Path - Microbiology Flashcards
Match each numbered class of antibiotic with its lettered mechanism of action/ description
- Beta lactams
- Oxazolidinones
- Glycopeptides
- Aminoglycosides & tetracyclines
- Macrolides & chloramphenicol
- Fluoroquinolones
- Nitroimidazoles
- Rifamycins
- Sulphonamides and diaminopyrimidines
A. Inhibits a subunit of DNA gyrase to disrupt DNA replication
B. Binds to pentapeptides to prevent them from being used to form peptidoglycan
C. Binds to the 50s subunit of bacterial ribosomes
D. Interferes with folic acid metabolism, indirectly affecting DNA replication
E. Binds to the 30s subunit of bacterial ribosomes
F. Inactivates transpeptidases which are important for incorporating peptidoglycan into the bacterial cell wall
G. Binds to the 23s component of the 50s subunit of bacterial ribosomes to prevent formation of the initiation complex
H. Produces an active intermediate under anaerobic conditions which causes DNA strand breakage
I. Inhibits protein synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation
- Beta lactams - F. Inactivates transpeptidases which are important for incorporating peptidoglycan into the bacterial cell wall
- Oxazolidinones - G. Binds to the 23s component of the 50s subunit of bacterial ribosomes to prevent formation of the initiation complex
- Glycopeptides - B. Binds to pentapeptides to prevent them from being used to form peptidoglycan
- Aminoglycosides/ tetracyclines - E. Binds to the 30s subunit of bacterial ribosomes
- Macrolides/ chloramphenicol - C. Binds to the 50s subunit of bacterial ribosomes
- Fluoroquinolones - A. Inhibits a subunit of DNA gyrase to disrupt DNA replication
- Nirtoimidazoles - H. Produces an active intermediate under anaerobic conditions which causes DNA strand breakage
- Rifamycins - I. Inhibits protein synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation
- Sulphonamides and diaminopyrimidines - D. Interferes with folic acid metabolism, indirectly affecting DNA replication
A patient being treated for a separate infection develops diarrhoea, fever, and nausea. They are diagnosed with moderate pseudomembranous colitis.
Which would be the most appropriate antibiotic to give?
A. Ceftriaxone B. Metronidazole C. Gentamicin D. Vancomycin E. Cefotaxime
B. Metronidazole
Metronidazole is used to treat mild-moderate C. difficile colitis, with vancomycin and fidaxomicin being reserved for severe disease. This is partially to avoid resistance to vancomycin developing, and partially because it is nephrotoxic and requires careful monitoring of the patient’s renal function. Cephalosporins should not be used in this case as they are associated with causing C. difficile colitis. Most antibiotics have some association with C. diff diarrhoea, especially: clindamycin, cephalosporins, fluoroquinolones, and broad spectrum penicillins (the broader the spectrum, the more likely diarrhoea is).
A known cystic fibrosis patient presents to hospital with purulent cough, fever, and fatigue. Pseudomonas infection is diagnosed.
What would be the most appropriate antibiotic to give?
A. Tetracycline B. Cefotaxime C. Ketoconazole D. Vancomycin E. Gentamicin
E. Gentamicin
Though they are ototoxic and nephrotoxic, and so levels must be monitored, gentamicin and tobramycin (both aminoglycosides) are particularly effective against P. aeruginosa infection.
Pseudomonas can be treated with aminoglycosides (e.g. amikcacin, gentamicin, tobramycin) or with broad-action beta lactams (tazocin, meropenem, ceftazidime) or fluoroquinolones (ciprofloxacin).
Match the numbered example to the lettered mechanism of resistance (lettered options may be used more than once)
- ESBL E. coli resistance to ceftriaxone
- Resistance to macrolides
- Resistance to trimethoprim and sulphonamides
- MRSA resistance to flucloxacillin
- Resistance to Rifampicin
A. Impaired uptake of the antibiotic B. Alteration of the target C. Enzymatic inactivation of the antibiotic D. Enhanced antibiotic efflux E. Bypass of antibiotic-sensitive step
- ESBL E. coli resistance to ceftriaxone - C. Enzymatic inactivation of the antibiotic
- Resistance to macrolides - B. Alteration of the target
- Resistance to trimethoprim and sulphonamides - E. Bypass of antibiotic-sensitive step
- MRSA resistance to flucloxacillin - B. Alteration of the target
- Resistance to Rifampicin - B. Alteration of the target
ESBL stands for extended-spectrum beta lactamase, and organisms which produce it can inactivate a wide range of antibiotics including third generation cephalosporins.
Flucloxacillin-resistant strains (e.g. MRSA) have altered transpeptidase enzymes (penicillin-binding proteins) which prevent beta-lactams from binding. However Flucloxacillin is stable against beta lactamases.
NB: If in doubt, say altered target
A woman is brought to hospital with suspected meningitis. Blood is taken and an LP is performed before commencement of empirical antibiotics. Upon analysis the CSF shows clear fluid with raised lymphocyte and protein counts, but normal glucose.
What is the most likely causative organism?
A. Haemophilus influenzae B. Streptococcus pneumoniae C. Mycoplasma tuberculosis D. Enterovirus E. Herpes simplex
D. Enterovirus
This is a case of aseptic meningitis: viral meningitis. It is so named because the causative organism does not cause sepsis, and is the most common form of CNS infection. This CSF result usually indicates viral meningitis, for which non-polio enteroviruses (i.e. echoviruses and coxsackie viruses) are responsible for 80-90% of cases. This condition most frequently occurs in children under 1 year old, and presents with photophobia, neck stiffness, and photophobia, and a non-specific rash may also be seen. However the course of the disease is self-limiting and resolves in 1-2 weeks.
It is worth looking up and memorising the CSF findings in each different type of meningitis.
A 65 year-old man, who is a big fan of unpasteurised cheese, presents with headache and neck stiffness. Blood cultures produce a Gram-positive rod.
What is the most likely causative organism?
A. Listeria monocytogenes B. Cryptococcus neoformans C. Haemophilus influenzae D. Streptococcus pneumoniae E. Neisseria meningitidis F. Escherichia coli G. Mycobacterium tuberculosis
A. Listeria monocytogenes
Listeria monocytogenes is one of the three most common causes of meningitis in immunocompromised (including elderly and very young) patients along with group B Streptococcus and Escherichia coli. The relatively advanced age (>50) of the patient, his penchant for unpasteurised cheese, and the presence of a Gram-positive rod imply the cause is Listeria monocytogenes.
A 33 year-old man presents with headache and neck stiffness. Treating a CSF sample with the Indian ink stain reveals the causative organism.
What is the most likely causative organism?
A. Listeria monocytogenes B. Cryptococcus neoformans C. Haemophilus influenzae D. Streptococcus pneumoniae E. Neisseria meningitidis F. Escherichia coli G. Mycobacterium tuberculosis
B. Cryptococcus neoformans
The India ink stain is useful for staining the polysaccharide capsule surrounding Cryptococcus neoformans (which is a yeast). Cryptococcus is a less common cause of meningitis and should not occur unless the patient is in some way immunocompromised. Accordingly, this patient should be offered an HIV test.
Which option describes the best treatment for meningitis to be given as soon as blood cultures and CSF have been taken if the causative organism is unknown?
A. Meropenem 6g/d or Ceftazidime 6g/d
B. Aciclovir 10mg/kg I.V. tds, Ceftriaxone 2g I.V. bd with Amoxicillin 2g I.V. 4-hourly if >50 or immunocompromised
C. Ceftriaxone 4g/d or Chloramphenicol 75-100mg/kg/d
D. Ampicillin 12g/d plus Gentamicin or Benzylpenicillin 18-24 mg/d
E. Ceftriaxone 2g I.V. bd with Amoxicillin 2g I.V. 4-hourly if >50 or immunocompromised
E. Ceftriaxone 2g I.V. bd with Amoxicillin 2g I.V. 4-hourly if >50 or immunocompromised
The management protocol for meningitis is to immediately take blood cultures and perform an LP. An LP must not be performed if there are signs of raised intra-cranial pressure (decreased GCS, papilloedema on fundoscopy, seizures, or focal neruological deficits). As soon as this has been done, empirical treatment with Ceftriaxone 2g I.V.bd with Amoxicillin 2g I.V. 4-hourly if >50 or immunocompromised is begun. Once culture results are available and the organism is known, more targeted antibiotic regimes can be started. Aciclovir is added to this starter regime if there is suspicion of viral meningio-encephalitis.
NB: Amoxicillin is added in very young or elderly or immunocompromised patients as they are vulnerable to listeria monocytogenes, which will not be killed by Ceftriaxone.
NB: Ceftriaxone is not used in neonates because it displaces bilirubin from albumin which may cause biliary sludging - cefotaxime is used instead
A 19 year-old man returns from holiday in Spain. Four weeks later, he develops a hot, swollen, painful, red knee joint, with an effusion. The knee is tapped, and 20ml of cloudy yellow fluid is withdrawn. Microbiology reveals Gram-negative intracellular diplococci.
What is the most likely causative organism?
A. Neisseria meningitidis B. Haemophilus influenzae C. Streptococcus viridans D. Escherichia coli E. Streptococcus pneumoniae F. Neisseira gonorrhoeae G. Staphylococcus Aureus
F. Neisseria gonorrhoeae
STIs can lead to septic arthritis if untreated, and this should be suspected particularly in young patients or patients with a suspicious sexual/ travel history.
A previously well 19 year-old student arrives in casualty septic, pyrexial, and confused, with a temperature of 39 degrees. He has a stiff neck, and an LP is performed
Which of the following is the LP most likely to show?
A. Gram positive bacilli B. Gram negative bacilli C. Gram positive coccobacilli D. Gram negative cocci in large clusters E. Gram positive cocci in chains
E. Gram positive cocci in chains
Gram positive cocci in chains implies the pathogen is Streptococcus pneumoniae - one of the three most commonly responsible pathogens in meningitis of immunocompetent patients along with Neisseria meningitidis and Haemophilus influenzae. The three most common organisms causing meningitis in immunocompromised patients are group B Strep (Streptococcus agalactiae), Listeria monocytogenes, and Escherichia coli.
‘A’ describes Listeria and ‘B’ describes E. coli. ‘C’ incorrectly describes H. influenzae, as it is actually a Gram negative coccobacillus. ‘D’ incorrectly describes N. meningitidis, which is a Gram negative diplococcus.
A 6 year-old boy arrives in casualty septic, pyrexial, and confused with a temperature of 39 degrees. He has a stiff neck, and a lumber puncture reveals Gram-negative coccobacilli.
What is the most likely causative organism?
A. Neisserisa meningitidis B. Haemophilus influenzae C. Streptococcus viridans D. Escherichia coli E. Streptococcus pneumoniae F. Neisseira gonorrhoeae G. Staphylococcus Aureus
B. Haemophilus influenzae
Haemophilus influenzae is a coccobacillus, and so is halfway between a rod and a coccus. Haemophilus influenzae is one of the three main causes of meningitis in immunocompetent individuals (the other two being Streptococcus pneumoniae and Neisseria meningitidis). The main three causes of meningitis which only occur in immunocompromised patients are E. coli, Group B Streptococci (S. agalactiae), and Listeria. These organisms most commonly cause meningitis in neonates.
A 22 year-old has a mild fever for several months, and no cause can be found. After 2 months, blood cultures come back positive for Gram-positive cocci.
What is the most likely causative organism?
A. Neisserisa meningitidis B. Haemophilus influenzae C. Streptococcus viridans D. Escherichia coli E. Streptococcus pneumoniae F. Neisseira gonorrhoeae G. Staphylococcus Aureus
C. Streptococcus viridans
Streptococcus viridans is a slow-growing organism which can cause low-level systemic infection. It normally resides in the mouth, hence dental surgery may allow it to enter the bloodstream. Streptococcus viridans causes subacute bacterial endocarditis as bacteria in the bloodstream adhere to heart valves (usually the mitral, but the tricuspid in IVDU).
Subacute bacterial endocarditis requires prior damage of the heart valves in order to take hold. The extracellular matrix of the valves is accordingly damaged by the body’s inflammatory response (hence subacute bacterial endocarditis is classified as a type III hypersensitivity reaction). Subacute bacterial endocarditis usually affects the mitral valve because it is constantly subjected to the high pressures of the left heart, and so is slightly damaged even in healthy people, which makes it easier for bacteria to infect.
NB: This is not to be confused with rheumatic fever: a type II hypersensitivity reaction occurring after Streptococcus pyogenes infection.
A 35 year-old patient presents with clustered red pustules on his skin, fever, abdominal pain, and blood in the stool. A routine HIV test is positive. During the history the patient reveals they bought a kitten several months ago.
What is the most likely diagnosis?
A. Toxoplasmosis B. Viral haemorrhagic fever C. Q fever D. Bacilliary angiomatosis E. Brucellosis
D. Bacilliary angiomatosis
This infection has been caused by Bartonella henselae, which is a slightly curved Gram-negative rod. Bartonella is found on cat’s paws, particularly in kittens (which also scratch more than adult cats as they cannot retract their claws). Bartonella usually only causes Cat-scratch disease, which features a macule (later pustule as the centre ulcerates) at the site of inoculation, along with regional adenopathy and systemic flu-like symptoms. In some, rarer cases, Cat-scratch disease can cause more severe manifestations e.g. pneumonia, arthritis, hepatitis.
In immunocomprimised patients, Bartonella can cause bacilliary angiomatosis - the formation of vascular lesions within multiple organ systems leading to bleeding. The skin is most often involved, but almost any organ system can be affected (hence the GI bleeding in this patient.
Why should vancomycin not be given orally apart from in case of pseudomembranous colitis?
A. It is enterotoxic
B. It is not absorbed from the gut
C. It undergoes extensive first-pass metabolism
D. It has been known to rarely cause osteonecrosis of the jaw
E. The oral form is too expensive
B. It is not absorbed from the gut
Vancomycin is always given I.V. because it cannot be absorbed form inside the gut. The exception to this is when treating pseudomembranous colitis, as in that case it is ideal to not absorb the vancomycin.
A 30 year-old man presents with jaundice and haemoptysis. He has felt ‘run-down’ since returning from a canoeing trip to the USA a little over a month ago. On questioning he admits to having muscle aches (especially in his calves), and headaches. On examination there is hepatomegaly and conjunctival suffusion. He reveals that his trip was to a remote region with a lot of rodents, and that there was heavy rainfall during his stay.
What is the most likely causative organism?
A. Rabies lyssavirus B. Bacillus anthrax C. Brucella melitensis D. Bartonella henselae E. Leptospira interrogans F. Coxiella burnetii G. Borrelia burgdorferi
E. Leptospira interrogans
Leptospirosis (also known as Weil’s disease) usually presents with sudden onset headache, fever, chills, abdominal pain, muscle pain in the lower limbs (particularly the calf muscle), and conjunctival suffusion (resembles conjunctivitis, but without inflammatory exudates - virtually pathognomic of leptospirosis). The gold standard for diagnosing L. interrogans infection is microscopic agglutination testing.
Jaundice, severe haemoptysis, cardiac arrhythmia, acute renal failure, a maculopapular rash, and rarely mental state changes may all occur in advanced disease. Leptopspirosis consists of two phases: the initial acute/ septic phase features the flu-like symptoms, and the immune phase afterwards which features the more severe and rarer symptoms.
Risk factors include travel to tropical/ endemic regions, travel/ residence in flooding regions especially after heavy rainfall, water sports, and exposure to infected animal urine (particularly rats). Leptospirosis is diagnosed using the Faine’s criteria adopted by the WHO which accounts for clinical, epidemiological, and laboratory findings. Leptospira interrogans can inhabit freshwater for long period of time.
A 25 year-old man presents to his GP with lethargy for a month accompanied by headaches and fever. On examination, he had a temperature of 39 degrees and splenomegaly. He has recently travelled to Italy. Small Gram-negative coccobacilli were seen on culture with Castaneda’s medium.
What is the most likely causative organism?
A. Rabies lyssavirus B. Bacillus anthrax C. Brucella melitensis D. Bartonella henselae E. Leptospira interrogans F. Coxiella burnetii G. Borrelia burgdorferi
C. Brucella melitensis
Brucella is a Gram negative intracellular coccobacillus which causes a zoonotic infection. Brucellosis typically causes undulating fevers, headache, arthralgia, night sweats, and anorexia in its initial stages. Later the infection may become more serious and lead to neural infection, endocarditis, liver abscesses, spondylitis, and epididymo-orchitis.
A 22 year-old student presents to her GP upon return from a biology field trip with a lesion on her leg which is 5cm in diameter and flat, with a red edge and a dim centre. She also mentions feeling tired and suffering form headaches. On examination, the GP noted a fever of 38 degrees and an irregular heart rate.
What is the most likely causative organism?
A. Rabies lyssavirus B. Bacillus anthrax C. Brucella melitensis D. Bartonella henselae E. Leptospira interrogans F. Coxiella burnetii G. Borrelia burgdorferi
G. Borrelia burgdorferi
This is a history of Lyme disease. The best known feature of Lyme disease is an expanding rash known as erythema migrans (seen in ~80% of patients); it has a target/ bullseye appearance and is caused by infection of the skin by Borrelia. The rash appears within the first couple of weeks after a tick-bite, and is accompanied by generic flu-like symptoms.
Once disseminated, Borrelia can cause neurological compliations (facial palsy, radiculopathy, meningitis, encephalitis, peripheral neuropathy), cardiological complications (myocarditis leading to abnormal rhythms - palpitations), and arthritis.
A tanner on holiday from India presents to hospital with an ulcerating papule on his hand. On inspection of the ulcer, the centre was black and necrotic. Gram-positive rods grew on blood agar culture and responded to treatment with large doses of penicillin.
What is the most likely causative organism?
A. Rabies lyssavirus B. Bacillus anthrax C. Brucella melitensis D. Bartonella henselae E. Leptospira interrogans F. Coxiella burnetii G. Borrelia burgdorferi
B. Bacillus anthrax
A tanner works with animal hides, which provide a perfect environment for Bacillus anthrax to proliferate, and so the occupation in this case gives a strong clue.
A 49 year-old man was admitted from A&E with a 3-day history of worsening right arm pain and a 1-day history of hypersalivation, agitation, and generalised muscle twitching. Vital signs and blood tests were normal but he later became confused. He developed renal failure and died four days later.
What is the most likely causative organism?
A. Rabies lyssavirus B. Bacillus anthrax C. Brucella melitensis D. Bartonella henselae E. Leptospira interrogans F. Coxiella burnetii G. Borrelia burgdorferi
A. Rabies lyssavirus
Rabies lyssavirus is transmitted through saliva, and once a person is infected the virus enters their peripheral nervous system and spreads to their CNS. There is an incubation period of 1-3 months, but once the virus spreads to the CNS and the patient become symptomatic, the patient almost invariably dies - only a handful of people have ever survived symptomatic rabies.
Vaccination provides some protection, and prognosis is good if treatment is started before symptoms begin. If unvaccinated, the patient will need three doses of vaccine along with human rabies immunoglobulin, which is 100% effective if given within 14 days If already vaccinated, a person need only receive post-exposure vaccination to be treated.
Symptoms begin with generic flu-like symptoms, then progress to behavioural changes with aggression, paranoia, terror, paralysis, delerium, and eventually coma and death. A treatment known as the Milwaukee protocol was tried which involved placing patients in a chemically induced coma and giving anti-viral treatment, but was not successful and is no longer tried.
Don’t get rabies kids
A French farmer visiting family in the UK presents with fever and fatigue of two weeks duration. He also admits a dry cough and some abdominal pain. Examination reveals reduced chest expansion and crackles on auscultation, as well as tenderness over the right hypochondriac region and hepatomegaly. The farmer keeps a range of livestock for breeding and has close contact with the animals including assisting in their giving birth.
What is the most likely causative organism?
A. Coxiella burnetii B. Borrelia burgdorferi C. Leptospira interrogans D. Staphylococcus aureus E. Streptococcus viridans
A. Coxiella burnetii
Coxiella burnetti causes Q fever. Q fever is difficult to distinguish from other infections, particularly brucellosis as it shares the same reservoirs (goats, cattle) and has a similar presentation (pneumonia, flu-like illness, hepatitis). Q fever may also result in focal infections in a wide variety of systems. Around 5% of Q fever cases will proceed to a chronic infection, which confers an increased chance of developing endocarditis. Q fever is a significant problem in pregannt women, and has a distinct presentation.
Why is penicillin less effective on infections with a high bacterial load?
A. The bacteria form dense populations which physically prevents drugs from reaching the centre
B. Horizontal gene transmission of resistance genes is more likely in these populations
C. There is a greater concentration of beta-lactamase produced
D. Greater populations are more likely to include other bacterial species which are not susceptible to penicillin
E. Penicillin is only active whilst bacteria are replicating which occurs less when their numbers are greater
E. Penicillin is only active whilst bacteria are replicating which occurs less when their numbers are greater
As bacterial numbers increase, their rate of growth slows, as resources become more scarce. Penicillin only affects bacteria in the growth phase, and so if the bacteria are not growing at a significant rate, penicillin will have no effect.
Which of the following options most accurately describes a prion disease?
A. A disease with a genetic form inherited in an autosomal recessive fashion
B. A sub-variant of amyloidosis
C. Disease caused by alpha-helical configured proteins
D. A pure protein infectious agent which causes untreatable neurodegeneration
E. A progressive neurodegenerative condition similar to dementia, causing steady decline over many years
D. A pure protein infectious agent which causes untreatable neurodegeneration
Prion diseases are caused by the presence of misfolded proteins (prions) in the CNS which cause rapid and untreatable neurodegeneration.
The aetiology of prion disease is not thoroughly understood, as it is incredibly rare (~1 in a million). What is known is that the prion protein (PrP) exists in normal organisms and is not harmful, though its normal function is unknown. PrP can become misfolded to produce a prion. A prion is distinguished by its beta-sheet configuration (PrP normally has an alpha-helical configuration) which makes it incredibly resistant to proteases, which means it accumulates in the CNS, then aggregates to form PrP amyloid plaques which cause neurodegeneration (however prion disease is separate from amyloidosis). Prions are somehow able to misfold other PrP to also become prions, and so behave like infectious agents.
The resilience of prions means that they cannot reliably be removed from surgical instruments, even with extreme heat or radiation. Any instruments used in surgery on a prion-infected patient must be destroyed.
Whilst prion disease is steadily progressive, once symptoms begin it progresses rapidly, causing death in 3 months - 2 years depending on the type. However incubation periods may be extremely extensive, with periods of 45 years being reported amongst Kuru patients in Papua New Guinea.
What is the most common form of prion disease?
A. Kuru B. Iatrogenic Creutzfeld-Jacob disease C. Gerstmann-Straussler-Sheinker syndrome D. Variant Creutzfeld-Jacob disease E. Sporadic Creutzfeld-Jacob disease
E. Sporadic Creutzfeld-Jacob disease
Sporadic CJD represents ~80% of all prion disease, and affects older people (mean age of onset is 65). SCJD causes rapid dementia with myoclonus, cortical blindness, lower motor neuron signs, and akinetic mutism (dysarthria with akinesia/ ataxia). The cause of sCJD is unknown.
Signs of sCJD include: incresed signal in the basal ganglia on MRI, periodic triphasic complexes on EEG, presence of S100 and 14-3-3 neurodegenerative markers, and spongiform vacuolation and PrP amyloid plaques on biopsy.
Which statement is false of sporadic Creutzfeld-Jacob disease?
A. Median survival time after diagnosis is <6 months
B. Tonsillar biopsy can be diagnostic
C. EEG usually shows periodic complexes
D. Mean age of onset is 65
E. CSF markers (S100, 14-3-3) of neuronal damage may be elevated
B. Tonsillar biopsy is diagnostic
Tonsillar biopsy is of no use in sCJD, but is 100% sensitive and specific in variant CJD.
Which statement is true of variant Creutzfeld-jacob disease?
A. The disease mainly affects elderly people
B. vCJD is more rapidly progressive than sporadic CJD
C. The initial symptoms are always neurological
D. An MRI typically shows the pulvinar sign
E. EEG is usually abnormal
D. An MRI typically shows the pulvinar sign
Variant CJD occurs in younger people (median onset is 26) and is slower progressing than sCJD. It usually presents with psychiatric symptoms (anxiety, paranoia, hallucinations, dysphoria) and neurological symptoms appear later (peripheral neuropathy, ataxia, myoclonus, chorea, dementia).
Signs of vCJD include: a positive tonsillar biopsy (100% sensitive and specific in vCJD), increased signal form the pulvinar nuclei in the posterior thalamus on MRI (pulvinar sign), and florid plaques seen on biopsy.
All bar one patients who have been known to contract vCJD have had the methyinine-methyinine polymorphism at codon 129 of the PRNP gene. It is not known why this association exists.
Which of the following statements is true?
A. The vast majority of cases of variant CJD have been found to be MM at codon 129 of the PRNP gene
B. Familial prion disease does not cause ataxia
C. In familial prion disease, mutations are usually inherited recessively
D. Familial CJD is more rapidly progressive than sporadic CJD
E. Variant CJD can be indicated by increased signal in the basal ganglia on MRI scans
A. The vast majority of cases of variant CJD have been found to be MM at codon 129 of the PRNP gene
All but one case
A 13 year-old patient presents with throat pain and fever. They deny cough, and examination shows tonsillar exudate. Their modified centor score is 5.
Which treatment should be given?
A. Benzylpenicillin B. Valaciclovir C. Co-amoxiclav D. Vancomycin E. Aciclovir
A. Benzylpenicillin
This is most probably a case of bacterial pharyngitis, as indicated by a high centor score, as a score of 3-4 indicates a 32-56% chance of a Streptococcal cause. As a result, benzylpenicillin should be given for 10 days.
A 78 year-old man is admitted to A&E with cough, dyspnoea, and confusion. His respiratory rate is 33 and his BP is 85/55. He is given an urgent chest X-ray and diagnosed with pneumonia.
How should this patient be managed?
A. Dishrge home with instructions to family to monitor him and return if symptoms don’t improve, give oral amoxicillin with erythromycin
B. Admit to a respiratory ward and give oral amoxicillin and clarithromycin
C. Consider ICU admission and give I.V. co-amoxiclav with clarithromycin
D. Admit to HDU and begin I.V. vancomycin
E. Admit to ICU, take blood cultures, then immdeiately start I.V. ceftriaxone with amoxicillin
C. Consider ICU admission and give I.V. co-amoxiclav with clarithromycin
A CURB-65 score would be used to calculate the predicted mortality, and by extension the severity of this patient’s disease.
Confusion - new onset, defined by an AMTS of 8 or less
Urea - Serum conc. > 7mmol/L
Respiratory rate - >30 breaths per minute
Blood pressure - less than 90 systolic or 60 diastolic
65 - aged 65 or over
This patient has a CURB-65 score of 4 and so should be given I.V. co-amoxiclav with clarithromycin and should be admitted to ITU. A score of 0 or 1 indicates possible home-based care, 2 indicates hospital-based care, and 3 or more indicates ITU admission. It is important to monitor for sepsis and remember the Sepsis 6:
Monitor urine output Take blood cultures Serial lactate measurements Give oxygen Give empirical antibiotics Give I.V. saline
A 65 year-old woman presents with jaundice and abdominal swelling. Examination reveals spider naevi and palmar erythema. She has a mild alcohol history, and denies I.V. drug use. She has three children, the first of which was a difficult birth with significant post-partum haemorrhage when she was 21. She mentions she has recently returned from holiday and that she had seafood from a questionable vendor.
What is the most likely cause of her symptoms?
A. Hepatitis A B. Hepatitis B C. Hepatitis C D. HIV E. Cytomegalovirus
C. Hepatitis C
This is a clinical picture of a woman with acute-on-chronic liver failure (also known as decompensated liver failure) as indicated by ascites (low albumin), spider naevi and palmar erythema (high oestrogens as the liver can no longer metabolise them). The seafood is a red herring (badoom cha) because though that could infect this patient with hepatitis A, it is a self-limiting illness that could not cause this extent of damage.
This woman most likely contracted hepatitis C from contaminated blood products given when she gave birth to her first child, as this was before the advent of hepatitis C screening in the UK (1991).
Why would amoxicillin be given in addition to ceftriaxone to treat meningitis?
A. Because ceftriaxone is not effective against Listeria
B. Because they have synergistic killing effects on bacteria
C. To give enhanced Gram negative cover
D. Because amoxicillin is effective against organisms which produce ESBLs
E. To cover atypical organisms
A. Because ceftriaxone is not effective against Listeria
Ceftriaxone is a third generation cephalosporins with good Gram positive and negative cover, but does not protect against Listeria, an important cause of meningitis in newborns and immunocompromised patients. Cheese may be contaminated with Listeria, and is an important clue in the history.
Which of the following is an antibiotic effective against a Beta-lactamase-producing organism?
A. Benzylpenicillin B. Piperacillin C. Tazobactam D. Amoxicillin E. Flucloxacillin
E. Flucloxacillin
Benzylpenicillin, piperacillin, and amoxicillin are all antibiotics of the penicillin class which are sensitive to beta-lactamase. Tazobactam is a beta-lactamase inhibitor which is given along with piperacillin, but which is not itself an antibiotic. Flucloxacillin is a member of the penicillin class, but is resistant to beta-lactamase.
A patient is brought to A&E with the signs of meningism, and an LP is immediately performed. The opening pressure is 35cm.
Which cause of meningitis is associated with an especially high opening pressure on LP?
A. Neisseria meningitidis B. Coxsackievirus C. Haemophilus influenza D. Cryptococcus neoformans E. Echovirus
D. Cryptococcus neoformans
Cryptococcus neoformans is a cause of meningitis usually seen only in HIV+ patients. It is well-known for causing a particularly high opening pressure on LP. Cryptococcus neoformans is a fungus that can be stained for using the India Ink stain.
Which of the following would not be a contraindication for LP in suspected meningitis?
A. Loss of sensation along the lateral side of the leg
B. Blurring of optic disc margins seen on fundoscopy
C. Unknown INR prior to procedure
D. Seizures
E. The presence of a spreading purpuric rash
C. Unknown INR prior to procedure
Unless there is a known clotting issue, this is not a contraindication. Some of the main contraindications to LP are: GCS reduction below 12 Continuous or uncontrolled seizures Focal neurology Papilloedema Infection at LP site Cardiac/ respiratory compromise Thrombocytopenia/ clotting abnormalities An extensive or spreading purpuric rash (i.e. one which indicates DIC which will derange clotting and make the procedure unsafe)
A 35 year-old woman presents to A&E with constant high fevers of three days duration. She also reports malaise, headache and constipation. She returned from India a week ago. Her temperature is 39, BP is 120/80, and heart rate is 80. Blood cultures reveal Gram negative rods.
What is the most likely diagnosis?
A. Malaria B. Dengue fever C. Typhoid D. Amoebic liver abscess E. SARS
C. Typhoid
When considering fever in the returning traveller, malaria and typhoid are the most common diagnoses and the most important to remember. Typhoid is caused by Salmonella typhi (though an essentially identical disease - paratyphoid - is caused by Salmonella paratyphi). Typhoid causes constant high fevers, headache, cough, malaise, and constipation (NOT DIARRHOEA), and features an insidious onset.
More distinctive features include rose spots (small red macules caused by bacterial emboli), relative bradycardia (Faget’s sign - the pairing of relative bradycardia with fever as usually a febrile patient would be tachycardic), intestinal haemorrhages resulting from colonisation of Peyer’s patches, and intestinal perforation.
S. typhi has flagella and so is motile. As a result, it can spread throughout the body and so typhoid can be picked up on blood cultures, where it will appear as a Gram negative rod. It can also lie dormant within the gallbladder, which is how the original ‘Typhoid Mary’ had recurrent disease.
A previously well 32 year-old man presents with breathlessness of 3 weeks’ duration, but no cough. A chest x-ray reveals no abnormality, but on exertional testing his oxygen saturations begin to decrease. Two different types of urinary antigen tests are performed and are negative. He is later diagnosed with pneumonia. Initial treatment is co-amoxiclav with clarithromycin, but he does not improve. A subsequent CT chest shows bilateral ground glass opacities.
What is the most likely cause of his illness?
A. Drug-resistant streptococcus pneumoniae B. Mycoplasma pneumoniae C. Pulmonary fibrosis D. Pneumocystis jiroveci E. Small cell lung cancer
D. Pneumocystis jiroveci
PCP used to stand for Pneumocystis carinii pneumonia, and is still used though the organism has been re-named Pneumocytsis jiroveci. PCP is an AIDS-defining illness and features a non-productive cough along with SOB, fever and generic pneumonia/ infection signs.
The presentation is generally insidious, and may feature a normal or non-specific CXR. A CXR may feature perihilar fine reticular shadowing, but a CT chest may be more helpful and may feature perihilar ground glass opacities particularly in the apical regions of the lungs. Decreased exercise tolerance or reduced oxygen saturations on exercise are classic of PCP. Standard treatment is with Co-trimoxazole (trimethoprim with sulphamexothazole).
The urinary antigen tests mentioned are for pneumococcal and legionella species. each test has very high specificity, but sensitivity of only around 60%, nevertheless negative tests suggest those options are less likely.
NB: PCP increases the risk of a pneumothorax
A patient presents with fever. They have recently returned from central Africa, where they grew up and to which they frequently travel. The patient recorded their fever at 40 degrees a few days ago, but the fever has now dissipated. The patient develops a widespread rash (parts blanching and parts non-blanching) and muscle ache, and the fever returns a couple of days later. A blood test reveals elevated CRP and a markedly decreased platelet count.
What is the most likely diagnosis?
A. Tuberculosis B. Malaria C. Typhoid D. Familial Mediterranean Fever E. Dengue fever
E. Dengue fever
Dengue fever is caused by a single-stranded RNA flaviviridae virus spread by the Aedes mosquito. Infection with the virus may cause either Dengue fever or Dengue haemorrhagic fever. It is a disease endemic to the tropics, and is classified as a neglected tropical disease, and is an important differential when considering fever in the returning traveller.
Primary infection usually causes Dengue fever (secondary infection may also cause it) which is characterised by fever, severe headache (especially retro-orbital), myalgia, arthralgia, anorexia, abdominal discomfort, and perhaps a maculopapular rash. The fever may be biphasic (saddleback fever) though this is relatively uncommon.
Dengue haemorrhagic fever may feature the symptoms above, but will include some of: petechiae/ echymoses, epistaxis, bleeding from the gums, internal bleeding leading to circulatory compromise.
Reduced platelet count is a defining feature of Dengue haemorrhagic fever, but may also be present in regular Dengue fever. Joint pain is common, and can be used to differentiate Dengue from Chikungunya, an arbovirius which may present similarly, but which features much worse debilitating joint pain.
There are four serotypes of Dengue fever, and infection with one generally confers immunity against that serotype but not the others. The big problem with Dengue fever, is that subsequent infection with another serotype results in a more severe infection. The pathogenesis of this is not fully understood, but it is known that antibodies against one serotype somehow enhance infection by another, and that the immune system plays a significant role in the pathogenesis of haemorrhagic fever. This is relatively rare (affecting only 2-4% of patients with secondary Dengue infection) but highly dangerous.
NB: Dengue fever often is asymptomatic or causes mild, vague symptoms (particularly in young children) in the same way that Polio is usually asymptomatic or mild, but can still be dangerous. The prevalence of Dengue infection means that it still exerts a significant disease burden worldwide.
NB: The rash in this question is a combination of non-blanching and blanching because the patient has developed a petechial rash in addition to the blanching maculopapular rash of Dengue fever.
A 27 year-old man presents to clinic with 1 week duration: fever, swollen lymph nodes in the neck, malaise, diarrhoea and a widespread maculopapular rash. A routine HIV test is positive, and on questioning the likely exposure to HIV occurred 4 weeks ago.
What is the most likely cause of his symptoms?
A. Influenza infection B. HIV seroconversion illness C. Toxoplasmosis infection D. Cryptosporidium infection E. Infectious mononucleosis
B. HIV seroconversion illness
Seroconversion refers to the time when the immune system begins to create antibodies to a pathogen. In patients with HIV this may be accompanied by a brief and self-resolving flu-like illness. This occurs roughly between 3-12 weeks after infection but varies from person to person.
Influenza and mononucleosis are good differentials for this illness, though the diarrhoea and time frame since exposure are more suggestive of seroconversion illness. Seroconversion illness only occurs in ~50% of patients.
Cryptosporidium and toxoplasmosis are parasitic diseases which should not cause significant disease in immunocompetent hosts. In immunocompromised patients cryptosporidium may cause severe diarrhoeal disease (and can cause mild symptoms in immunocompetent patients), and toxoplasma causes widespread infection but particularly affects the CNS causing abscesses and encephalitis (toxoplasmosis is one of the most common opportunistic infections in HIV/AIDS).
A 5 year-old boy is brought to the GP by his mother with coryzal symptoms, plus conjunctivitis, cough, and fever. The GP prescribes amoxicillin and sends the boy home. The mother brings the boy back two days later as he has developed a maculopapular rash which began at his hairline, and has now spread down his face onto his trunk. On inspection of the mouth, there are white spots on the buccal mucosa.
What is the most likely diagnosis?
A. Cytomegalovirus infection B. Influenza plus drug reaction C. Behcet's syndrome D. Henoch-Schonlein purpura E. Measles
E. Measles
Measles is an extremely infectious viral disease. It is covered by the MMR vaccine which confers a 93% or 97% rate of protection depending on whether one or two doses are given (according to CDC). The MMR vaccine is very effective, but confers a lower rate of protection against mumps (78-88%).
The classic presentation of mumps is a high fever with the three C’s: conjunctivitis, coryza (upper respiratory symptoms - rhinitis essentially), and cough. This initial phase lasts around three days and begins after a 10-14 day incubation period. During the initial phase, Koplik spots may appear - white spots on the buccal mucosa. After the initial phase the classic measles maculopapular rash appears, starting around the hairline and moving caudally.
A 46 year-old man presents to A&E with headache. On examination he is cachectic and there are several purple plaques on his skin, and white plaques on the side of his tongue. An HIV test is positive, his viral load is 200,000, and his CD4 count is 9. He is immediately started on HAART, but no action is taken over the headache. 2 weeks later he returns to A&E with a considerably worse headache accompanied by vomiting, neck stiffness, and reduced consciousness.
What is the most likely cause of the symptoms?
A. Subdural bleed B. Encephalitis C. TB D. Immune reconstitution E. Toxoplasmosis brain abscess
D. Immune reconstitution
Immune reconstitution inflammatory syndrome (IRIS) occurs when a patient with a low CD4 count has opportunistic infection, and is then started on anti-retroviral therapy. As the immune system reconstitutes it may cause either an unmasking or a paradoxical IRIS.
In unmasking IRIS, the immune system creates an inflammatory response against a previously unknown opportunistic infection, causing the normal symptoms of the disease. In paradoxical IRIS, there is an inflammatory response causing relapse of symptoms of a prior infection that has already been treated (blood cultures are often sterile).
The purple skin plaques mentioned are Kaposi’s sarcomas - a cancer caused by HHV8 which only appears in immunocompromised patients - and hairy leukoplakia (white plaque on the side of the tongue which cannot be wiped away) which also indicates an immunocompromised state.
Which is the following does not cause a ring-enhancing lesion on a CT scan of the head?
A. Encephalitis B. Toxoplasmosis abscess C. Tuberculoma D. Primary CNS lymphoma E. Tumour
A. Encephalitis
The acronym for causes of a ring-enhancing lesion on a head CT scan is MAGICAL DR:
M - metastasis
A - abscess (e.g. toxoplasmosis)
G - glioblastoma
I - infarct (subacute phase), inflammation (tuberculoma, neurocystericosis - tapeworm infection of CNS)
C - contusion
A - AIDS-related CNS disease
L - lymphoma (ring-enhancing appearance more common in immunocompromised)
D - Demyleinating disease (classically produces an incomplete ring)
R - radiation necrosis, resolving haematoma
At what CD4 count are HIV patients generally considered to be at high risk from opportunistic infections?
A. 50 B. 100 C. 200 D. 350 E. 500
C. 200
CD4 count is used to monitor the competence of HIV patients’ immune systems, and the lower it drops, the more opportunistic infections may take hold and they more severe these infections will be.
Viral load correlates inversely with CD4 count. HIV infection is comprised of three phases: eclipse, acute, and chronic. During the eclipse phase, the virus spreads and begins to infect cells, establishing a viral reservoir. In the acute phase, the immune system begins to produce antibodies to HIV which may cause a brief seroconversion illness (generic flu-like symptoms). Viral load rapidly peaks in the acute phase, and this is the first time HIV can be detected on a blood test. Viral load rapidly decreases to a point known as the ‘set-point’ which is important in prognosis, and from there chronic infection ensues with steady CD4 loss and progression to AIDS.
This is a link to an excellent Nature review article on HIV with some very good diagrams:
https://www.nature.com/articles/nrdp201535#Sec12
Via which cell surface molecules does HIV gain entrance to cells?
A. CXCR4 and CCR5 only B. CD8 C. HLA class I D. HLA class II E. CD4 and co-receptors
E. CD4 and co-receptors
The primary receptor for HIV is CD4, but co-receptors are also required for entry, most often the chemokine receptors CXCR4 and CCR5. Although HLA molecules are not important for the entry of HIV into host cells, they are important in mediating immunity, as certain HLA I (and to a lesser extent HLA II) subtypes are enriched in the naturally immune population (<1% infected people).
Which of the following is not a characteristic of beta lactams?
A. They generally won’t cross an intact BBB
B. They are secreted through bile
C. They have a relatively short-half-life
D. They are relatively non-toxic
E. They are cross-allergenic (e.g. penicillin allergy gives a 10% chance of allergy to carbapenems or cephalosporins)
B. They are secreted through bile
Beta lactams are renally excreted, and so an altered dose should be considered in patients with renal impairment.
Which of these antibiotics is most active against Gram negative organisms?
A. Chloramphenicol B. Clarithromycin C. Benzylpenicillin D. Vancomycin E. Linezolid
A. Chloramphenicol
Macrolides (clarithromycin), glycopeptides (vancomycin, teicoplanin), and oxazolidinones (Linezolid) are not generally active against Gram negative organisms. Whilst more advanced penicillins have increasing Gram negative coverage, benzylpenicillin is very narrow-spectrum and is not useful against Gram negative organisms.
Rank the following in terms of risk of opportunistic viral infections:
A. Solid organ transplant recipients B. Advanced HIV patients C. Patients on long-term steroids D. Allogenic stem cell transplant recipients E. Cytotoxic chemotherapy patients
1 - D. Allogenic stem cell transplant recipients 2 - B. Advanced HIV patients 3 - A. Solid organ transplant recipients 4 - E. Cytotoxic chemotherapy patients 5 - C. Patients on long-term steroids
Although all of these patients will be more vulnerable to opportunistic viral infections, those who have received allogenic bone marrow transplants are most heavily immunosuppressed (although long-term, these patients’ immunosuppression can be tapered off more than in solid organ recipients).
Which of the following presentations is unlikely to be caused by Varicella-Zoster virus infection of an immunocompromised patient?
A. Shortness of breath with cough and pleuritic chest pain
B. Inflammation of the eye, with rapidly progressing retinal necrosis visible on fundoscopy
C. A patient presenting with right-sided visuospatial neglect and right sided weakness worse in the arm than the leg
D. Widespread purple papular lesions on the skin of a man who has been steadily declining
E. A severely unwell 3 year-old child with a haemorrhagic, necrotic rash
D. Widespread purple papular lesions on the skin of a man who has been steadily declining
Varicella-Zoster virus (VZV) usually infect children, giving them the relatively harmless disease of chicken pox. VZV is a member of the herpes virus family (HHV3) and lies dormant in nerve ganglia after initial infection. It can reactivate later in life (particularly in the elderly) to cause shingles - a particularly painful vesicular rash that is confined to a dermatome.
In the immunocompromised VZV is a much more significant problem. Whilst it is generally true that - in a significantly immunocomproimised patient - any pathogen can infect any system, there are certain diseases that are particularly associated with VZV infection. These include pneumonitis (A), acute retinal necrosis (B), cerebral vasculopathy leading to stroke (C), purpura fulminans - acquired protein S deficiency resulting from VZV infection and leading to intravascular thrombosis and haemorrhage into the skin (E).
‘D’ describes Kaposi’s sarcoma - purple/brown papules or plaques that can only appear in the immunocompromised, and are classically associated with AIDS. Kaposi’s sarcoma is caused by HHV8, not VZV.
Match the lettered opportunistic infection with the numbered virus most likely to have caused it.
A. Post-transplant lymphoproliferative disease
B. Retinitis
C. Progressive multifocal leukoencephalopathy
D. Multi-dermatomal shingles
E. Haemorrhagic cystitis
- JC virus
- VZV
- EBV
- BK virus
- CMV
A. Post-transplant lymphoproliferative disease - 3. EBV
B. Retinitis - 5. CMV
C. Progressive multifocal leukoencephalopathy - 1. JC virus
D. Multi-dermatomal shingles - 2. VZV
E. Haemorrhagic cystitis - 4. BK virus
BK virus is a polyoma virus associated with haemorrhagic cystitis in bone marrow transplant patients, and nephropathy in renal transplant patients
Please examine the following hepatitis B serology results, which profile is consistent with past (cleared) hepatitis B infection?
A. HBV sAg (+), HBV core Ab (+), HBV sAb (-)
B. HBV sAg (-), HBV core Ab (-), HBV sAb (+)
C. HBV sAg (-), HBV core Ab (-), HBV sAb (-)
D. HBV sAg (-), HBV core Ab (+), HBV sAb (+)
D. HBV sAg (-), HBV core Ab (+), HBV sAb (+)
Since the past infection was cleared, there should be no surface antigen remaining. The significance of the presence of core antibodies is that the vaccine for hepatitis B only causes production of surface antibodies, therefore the presence of core antibodies helps differentiate cleared infection from vaccinated.
Which of the following would indicate endocarditis under the Duke classification clinical criteria?
A. Two separate positive S. viridans blood cultures
B. New tricuspid regurgitation with a fever of 38.5 and Janeway lesions and Osler’s nodes on the hands
C. Two separate positive S. aureus blood cultures with septic pulmonary infarcts and a history of I.V. drug use
D. Roth spots, Janeway lesions, Osler’s nodes, and a previous history of rheumatic heart disease
E. One positive H. influenzae culture in an IVDU with a fever of 39, conjunctival haemorrhage, and Roth spots
B. New tricuspid regurgitation with a fever of 38.5 and Janeway lesions and Osler nodes on the hands
Although realistically you would strongly suspect infective endocarditis in every one of these cases, the Duke criteria are very specific in terms of what does and does not confirm it.
The Duke criteria is as follows:
To definitely diagnose infective endocarditis you must have either:
Pathological evidence (histology showing vegetations)
Or Clinical evidence
Clinical evidence is divided into major and minor criteria. To confirm the diagnosis you need 2 major criteria, or 1 major and 3 minor criteria, or 5 minor criteria.
Major criteria:
1) Evidence of microorganisms in the blood
NB: if S. viridans, S. bovis, HACEK group, S. aureus, enterococci, then only two separate cultures are needed. If other organisms are detected, then either two samples >12 hours apart are needed, or all 3 or the majority of 4 samples have to be positive
2) Evidence of endocardial involvement (signs on echocardiogram or new valvular regurgitation)
Minor criteria:
1) Predisposing heart condition or IVDU
2) Fever ≥ 38
3) Vascular events e.g. septic pulmonary emboli, Janeway lesions, intracranial haemorrhage
4) Immune events e.g. Roth spots, Osler’s nodes, glomerulonephritis
5) Cultures or biochemical evidence of infection that does not meet the major criteria
6) Echo findings indicating infective endocarditis but not sufficient to meet the major criteria
Luke Moore says to learn this in his PUO lecture
Which of the following most decreases the likelihood of a patient having giant cell arteritis?
A. An ESR of 40 (not hugely raised) B. No scalp tenderness on palpation C. Age of 37 D. No visual impairment E. Ferritin of <500
C. Age of 37
It is a good rule of thumb that people do not get giant cell arteritis below the age of 50
Which of the following investigations should be part of a patient’s initial work-up for a pyrexia of unknown origin?
A. Cryoglobulins B. HIV test C. CT CAP D. Anti-dsDNA antibody screen E. Brucella serology
B. HIV test
All patients would ideally get an HIV test on admission to hospital, especially for PUO.
