments particularly increase the risk of hepatitis B infection?
B-cell depleting therapies (e.g. rituximab)
This can be prevented by using nucleoside analogue (e.g. tenofovir) prophylaxis
What are the three main types of worms? List some examples of each.
Cestodes (tape worms) • Pork/beef/fish tapeworms • Hydatid disease Trematodes (flukes) • Schistosomiasis Nematodes (roundworms) • Hookworms • Ascarids • Strongyloides
What are the two types of pork and beef tapeworms?
Taenia solium – pork (can invade human tissues causing cysticercosis)
Taenia saginata – beef
Outline the lifecycle of schistosomiasis.
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
How is schistosomiasis diagnosed?
Microscopy • Urine: S. haematobium • Stools: S. mansoni, S. japonicum Serology Biopsy Response to treatment
What are the five main soil-transmitted helminths?
Ascaris lumbricoides Strongyloides stercoralis Trichuris trichiura Enterobius vermicularis Hookworm NOTE: they are very well adapted to humans so cause little disease
Outline the lifecycle of Strongyloides.
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
How is Strongyloides treated?
Ivermectin
How are the nematode infections that cause filariasis spread?
Blackflies and mosquitoes
Outline the classification of filariasis.
Based on location Lymphatic filariasis • Wucheria • Brugia Subcutaneous filariasis • Onchocerciasis • Mansonella • Loa Loa Serous cavity filariasis • Mansonella • Dirofilaria NOTE: adult worms are only found in humans
What causes damage in filariasis?
Adults: lymphatic filariasis (scrotal swellings, elephantiasis) and oncho nodules
Microfilariae: onchocerciasis (depigmentation, river blindness)
What is myiasis?
Parasitisation of human flesh by fly larvae
Outline the components of a reasonable parasite screen.
Serology: Strongyloides, Schistosoma, filaria
Stool microscopy
How is the acquisition of pig tapeworm different from the acquisition of cysticercosis?
Ingesting cysts from undercooked pork will lead to the development of adult tapeworms in the human GI tract
Ingesting tapeworm eggs will lead to cysticercosis
NOTE: humans and pigs are immunologically very similar
Outline the management of cysticercosis.
Anticonvulsants
Advice not to drive
Ventriculo-peritoneal shunt if hydrocephalus
Cestocidal drugs (e.g. praziquantel, albendazole)
This MUST be given with steroids to reduce inflammation around dying cysts
How long does TB take to divide?
18-24 hours
List some risk factors for TB.
Malnutrition (most common) HIV (very serious risk factor) Poverty Underweight Past TB
List some clinical features of severe malaria.
High parasitaemia Altered consciousness ARDS Circulatory collapse Metabolic acidosis Renal failure Hepatic failure Coagulopathy Severe anaemia Hypoglycaema
Which stains are used for malaria?
Giemsa
Field’s
Outline the treatment options for non-falciparum malaria.
Chloroquine – 3 days
Primaquine – 30 mg for 14 days
What must you do before giving someone primaquine?
Screen for G6PD deficiency as primaquine can cause extensive haemolysis
Outline the treatment options for mild falciparum malaria.
Oral malarone (atovaquone and proguanil) Artemisinin combination therapy (ACT) Oral quinine (RARELY used)
Outline the treatment of severe falciparum malaria.
ABCDE approach Correct hypoglycaemia Cautious hydration Organ support if necessary IV artesunate Daily parasitaemia monitoring Follow on with oral antimalarials
Why is quinine not used in this situation?
Extensive side effects:
• Cinchonism: tinnitus, dizziness, nausea and vomiting
• Arrhythmias
• Hyperinsulinaemia
Outline the clinical features of dengue.
Fever Headache (retro-orbital pain) Myalgia Erythrodermic rash Bleeding Hepatitis Severe: encephalitis, myocarditis
Which tropical virus is similar to dengue? What is a key difference?
Chikungunya
Arthralgia is more severe
What is the term used to describe a high temperature with a relatively normal heart rate? List some causes.
Sphygmothermic dissociation
Causes: typhoid, yellow fever, brucellosis, tularaemia
What type of organism is Salmonella typhi?
Gram-negative rod
Outline the clinical features of typhoid.
High prolonged fever Headache Rose spots Constipation Dry cough Hepatosplenomegaly
What is the incubation period of typhoid?
7-18 days
Outline the treatment of typhoid.
1st line: ciprofloxacin
Ceftriaxone 2 g IV OD
Azithromycin PO 500 mg BD 7 days
List some investigations for mononucleosis.
Monospot
IgM EBV/CMV
NOTE: always consider HIV
Which antibiotic should be given as prophylaxis in close contacts of a patient with meningococcal meningitis?
Ciprofloxacin (or rifampicin)
Which organism can cause bacterial endocarditis after a colonoscopy?
Streptococcus bovis
How is latent TB treated?
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
What type of bacterium is Moraxella catarrhalis?
Gram-negative coccus
Associated with smoking
What type of bacterium is Klebsiella pneumoniae?
Gram-negative rod (enterobacter)
NOTE: more common in alcoholics and the elderly
Which bacteria tend to cause respiratory infection in cystic fibrosis patients?
Pseudomonas aeruginosa
Burkholderia cepacia
List some causes of painful genital ulcers.
Herpes
Chancroid
List some causes of painless genital ulcers.
Syphilis (also causes snail track ulcer in the mouth)
Lymphogranuloma venereum (LGV)
Granuloma inguinale
How is gonorrhoea treated?
IM Ceftriaxone 250 mg single dose
NOTE: if resistant - IM spectinomycin 2 g single dose
Which serovars of chlamydia cause genital chlamydia?
D-K
NOTE: A, B and C cause trachoma (infection of the eyes that can lead to blindness)
How is chlamydia diagnosed?
NAAT
NOTE: chlamydia cannot be grown on agar, it needs to be grown on cell culture (as it is an obligate intracellular bacterium)
How is chlamydia treated?
Azithromycin 1 g stat
Doxycycline 100 mg BD for 7 days
What causes lymphogranuloma venereum?
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)
Which investigations are used for syphilis?
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
Outline the stages of syphilis.
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
How is syphilis treated?
IM benzathine penicillin (doxycycline if allergic)
What causes chancroid?
Haemophilus ducreyi (Gram-negative coccobacillus) Grows on chocolate agar
What causes granuloma inguinale?
Donovanosis - Klebsiella granulomatis (Gram-negative bacillus)
Causes large expanding ulcers with a beefy red appearance
What might be seen on microscopy of bacterial vaginosis?
Clue cells
What is herpangina?
Painful mouth ulcers caused by Coxsackie A virus
What feature may be seen on blood film analysis of P. vivax and P. ovale?
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
What is Mollaret’s meningitis?
Benign recurrent aseptic meningitis usually due to HSV-2
NOTE: unlike most herpes simplex encephalitis which is caused by HSV-1
What is Herpes gladiatorum?
Scrum pox - painful blisters, inguinal lymphadenopathy, rugby players
Which cell type can be seen in cytological analysis of scrapings from herpes viruses?
Tzanck cells - acanthocytic cells found in HSV, VZV and CMV
What are the different types of GI disease that can be caused by E. coli?
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
What does Yersinia enterocolitis cause?
Enterocolitis, mesenteric adenitis with necrotising granulomas associated with reactive arthritis and erythema nodosum
What is leptospirosis?
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
How does anthrax manifest?
Caused by Bacillus anthracis
Cutaneous - painless round black lesions with a rim of oedema
Pulmonary (Woolsorters disease) - massive lymphadenopathy, mediastinal haemorrhage, pleural effusion
What is Q fever?
Caused by Coxiella burnetii
From cattle/sheep
Fever, dry cough, fatigue, diarrhoea (like atypical pneumonia)
What are the different types of Leishmania?
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
What is the preferred first line treatment choice for Hepatitis B?
Entecavir + peginterferon alpha 2a + tenofovir
NOTE: treatment usually initiated if HBV DNA > 2000 iU/mL, moderate-severe histology or raised aminotransferases
What are the risks of influenza in pregnancy?
Stillbirth Preterm delivery Severe influenza NO congenital abnormalities Pregnant women should receive the vaccine
What are the most common causative organisms in aseptic meningitis?
Coxsackie group B viruses
Echoviruses
NOTE: babies < 1 year are susceptible for aseptic meningitis
Which bacterium is particularly associated with causing encephalitis?
Listeria monocytogenes
List some reportable GI infections.
Campylobacter Salmonella Shigella Escherichia coli O157 Listeria
Describe the mechanism by which Vibrio cholerae causes secretory diarrhoea.
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
What type of toxins does B. cereus produce?
Heat stable emetic toxin
Heat labile diarrhoeal toxin
List three species of Salmonella.
Salmonella typhi (and paratyphi)
Salmonella enteritidis
Salmonella choleraesuis
Which subset of patients are at increased risk of Salmonella bacteraemia?
Sickle cell patients
How does Shigella infection manifest?
Dysentery – severe diarrhoea with blood and mucus in the faeces
NOTE: Shigella produces shiga toxin
NOTE: avoid antibiotics when treating Shigella
How is Campylobacter infection treated?
Only treated if immunocompromised
Erythromycin/clarithromycin or ciprofloxacin
What are some complications of Campylobacter infection?
Guillain-Barre syndrome
Reactive arthritis
How is Giardia infection diagnosed and treated?
Stool microscopy
ELISA
String test
Treatment: metronidazole
Which bacteria are all stool samples tested for?
Salmonella
Shigella
E. coli O157
If > 65 years, C. difficile is also checked
Which C. difficile ribotype caused a severe outbreak in June 2005?
Ribotype 027
What are the actions of the two toxins produced by C. difficile?
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
Describe the clinical features of sporadic CJD.
Rapid dementia Myoclonus Cortical blindness Akinetic mutism LMN signs NOTE: usually in older people (> 65)
Describe the clinical features of vCJD.
Younger age of onset (20s)
Psychiatric onset (dysphoria, anxiety, delusions, hallucinations)
Followed by neurological symptoms (peripheral sensory symptoms, ataxia, myoclonus, chorea, dementia)
NOTE: characteristic MRI feature is pulvinar sign (high intensity in the putamen)
What are some alternative diagnoses for someone presenting with features suggestive of prion disease?
Spinocerebellar ataxia
Huntington’s disease
Which virulence factor allows S. saprophyticus to stick to the urinary tract epithelium?
P-fimbriae
NOTE: S. saprophyticus causes infection in young women
In which patients do Candida UTIs tend to occur?
Patients with indwelling catheters
Treated by removal of catheter only (unless renal transplant)
Which bacterium is associated with causing infection on prosthetic heart valves?
Staphylococcus epidermidis
Which antiviral can be used to prevent RSV infection in at risk infants?
Ribavirin
NOTE: ribavirin is a guanosine nucleoside analogue
What is the mechanism of action of zidovudine?
Nucleoside reverse transcriptase inhibitor (NRTI)
Which virus is associated with causing acute necrotising encephalitis?
HSV1
This is the MOST COMMON cause of encephalitis
What are the three classes of herpes viruses?
Alpha: neurotropic
Beta: epitheliotropic
Gamma: lymphotropic
What causes oral hairy leukoplakia and which patient subgroup is associated with this condition?
EBV
Immunocompromised (e.g. HIV or IVDU)
Which naturally occurring cytokine can inhibit HIV fusion with CD4 cells?
MIP-1-alpha
Describe the main clinical features of giardiasis.
Severe flatulence
Bloating
Explosive diarrhoea
Where does cryptococcus neoformans come from?
Pigeon droppings and pigeon nests
NOTE: histoplasmosis also comes from bird droppings
What are the typical symptoms of rubella?
Macular rash beginning behind the ears
Lymphadenopathy
Joint pain
Fever
List some causes of ring-enhancing brain lesions.
Abscess
Tuberculoma
Toxoplasmosis
CNS lymphoma
What is the most common cause of UTI in catheterised men?
E. coli
Describe the typical presentation of bacterial prostatitis.
Fever and rigors
Lower back pain
Dysuria
Describe the microbiological appearance of Enterococcus.
Gram-positive cocci in chains (or pairs)
Describe the microbiological appearance of Pseudomonas.
Gram-negative bacilli
Produce green pigment
Oxidase positive
List some examples of Gram-positive bacilli.
Bacillus cereus, bacillus anthracis Clostridia Corynebacterium diphtheriae Listeria Actinomyces
List some examples of Gram-negative bacilli.
E. coli Klebsiella Proteus Salmonella Shigella Yersinia Pseudomonas Bordatella pertussis Haemophilus influenzae Legionella
List some examples of Gram-negative comma-shaped or curved bacteria.
Vibrio
Campylobacter
Helicobacter
List some examples of spiral-shaped bacteria (spirochete).
Treponema pallidum
Borrelia burgdorferi
Leptospira interrogans
What CXR feature might be seen in invasive aspergillosis?
Halo sign
How is a surgical site infection caused by MRSA treated?
IV linezolid
Which investigation should be requested if the initial tests for PUO fail to establish a diagnosis?
PET-CT
List some organisms that cause HAP.
Enterobacteriaciae (MOST COMMON – e.g. E. coli, K. pneumoniae) Staphylococcus aureus Pseudomonas Haemophilus influenzae Acinetobacter baumanii Fungi (e.g. Candida)
What counts as a positive result on the Mantoux Test?
> 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
How is post-transplant lymphoproliferative disease treated?
Reduce immunosuppression
Rituximab (anti-CD20)
Which score is used to determine if a patient has sepsis?
Q-SOFA
Altered Mental Status (GCS < 15)
Tachypnoea (22 or more)
Hypotension (< 100 mm Hg)
Score of 2 or more is high risk
What are Amsel’s criteria for diagnosing BV?
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
Which antibiotic should be given in a case of human or animal bite?
Co-amoxiclav
Which antibiotics are used to treat the following GI infections:
Campylobacter
Salmonella
Shigella
Campylobacter = clarithromycin or erythromycin
Salmonella or Shigella = ciprofloxacin
Give one example of each of the following types of HIV drugs: NRTI NNRTI Protease Inhibitor Integrase Inhibitor
NRTI: zidovudine
NNRTI: nevirapine
Protease Inhibitor: saquinavir
Integrase Inhibitor: raltegravir
State the antibiotic regimens used to treat subacute and acute bacterial endocarditis.
Subacute: Benzylpenicillin + gentamicin; or vancomycin for 4 weeks
Acute: Flucloxacillin for MSSA, rifampicin + vancomycin + gentamicin for MRSA.
Name three types of brucella.
Brucella abortus (cows) Brucella melitensis (goats) Brucella suis (pigs)
Which respiratory pathogen commonly causes pneumonia in smokers with COPD?
Haemophilus influenzae
NOTE: Moraxella catarrhalis is also associated with smoking
When does pneumonia caused by S. aureus tend to occur?
After a recent viral infection (influenza)
Outline the management of an infective exacerbation of COPD.
Mild: doxycycline/amoxicillin/clarithromycin + inhalers + prednisolone
Mod/Severe: IV antibiotics + nebulisers + hydrocortisone
List diarrhoeal diseases that have the following incubation periods: < 6 hours 12-48 hours 48-72 hours > 1 week
< 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
Which emerging fungal infection causes invasive hospital-acquired infections?
Candida auris
Particularly in immunocompromised patients with indwelling catheters
How can Aspergillus flavus cause hepatocellular cancer?
Aflatoxin A1
What is a fungal cell wall made up of?
Glucan
Chitin
List some investigations used for PUO.
Urine (dipstick, antigen, microscopy) Bloods (FBC, eosinophils, ESR, 3 x blood culture, thick and thin blood films) HIV test Autoantibody screen CXR CT-TAP
How is infective endocarditis treated?
S. viridans: benzylpenicillin + gentamicin
S. aureus: flucloxacillin
MRSA: vancomycin + gentamicin
May require removal of the valve
What is the most common cause of fever in the returning traveller?
Malaria
Describe the clinical presentation of lyme disease.
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
Which medications are used to treat hepatitis C?
Protease inhibitor (e.g. sofosbuvir + daclatasvir) with or without ribavirin is the mainstay
NOTE: interferon-based treatments are no longer used
What is the technical term for dog tapeworm?
Echinococcus granulosus
List the bacteria that fall under alpha, beta and gamma haemolytic streptococci.
Alpha: S. pneumoniae, S. viridans
Beta: S. pyogenes, S. epidermidis
Gamma: Enterococcus (faecalis, faecum)
NOTE: beta haemolytic streptococci are further divided into Lancefield groups
Which bacteria is optochin sensitivity useful to differentiate between?
Optochin Sensitive: S. pneumoniae
Optochin Resistant: S. viridans (and other alpha haemolytic streptococci)
List the organisms that are oxidase-positive.
Pseudomonas Neisseria Campylobacter Helicobacter Moraxella Vibrio Legionella
Mnemonic: PuNCH Me Very Lightly
Which organisms cause the following types of leishmaniasis:
Visceral
Cutaneous
Mucocutaneous
Visceral: L. donovani, L. infantu, L. chagasi
Cutaneous (most common): L. major, L. tropica
Mucocutaneous: L. braziliensis
What are the main clinical features of trypanosomiasis and what are the two main forms?
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
Briefly describe the lifecycle of plasmodium.
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
What is the best diagnostic test for hepatitis C?
HCV RNA
NOTE: chronic infection is defined as the persistence of HCV RNA after 6 months
How long is the HIV incubation period?
3-12 weeks
Therefore, an HIV test should only be performed 3 months after exposure
What are the first and second line treatment options for PCP?
1st line: co-trimoxazole
2nd line: clindamycin and primaquine
Which viral and fungal/parasite infections are T and B cell deficiencies associated with?
T cells - Viruses: CMV, EBV, VZV - Fungi/Parasites: Candida, PCP B cells - Viruses: enteroviral encephalitis - Fungi/Parasites: Giardia
What is a ‘complicated’ UTI?
Infection in a UTI with structural or functional abnormalities (including indwelling catheters and calculi) Includes any UTI in: - Men - Pregnant Women - Children - Hospitalised patients
How would you manage a patient with leucocyte positive, nitrite negative urine?
Treat if severe symptoms and send urine culture
When should patients with a UTI have urine sent for microscopy, culture and sensitivities?
Pregnancy, children or men
Suspected pyelonephritis
Catheterised patients
Failed antibiotic treatment (resistance)
Abnormalities of the genitourinary tract
Renal impairment
What is the antibiotic regimen of choice for an uncomplicated UTI in a woman?
Nitrofurantoin or Cephalexin
What is the antibiotic regimen of choice for a UTI in a pregnant woman?
1st line: nitrofurantoin (avoid at term)
2nd line: cefalexin or co-amoxiclav
What is the antibiotic regimen of choice for a UTI in a man?
Cefalexin or ciprofloxacin
Chronic prostatitis: ciprofloxacin 500 mg BD PO for 4-6 weeks
What is the antibiotic regimen of choice for pyelonephritis or urosepsis?
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
How is catheter-associated UTI treated?
Remove catheter (but give stat doses before removal of infected catheter) Gentamicin or Amikacin (stat 30-60 mins before the procedure)
What eye condition can be caused by candida?
Endophthalmitis
How is cryptococcus diagnosed?
EIA looking for antigen components
Which organisms cause tinea capitis and onychomycosis?
Tinea capitis: Tricophyton rubrum, Trichophyton tonsurans
Onychomycosis: Tricophyton spp., Epidermophyton spp. and Microsporum spp.
List the classes of beta-lactam containing antimicrobials.
Penicillins
Cephalosporins
Carbapenems
Monobactams
Outline the different generations of cephalosporins.
1st: Cephalexin
2nd: Cefuroxime
3rd: Ceftriaxone, Cefotaxime, Ceftazidime
Which classes of antibiotic have bacteriostatic action?
Tetracyclines
Macrolides
Chloramphenicol
Which classes of antibiotic have bactericidal action?
Beta lactams Glycopeptides Aminoglycosides Quinolones Rifampicin Nitroimidazoles
For each of the three types of antibiotic pharmacokinetics, list the classes of antibiotics that fall into that category.
Type 1 (concentration-dependent): aminoglycosides, daptomycin, quinolones Type 2 (time-dependent): all beta-lactams, erythromycin, linezolid Type 3 (mixed): tetracyclines, oxazolidinones, vancomycin, clindamycin, azithromycin
How are mild and severe community-acquired pneumonias treated?
Mild: amoxicillin
Severe: co-amoxiclav + clarithromycin
How are hospital-acquired UTIs treated?
Cephalexin or co-amoxiclav
How is aspiration pneumonia treated?
Cefuroxime + metronidazole
Name an antibiotic that has good cover against pseudomonas but poor anaerobe cover.
Ciprofloxacin
Name two Gram-negative lactose-fermenting rods.
E. coli
Klebsiella
NOTE: lactose fermentation status is based on growth on MacConkey agar
Which drug is red man syndrome associated with?
Vancomycin
Characterised by pain and thrombophlebitis
Describe the mechanism of HIV entry into CD4 cells.
- Initial interaction between gp120 and CD4.
- Conformational change in gp120 allows for secondary interaction with CCR5.
- The distal tips of gp41 are inserted into the cellular membrane.
- gp41 undergoes significant conformational change; folding in half and forming coiled-coils. This process pulls the viral and cellular membranes together, fusing them.
Describe the appearance of erysipelas and state which organism is most commonly implicated.
Red, well demarcated, oedematous rash on the face
Usually caused by S. pyogenes
What is the most common cause of acute viral haemorrhagic cystitis in children?
Adenovirus
Which organism causes gas gangrene? Describe its presentation.
Clostridium perfringens
Oedema and discoloration with necrotic bullae
Soil-transmitted through breaks in the skin
For which conditions is post-exposure prophylaxis available?
Rabies
HIV
Tetanus
List some examples of anaerobic bacteria.
Actinomyces Bacteroides Clostridium Porphyromonas Propionibacterium
Which types of bacteria are chocolate agar used to grow?
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
What is sporotrichosis?
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
What are the HACEK organisms?
Fastidious Gram-negative bacteria that are an unusual cause of infective endocarditis Haemophilus Aggregatibacter Cardiobacterium Eikenella Kingella
What is the mechanism of action of tenofovir?
NucleoTide reverse transcriptase inhibitor (NtRTI)
What is the mechanism of action of lamivudine and entecavir?
Nucleoside reverse transcriptase inhibitor (NRTI)
List some examples of obligate intracellular bacteria and protozoa.
Bacteria: Chlamydia, Rickettsia, Coxiella, Mycobacteria
Protozoa: toxoplasma, cryptosporidium, leishmania
Which organisms can be identified with wet slide microscopy?
BV
TV
Candida
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
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
