1
Q
If a disease is rare, more likely a false positive or negative?
A
The risk of false negative and false positive changes with how frequently a disease is seen in the community (and with the quality of a test). In simple terms, if a disease is very rare, a false positive is more likely and should be corroborated with other information
2
Q
What is sensitivity?
A
The proportion of people with the disease who have a positive test
A/(A + B)
3
Q
What is specificity?
A
The proportion of people without the disease who have a negative test
D/(C + D)
4
Q
What are M, C and S?
A
Microscopy culture and sensitivity
5
Q
What is microscopy?
A
- Cell count
- Gram stain
- Direct visualisation of organisms
6
Q
What is culture?
A
- Difficult culture media
- Slopes
7
Q
What is sensitivity in terms of M, C and S?
A
- EUCAST disc testing- use this test organism with antibiotics and see if antibiotic will work
- Strips
8
Q
Many samples – pus, blood, sputum, urine – are sent for MCS, but what does that mean?
A
- M - If from a sterile site – joint/CSF – the Gram stain is performed, this is not done for all samples
- C – different culture media are set up based on the likely bacteria causing infection at the site, some are generic, some look for specific groups of organisms e.g. anaerobes, others specific organism – e.g. gonorrhoea in a GU swab- look at what has grown
- S – If a relevant pathogen grows, we will set up sensitivity tests on a plate. This will show which antibiotics are likely to be effective in practice.
9
Q
What are blood tests for detection for immunity?
A
- IgG – previous infection
- IgM – current infection (or reactivation)
- Complement fixation tests (being phased out)
10
Q
What are blood tests for detection of a pathogen?
A
- Blood culture - M,C & S
- Polymerase chain reaction (PCR)- HIV, Hep C, meningeal coccus or pneumoniae coccus
- Microscopy (malaria) /trypanosomiasis
11
Q
What are the generic tests?
A
- Blood cultures
- FBC (look for WBC= inflammation), U&E (to see if renal failure related to sepsis), LFT, CRP (inflammation, clotting, procalcitonin
12
Q
What are speficifc tests for infections?
A
- Pus from abscess – culture and sensitivity results
- Hepatitis B serology
- Meningococcal PCR on CSF
13
Q
What are CNS infections?
A
- Meningitis – fever, headache, neck stiffness. Sometimes meningococcal or viral rash
- Encephalitis – similar, fever, confusion and sometimes n/v (nausea/vomiting)
- Brain abscess – fever, headache, neurological impact depending on anatomical location, can lead to ventriculitis
14
Q
What is meningitis/ encephalitis?
A
Inflammation of the meninges/brain parenchyma
15
Q
How do we test for meningitis/ encephelitis?
A
- Radiology – CT head. MRI head (for encephalitis)
- Lumbar puncture – cerebrospinal fluid (CSF)- look at the colour of the flood and test it (turbid- bacteria, clear- normal CSF or viral infection). Look at WBC in CSF to see if viral or bacterial casue (bacterial more neutrophilic and viral more lymphocytic). Exceptions- late reaction is more lymphocytic. Protein and glucose also indicators.
*
16
Q
Treatment for meningitis/ encephalitis?
A
GIVE BROAD SPECTURM ANTIBIOTICS STRAIGHT AWAY DUE TO THE HIGH MORTALITY. THEN RESULTS OF CSF THEN THEN DECIDE WHAT TO GIVE
17
Q
What do CSF tests test for in meningitis/ encephalitis?
A
- Routinely tested for cell count, protein, glucose, MC&S
- Viral PCR (enterovirus, adeno, VZV, HSV, parechovirus)
18
Q
What are other tests other for CSF if CSF suggests meningitis/ encephalitis?
A
- Cryptococcal antigen
- Toxoplasma PCR
- TB culture
19
Q
What are non-CSF tests to test for meningitis/ encephalitis?
A
- Blood cultures (2 sets)
- Bacterial throat swab
- Blood for HIV and blood PCR (S. pneumoniae, N. meningitidis)
20
Q
What bacteria if adult has meningitis?
A
Adults if have meningitis- would have S. pneumoniae or N. meningitidis
21
Q
Elderly and neonates what bacteria if have meningits/ encephalitis?
A
Adults if have meningitis- would have S. pneumoniae or N. meningitidis, elderly have listeria, neonates would have Group B strep Agalactiae, E. coli and listeria.
22
Q
How do you test for meningitis and encephalitis?
A
- Not LP/CSF- as can cause coning (brain forced out of skull into SC) if high pressure in the brain
- For aspiration/excision- get samples
- Blood cultures
- Fungal/bacterial/parasitic/TB- looking to find if this is cause via blood tests
23
Q
n brain abscesses, there are a number of mechanisms of infection what are they?
A
- Severe ENT infection e.g. sinusitis can cause – often streptococcal/anaerobic.
- Infective endocarditis, infection of heart valves- endocarditis- bacterial from heart valves spread around the body, can spread to the brain.
- This can be staph or strep. Also post-operative, this can be a number of different pathogens. LP is not usually appropriate, can cause brain to herniate through the base of the skull.
- Sometimes abscesses are aspirated or excised, then send for MCS. Otherwise rely on blood cultures. In immunocomp – things like toxo are important.
24
Q
What are symptoms of upper RTIs?
A
Upper is common cold, sore throats, ear infections
25
What are symptoms of lower RTIs?
Lower RTI is bronchitis/ pneumonia
26
Difference between typical and atypical pneumonia?
‘Atypical’ pneumonia – caused by bacteria than the more common one
27
What is community acquired pneumonia caused by?
Community acquired pneumonia- caused by strep pneumoniae
28
How do you diagnose typical CAP?
Typical
Blood cultures (if severe)
Sputum for MC&S
29
How do you diagnose atypical CAP?
‘Atypical’ pneumonia screen if antibiotics failed, features not normal on X-ray, some causes may need other antibiotics
* Sputum for MC&S
* Viral PCR
* Mycoplasma (serology/PCR)
* Chlamydia (PCR)
* Legionella antigen in urine
30
Cause for atypical pneumonia? What drug is given?
Cause for atypical pneumonia is legionella pneumophilia- won’t respond to co-amoxiclav- suggest to add clartihromycin
31
Atypical pneumonia may be suspected if what?
* Failure of narrow spectrum antibiotics
* Unusual clinical features – rash/arthralgia
* Radiological features
* Epidemiology – travel
32
What is the viral name for pneumonia? How is it tested?
* Viral pneumonia/pneumonitis
* Respiratory viral PCR
33
How long does pulmonary TB take to develop?
Pulmonary TB- can take months/ years to develop
Disease requiring exposure then reactivation.
In addition, not all TB is active, we also detect and treat latent TB as this prevents reactivation in later life. In order to detect patients with TB – we can look at exposure or active infection.
34
What are the tests for pulmonary TB?
CXR
Exposure testing
* Mantoux- for if you have had close contact with somone like someone you are living with
* IGRA’s (interferon gamma release assay)- T-spot/Quantiferon
Active pulmonary infection
* 3 sputum samples
* 8+ weeks culture
* Whole-genome sequencing
* PCR
35
Respiratory tract infection in the immunocompromised host- fungal infection what are you likely to be susceptible to?
* Aspergillus fumigatus infection
* Cryptococcosis
* Mucormycosis
36
Respiratory tract infection in the immunocompromised host- bacterial infection what are you likely to be susceptible to?
* Nocardia sp.
* Gram-negatives – resistant
37
Respiratory tract infection in the immunocompromised host- what other infections are you susceptible to?
* CMV
* HHV6
* Pneumocystis jirovecii
* Non-tuberculous mycobacteria
* Measles
38
Respiratory tract infection in the immunocompromised host- what non-infective things are you susceptible to?
GvHD
Cryptogenic organising pneumonia
GvHD- graft vs. host disease
39
Respiratory tract infection in the immunocompromised host what tests are used?
* Bronchoscopy/biopsy samples
* Aspergillus/CMV blood tests
40
Skin and soft tissue infection- whata re the localised symptoms?
* Impetigo- crusting- spots on face, neck and back
* Erysipelas- deep skin infection
* Cellulitis- superficial skin infection
41
Skin and soft tissue infection- severe/ extensive symptoms?
Severe/extensive
Necrotising fasciitis- in deep planes of tissue and causes severe sepsis
42
What other infection can you have from skin and soft tissue infection?
Diabetic foot infection
43
How do you test for skin and soft tissue infection for localised?
* Wound swabs unhelpful from intact skin
* Blister fluid/pus is better
44
How do you test for skin and soft tissue infection for severe/ nectrotising fascitis?
* Blood cultures
* MRSA swabs
* Full history
45
For general skin and soft tissue infection what other tests do you need?
Look for MRSA swabs/status
Request full history - water contact/travel/animal contact
46
What are the tests for non-infected wounds for diabetic food infection?
* May be ‘weepy’ or ‘smelly’ but this is not evidence of infection
* Swabs may represent colonising flora only
47
What are the tests for diabetic foot infection for mild infection?
Mild infection
* Moderate/severe – debridement then
* deep sampling of bone/tissue
* Often in theatre
48
What are the symptoms of lower UTIs?
Lower UTI- cystits, dysuria, frequency and urgency
49
Symptoms of upper UTIs?
Upper UTI- renal angle pain, vomiting, fever
50
How do you test for a UTI?
Send CSU/MSU (catheter specimen of urine/ mid-sample urine) for MC&S
* Microscopy – WCC/RBC/epithelial cells
* Culture – Usually Gram-negatives, sensitivities given which are appropriate to clinical details
51
WHat is prostatitis? how do you diagnose?
Prostatitis- bacterial infection in the prostate
* Suspect in men with recurrent UTI
* Clinical examination is key
* Urine for MCS useful to target therapy
52
What is Epididymo-orchitis?
Epididymo-orchitis- inflammation of epididymis and/ or testicle- testicular pain and urinary tract symptoms
* 2 aetiologies – STI/enteric. Diagnosed on USS
* Need to investigate both after taking history
* Urine for MCS
* Urine/swab for chlamydia/Gonorrhoea NAAT (PCR)
53
What are intra-vascular infections and what are the tests?
* Endocarditis – native/prosthetic valve
* Pacemaker infection
* Vascular graft infection
Send multiple blood cultures
Three sets of Blood Cultures should be taken at different times during the first 24 hours in all patients with suspected endocarditis (can be same arm)
54
What are GIT infections?
Infectious diarrhoea
* Viral gastroenteritis
* Bacterial
* Parasitic infection
Clostridium difficile infection (CDI)
Liver abscess
Biliary tract infection
Diverticulitis
55
What are community acquired gastroenteritis categorised into?
bacterial and viral causes
Bacterial
* Salmonella sp.
* Shigella sp.
* E coli
* Campylobacter sp.
* C. difficile
Viral causes
* Rotavirus
* Norovirus
* Parasitic
* Cryptosporidium
* Giardia
56
Tests to request for infective gastroenteritis?
* Stool for M, C & S –bacterial testing, some labs will do more
* Stool for C. difficile testing – GDH, toxin PCR
* Stool for viral PCR – range of tests differs between labs
* Stool for ova, parasites and cysts (OCP)
57
For a liver abcess what tests are needed?
Imaging – USS/CT
History important
* Pyogenic (bacterial)
* Hydatid
* Amoebic
Pus (if safe to aspirate)
Blood cultures
Stool for OCP
Hydatid serology
58
What are biliary and diverticulus infections?
* Biliary - cholangitis, cholecystitis
* Diverticulitis – fistula, abscess, perforation
59
What tests are there for biliary infection?
* Bloods – FBC, U&E, LFT, Clotting, Amylase
* Blood cultures
* Imaging
* Bile/pus from surgery/aspiration
60
For blood borne virus testing e.g. HIV, Hep B and C what are the tests?
Look at both
Serology- Antibody (IgG, IgM) and Antigen (component of virus)
PCR- DNA/RNA from living or dead organisms (usually active infection)
61
For more specific HIV testing what is there?
* HIV Ab/Ag combined test
* HIV PCR
* HIV resistance testing
62
For Hep B testing:
What antigen is there after infection or vaccination?
What antigen is there when antibody develops?
What marker is their for chronic infection?
* HBsAg – after infection or vaccination
* HBcAg – acute infection, antibody then develops
* HBeAg – marker of infectivity/chronic infection
* HBsAg – Hepatitis B surface antigen
* HBcAg – Hepatitis B core antigen
* HBeAg – Hepatitis Be antigen
* Anti-HBc, Anti-HBe, Anti-HBs - antibodies
63
What is the test for Hep C?
* Hepatitis C antibody
* Hepatitis C PCR
64
What is syphilis testing?
Detection by PCR
Serology
Screening with IgM
* Treponemal specific antibody (TPPH/TPHA)
* Non-treponemal antibody (VDRL, RPR)
* Expressed as dilution (1:16)
65
D
66
Blood cultures- meningeal/ pneumococcus, throat swab- niseria meningitidis, CSF- lumbar puncture, meningo and pneumo,
D- normally happens shouldn’t happen
67
C
68
D
69
B
70
B
Hep B E antigen test- marker of active or high risk antigen, if positive, more active Hep B, E antibody lower risk
* Surface antigen suggests acute infection
* Anti-surface antigen (Anti-Hbs positive) shows previous infection
* Anti-Hbc positive shows previous core
71
How do we classify bacteria?-
Stain them and look at them
72
What are gram positive cell walls made up of?
Cell wall made up of peptidoglycan and cell membrane
Appear dark purple- cell wall takes up the purple
73
What are gram negative cell walls made up of?
Negative= pink
Inner cell membrane, cell wall and then outer cell membrane. Outer prevents the dye from penetrating to the peptidoglycan- outer pink staining layer
74
What are the shapes of the gram positive and negative bacteria?
Cocci - In pairs, chains or groups
Rods - Groups, chains, solo
75
What is the appearence of gram positive and gram negative bacteria?
76
What do antibiotics work on?
* Cell Wall- interfere with cell wall synthesis
* Translation ( stop protein synthesis)
* Stop RNA synthesis
* Stop DNA replication
77
What are the antibiotics for cell wall?
B-lacterms- stop peptidoglycan in cell wall:
* Penicillins (amoxicillin, penicillin V)
* Cephalosporin (cefuroxime)
* Carbapenem (meropenem)
Glycopeptides (vancomycin)
78
What are the antibiotics for translation?
* Tetracyclin (doxycycline)
* Macrolides (erythromycin)
* Chloramphenicol
* Aminoglycosides (gentamycin)
79
What is the antibiotic to stop RNA synthesis?
Rifampicin
80
What is the antibioitic to stop DNA replication?
Quinolones (Ciprofloxacin)
Metronidazole
Anti-folates: Trimethoprim- Sulfa drugs
81
What are the mechanisms of drug resistance?
* Drug inactivation or modification
* Alteration of target
* Alteration of metabolic pathway
* Reduced drug accumulation
82
What happens when there is drug inactivation or modfication?
1)Drug inactivation or modification- bacteria produce an enzyme which destroys the antibiotic
Staph aureus – penicillinase, E. Coli - carbapenemase
83
What happens when there is alteration of target for drug resistance?
Alteration of target- or binding site
Staph aureus - Alteration of Penicillin binding protein so cannot bind to it
84
What happens when there is alteration of metabolic pathway for drug resistance?
Alteration of metabolic pathway
Sulfa resistant bacteria can use pre-formed folic acid
85
What happens when there is reduced drug accumulation relating to drug resistance?
Reduced drug accumulation- bacteria can express drug pump so that anitbiotics out of cell back into environment so not in the cell
Efflux pump – quinolones
86
Do beta lactams have gram positive or gram negative activity?
Most beta lactams have some gram positive and gram negative activity
87
What is amoxicillin used for?
Amoxicillin (beta lactam) is commonly used for ENT, respiratory and urinary infections
88
WHen there is resistance by bacteria what happens to amoxicillin?
Resistance by bacteria: β-lactamase breaks down β-lactams
89
What is co-amoxiclav made of? Why is it B lactamase stable?
Co-Amoxiclav = Amoxicillin + Clavulanic acid thus B lactamase stable
Co-amoxiclav is useful against beta-lactamase producers
Same concept: Tazocin = Piperacillin + Tazobactam
90
What does fluxcoacillin do?
Flucloxacillin – inhibits cell wall synthesis
91
What does flucloxacillin treat? What does it bind to?
* Only active vs gram positive bacteria
* Mainly used to treat Staph aureus infections
* Binds to penicillin binding protein
92
WHat is MRSA? What is it resistant against?
MRSA = methicillin (brother antibiotic to flucloxacillin) resistant S. aureus
Has mutation in penicillin binding protein – resistance to fluclox
93
What do you treat flucoxacillin with?
Have to use other antibiotic class such as Vancomycin
94
What is the narrowest spectrum of beta lactam and what is the broadest?
Penicillin (narrow spectrum) \< Cephalosporins (broad spectrum) \< Carbapenems (really broad spectrum)
Amoxicillin \< Cefuroxime \< Meropenem
95
What is pneumonia caused by? What is it sensitive to?
Most commonly caused by Streptococcus pneumoniae in the community which is sensitive to penicillin.
96
What is the score for pneumonia?
CURB65 score – how unwell the patient is
* C = confusion
* U = urea \<7
* R = resp rate \>30
* B = BP \<90/60
* 65 = aged over 65?
Risk stratification – how likely is the patient going to die from this infection?
97
What meds are given for high risk pneumonia?
High risk – co-amoxiclav + clarithromycin
98
What is given for low risk pneumonia?
Low risk – amoxicillin
99
What bacteria can form in gut flora due to broad spectrum antibiotics?
Use of broad spectrum antibiotics allows opportunity for C. diff infection as it kills bacteria in gut flora allowing few to overgrown such as C. diff
100
What type of bacteria is C diff?
which is a gram positive bacillus that produces toxins which leads to colitis.
101
What broad spectrum antibioitics can cause C diff?
Worst offenders for this opportunity – ciprofloxacin, cefuroxime, co-amoxiclav (usually names start with C and are broad spectrum)
102
Who is C diff most common in?
Elderly patients
103
What do you treat C diff. with?
Stop current antibiotics and start oral vancomyin- targets C diff
104
What are the symptoms for upper UTIs?
Upper – fever, loin pain, tachycardia, low BP
105
How do you treat upper UTIs?
treat with IV cefuroxime
106
What are the symptoms for lower UTIs?
Lower – dysuria, frequency
107
What is the treatment for lower UTIs?
nitrofurantoin, trimethoprim, pivmecillinam
108
What are UTIs most commonly caused by?
Most commonly caused by E. coli or other gram-negative bacilli
109
What is meningitis caused by in children and young adults?
Caused by Neisseria meningitides in children and young adults
110
What is meningitis caused by elderly patients?
Caused by Streptococcus pneumoniae in elderly patients
111
What do you treat meningitis with?
Treat with IV ceftriaxone until you know pathogen; use a good broad spectrum β-lactam.
112
If it is a CNS infection only what is it meningitis called?
Meningitis
113
If meninigitis in CNS and BS what is it called?
CNS and bloodstream infection = meningococcal septicaemia; blood has been affected by bug which is broken down to release toxins which accumulate and lead to powerful inflammatory response e.g. non-blanching rash, tachycardia, low BP
114
What is sepsis defined as?
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection - a body’s response to an infection injures its own tissues and organs.
115
What are symptoms of sepsis?
Main things to see drop in oxygen conc., impaired coagulation, increased bilirubin- liver system failure, low BP- failure of circulatory system, mental impairment with fall of GCS and renal impairment with rising chromatin and falling urine output
116
What is the acronym and managment of sepsis?
Management = BUFALO
B = blood cultures – 2 sets
U = urine output – catheterise to measure usually bad urine output
F = fluids – 500ml IV saline over 15 mins. Aim 30ml/kg in 1hr to resuscitate BP
A = antibiotics – as per suspected infection
L = lactate – ABGs for lactate and pH which shows underperfusion of patient
O = oxygen – 15 l/m via reservoir face mask
117
What is cellulitis caused by?
Skin and soft tissue infection (SSTI) caused by gram positive cocci –Staph aureus or Strep pyogenes.
118
What is cellulitis treated with?
Treated with flucloxacillin
119
What is necrotising fascitis?
Severe SSTI caused by a polymicrobial mix but usually involving Strep pyogenes
120
What is the treatment for necotising fascitis?
Treatment:
Debridement #1- cutting dead tissue away- no amount of antibiotics will sterilise dead flesh
Broad spectrum- Meropenem + clindamycin (covers organisms and anaerobes)
121
What is infective endocarditis?
Infection of heart valves
122
What is the cause of infective endocarditis?
Most common Staph aureus and Strep viridans; Treat using 6 week combo of IV antibiotics depending on cause
123
What antibiotics can be given for pregnancy?
Beta lactams are the most well tolerated antibiotics and safe in pregnancy: Penicillins & cephalosporins
124
What should you avoid to give during pregnancy?
Avoid or limited use in pregnancy:
* Quinolones (ciprofloxacin) – damage to cartilage
* Trimethoprim – folic acid antagonist- folic acid needed for DNA replication
* Tetracyclins – deposits and stains bones/teeth
Clinical pathology
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