Microbiology Flashcards

(368 cards)

1
Q

Mechanism of action of Antibiotics

A
Inhibit cell wall synthesis
------- β lactams(Penicillin, Cephlosporin, Carbapenems)
------- Glycopeptides (Vancoymycin, Teicoplanin)
Inhibit protein synthesis
------- Aminoglycosides (Gentamicin)
------- Tetracycline (Doxycycline)
------- Macrolide (Erythromycin)
------- Chloramphenicol
------- Oxazolidinones (Linezolid)
Inhibit DNA synthesis
------- Fluoquinolone (Ciprofloxacin)
------- Nitroimidazoles (Metronidazole)
Inhibit RNA synthesis
------- Rifamycin (Rifampacin)
Cell membrane toxin
------- Polymyxin (Colostin)
------- Cyclic lipopeptide (Daptomycin)
Inhibit folate metabolism
------- Sulfonamide (Sulphamethoxazole)
------- Diaminopyramidines (Trimethoprim)
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2
Q

Differences in cell structure in Gram +ve and Gram -ve

A

Gram +ve have thick peptidoglycan cell wall

Gram -ve have thin peptidoglycan cell wall + outer membrane

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3
Q

Inhibit cell wall synthesis

A
  • —– β lactams(Penicillin, Cephlosporin, Carbapenems)

- —– Glycopeptides (Vancoymycin, Teicoplanin)

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4
Q

Examples of βlactams

A
Penicillin
---- Benzylpenicillin
Cephalosporin
---- 3rd gen: Ceftriaxone, Cefotaxime, Ceftrazidime
---- 2nd gen: Cefuroxime
---- 1st gen: Cephalexin
Carbapenams
---- Meropenam
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5
Q

MOA of β lactams

A

Bind to penicillin-binding proteins –> ↓cell wall cross links –> weaker membrane –> lysed

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6
Q

Risk of cross-reactivity between βlactams

A

10%

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7
Q

Co-amoxiclav

A

Amoxicillin + Clavulanic acid

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8
Q

Tazocin =

A

Piperacillin (β lactam) + Tazobactam (β lactamase inhibitor)

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9
Q

With ↑generation of cephalosporin

A

↑Gram -ve cover, ↓Gram +ve cover

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10
Q

Why is Cef (cephalosporin) often given with Metronidazole

A

Met provides anerobe cover

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11
Q

ESBL stands for

A

Extended spectrum β-lactams

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12
Q

ESBL Tx

A

Carbapenam-sensitive

Resistant to Penicillin and Cephalosporins)

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13
Q

Carbapenemase

A

Resistant to Pencillin, Cephalosporin and Carbapenem

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14
Q

Inhibit protein synthesis

A

Inhibit protein synthesis (cATOM)

  • —— Aminoglycosides (Gentamicin)
  • —— Tetracycline (Doxycycline)
  • —— Macrolide (Erythromycin)
  • —— Chloramphenicol
  • —— Oxazolidinones (Linezolid)
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15
Q

Example of Glycopeptides

A

Vancomycin, Teicoplanin

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16
Q

MOA of Glycopeptides

A

Bind to enzymatic target (peptidoglycan precursors) –> weakened cell wall –> lyse
Similar MOA in β lactams bt bind to substrate (precursors)

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17
Q

Nephrotoxic ABx

A

Gentamicin, Amikacin (aminoglycosides)

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18
Q

Example of Aminoglycoside

A

Gentamicin, Amikacin, Tobramycin

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19
Q

MOA of Aminoglycosides

A

Aminoglycoside binds to 30S ribosomal subunit to prevent causing misreading of dcodons along the mRNA–> inhibits protein synthesis

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20
Q

Example of Tetracycline

A

Doxycycline

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21
Q

MOA of Tetracycline

A

Binds to 30S ribosomal subunit to prevent aminoacyl-tRNA binding –> inhibits protein synthesis

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22
Q

Example of Macrolide

A

Azithromycin, Clarithromycin

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23
Q

MOA of Macrolide

A

Binds to 50S ribsomal subunit –> prevents binding of peptidyl-tRNA

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24
Q

MOA of Chloramphenicol

A

Binds to 50S ribsomal subunit –> Prevents formation of peptide bonds

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25
Example of Oxazolidinone
Linezolid
26
Inhibit DNA synthesis
Inhibit DNA synthesis - ------ Fluoquinolone (Ciprofloxacin) - ------ Nitroimidazoles (Metronidazole)
27
MOA of Oxazolidinone
Binds to 23S component of 50S subunit to prevent formation of functional 70S initial complex
28
Example of Quinolone
Ciprofloxacin
29
MOA of Fluroquinolone
Bind to DNA gyrase --> inhibit DNA synthesis
30
Example of Nitroimidazole
Metronidazole, Nitrofurantoin (related)
31
MOA of Nitroimidazole
Under anerobic conditions, active intermediated is produced which causes DNA strand breakage
32
Inhibit RNA synthesis
Inhibit RNA synthesis | ------- Rifamycin (Rifampacin)
33
Example of Rifamycin
Rifampicin
34
MOA of Rifampicin
Binds to RNA polymerase --> inhibits initiation --> Inhibits RNA synthesis S/E organse secretions, Liver enzyme inducer
35
Cell membrane toxin
Cell membrane toxin - ------ Polymyxin (Colostin) - ------ Cyclic lipopeptide (Daptomycin)
36
Examples of cell membrane toxins + MOA
Daptomycin - inserts into cell membranes --> leak ions | Colistin --> unknown
37
Inhibit folate metabolism
Inhibit folate metabolism - ------ Sulfonamide (Sulphamethoxazole) - ------ Diaminopyramidines (Trimethoprim)
38
Example of Sulfonamide + MOA
Sulphmethoxazole --> interferes with folate metabolism
39
Example of Diaminopyrimidine + MOA
Trimethoprim --> interferes with folate metabolism
40
Co-trimoxazole =
Sulphamethoxazole + Trimethoprim
41
Mechanisms of ABx resistance
BEAT drug action - Bypass ABx sensitive step in pathway (Trimethoprim) - Enzymatic drug inactivation (β lactamase) - ↓ Accumulation of drug (Tetracycline resistance) - ↓ uptake or efflux - change drug Target (MRSA, Quinolone resistance)
42
β-lactamases - types, act against
Breaks down β lactams - β-lactamase (against Penicillin) - ESBL (against cephalosporins) - AmpC (against cephalosporins, not inhibited by Clavulanic acid) - Carbapenemase (against all β lactams)
43
MRSA - resistance mechanism
Altered target (mecA gene encodes novel PBP called PBP-2a)
44
Abx for ESBL
β-lactam + Aminglyocoside (Gentamicin, Amikasin)
45
ABx for MRSA
Vancomycin (or Linezolid)
46
Abx for C diff
Metronidazole (or Vancomycin)
47
Abx for Chlamydia
Doxycycline
48
ABx for bacterial conjunctivitis
Chloramphenicol
49
ABx for VRE
Linezolid | Daptomycin
50
Cover for anerobes
Metronidazole
51
ABx fo PCP
Co-trimoxazole = Trimethoprim + Sulphamethoxazole
52
ABx for UTI
Trimethoprim or Nitrofurantoin
53
ABx for Hospital UTI
Augmentin (or Cephalexin)
54
ABx for pseudomonas
Gentamicin, or Tazocin
55
Main ABx for S aureus
Flucluoxacillin
56
Main ABx for Skin infections
Flucluoxacillin +/- Vancomycin (if MRSA)
57
Main ABx for meningitis
Ceftriaxone +/- Amoxicillin (listeria cover)
58
ABx for pharyngitis
Benzylpenicillin (cover Group A strep)
59
ABx for CAP (mild)
Amoxicillin (cover Strep pneumoniae + Hib)
60
ABx for CAP (severe)
Co-amoxiclav + Clarithromycin
61
ABx for HAP
Amoxicillin + Gentamicin OR Tazocin
62
Abx for E. coli
Gentamicin
63
Define minimum inhibitory concentration
Least amount of drug required to inhibit growth of organism in culture Assessed using agara disc diffusion (calculate from boundary of growing + inhibited growth)
64
Empirical ABx therapy
Use BSABx which is likely to cover the likely organisms | Then change based on culture sults to ↑ specific/narrow agent
65
Pharmacokinetic/Pharmacodynamic ideal for Gentamicin
Peak above MIC (Cmax)
66
Pharmacokinetic/Pharmacodynamic ideal for Penicillin
Time above MIC
67
Causes of secretory diarrhoea (profuse, watery diarrhoea)
``` Vibrio cholera E coli (ETEC, ERPC, EHEC) ```
68
Causes of inflammatory diarrhoea (neutrophil in stools)
Campylobacter Shigella Salmonella (non-typhoidal) EIEC
69
Causes of enteric fever (lymphocytes in stool)
Salmonella (typhoidal) Yersinia spp Brucella
70
Staphylococcus aureus
Aetiology: Pre-formed enterotoxin (exotoxin) --> superAg in GIT Sx: Diarrhoea (non-bloody) and Vomiting <6 hr incubation Micro: Catalase +ve, Coagulase +ve, Gram +ve coccus, Clusters/Clonies, Protein A, β haemolytic on blood agar Self-limiting
71
Bacillus cereus
``` Reheated rice --> spre germinate Microscopy: spore-forming Gram +ve rod Aetiology: Heat stable emetic toxin (remains after heating) + Heat labile diarrhoeal toxin (can be destroyed by heating) Sx: Watery diarrhoea (non-bloody) <6hr incubation Self-limiting ```
72
Clostridia botulinum
Gram +ve anaerobe Canned/Vacuum packed food Preformed toxin INACTIVATED by cooking (blocks Ach release from nerves) Tx: Antitoxin
73
Clostrdia perfringens
Gram +ve anaerobe Reheated meat Watery diarrhoea +/- Vomiting (24 hours) Incubation 8-16 hours
74
Clostridia difficile
``` Gram +ve anaerobe 2 toxins (A, B) Associated with ABx Ix: Pseudomembranous colitis Tx: (1) Metronidazole, Infection control (2) Vancomycin ```
75
Listeria monocytogenes
Outbreaks of febrile gastroneteritis Refrigerated food, Unpasteruised diary, Vegetables Microscopy: β-haemolytic, aesculin +ve, tumbling motility Sx: Watery diarrhoea, Fever, Vomiting Tx: Ampicillin or Ceftriaxone
76
Types of E coli
``` Diarrhoea +/- bloody (if haemorrhagic form) Faecal-ortal route Self limiting - ETEC - EIEC - EHEC - EPEC ```
77
ETEC
Toxigenic --> traveller's diarrhoea
78
EIEC
Invasive dysentery
79
EHEC
Haemorrhage (shiga-like verocytotoxin) (Haemorrhagic 0157)
80
EPEC
Infantile diarrhoea (Paeds)
81
Salmonella typhi / paratyphi (enteric fever)
``` Constipation (slow onset) Rose spots Splenomegaly Anaemia, Leukopenia Fever Blood culture +ve Multiples in Peyer's patches Tx: Ceftriaxone ```
82
Salmonella enteritidis
Poultry, Eggs, Meat Diarrhoea (non-bloody) Self-limiting
83
Shigella
Shiga toxin --> affects distal ileum/colon Fever Bloody diarrhoea Tx: avoid ABx
84
Vibrio cholerae
Rice water stool (with no inflammatory cells) Enterotoxin A and B Water contaminated with huan faeces Tx: supportive
85
Vibrio parahaemolyticus
Raw undercooked seafood (in Japan) Diarrhoea Self-limiting Tx: Doxycycline
86
Vibrio vulnificus
Water-bourne organism Shellfish handler / Scuba diver Fetal sepsis with D&V in HIV patients Tx: Doxycycline
87
Campylobacter jejuni
``` Upasteurised milk, poultry Prodrome of headache + fever Bloody diarrhoea (foul smelling) Cx - GBS - Reactive arthritis Tx: Erythromycin ```
88
Yersinia enterocolitis
``` Food contaminated with animal faeces Prefers cold environment (4o) Enterocolitis Mesenteric adenitis Cx - Reactive arthritis - Erythema nodosum ```
89
Mycobacteria
HIV patients | Diarrhoea
90
Entamoeba histolytica
``` Mobile trophozoite found in diarrhoea MSM Food, water, soil Non-motile cyst in non-diarrhoea illness Histology: flask shaped ulcer Dysentery Flatuence Tenesmus Chronic weight loss Liver abscess Tx: Metronidazole ```
91
Giardia lamblia
Pear shaped trophozoite Traveller / Hiker / MSM / Mental hospital Ingesting cysts from faceally contaminated water Non-bloody diarrhoea (foul smelling) Flatulence ELISA string test: string attached to ingested capules --> fished out Tx: Metronidazole
92
Cryptosporidium parvum
Swimming Oocysts seen in stool by modified Kinyoun acid fast stain Severe diarrhoea in immunocompromised
93
Norovirus
Outbreaks D&V Cruse ships
94
Rotavirus
< 6 years old
95
Adenovirus
Type 40+41 --> non-blood diarrhoea < 2 year olds Immunocompromised
96
DDx Bloody diarrhoea
Shigella Campylobacter E coli
97
Hepatitis A transmission
Faecal-oral route (infected water) | RNA virus
98
Hepatitis A Serology
Anti-HAV IgM = recent infection | Anti-HAV = previous infection or vaccine
99
Hepatitis A disease course
↑ ALT, ↑ IgM | Later, ↑ IgG
100
Hepatitis A - Tx
Supportive only
101
Hepatitis B - route of infection
dsDNA virus Sexual Vertical Blood / needlestick
102
Hepatitis B - Ix
↑ ↑ ALT, ↑ AST HBsAG (infection or vaccine) HbcAb (acute IgM, chronic IgG)
103
Hepatitis B - Tx
PegIFN- α2a (direct anti-viral effect, upregulates MHC) Tenofovir (RT inhibitor) Lamivudine (inhibits viral polymerase) Entecavir (inhibits viral polymerase)
104
Hepatitis C - route of infection
RNA virus | Blood products
105
Hepatitis C - Ix
ALT | Anti-HCV
106
Hepatitis C - Tx
PEG-IFN- α2b | Ribavirin
107
Hepatitis D
Only infect Hepatitis B +ve patients | Ix: IgM anti-HDV
108
Hepatitis E
RNA virus Faecal-oral transmission India Tx: Supportive
109
Complications of Hepatitis B / C
Hepatitis --> Fibrosis --> Cirrhosis --> Cancer ↑ risk of Hepatocellular carcinoma Liver transplant
110
uncomplicated vs complicated UTI
Complicated UTI has functional or structural abnormality (including: male, pregnancy, children, hospitalised)
111
Most common cause of UTI
E coli
112
Non E coli organisms causing UTI
``` Proteus mirabilis Klebsiella aerogenes Enterococcus faecalis Staphylococcus saprophyticus - only non-E-coli organism causing UTI in normal urinary stem Staphylococcus epidermis ```
113
Routes of UTI
Ascending UTI or Haematogenous route (bacteraemia, endocarditis)
114
+ve nitrite indicates
Likely UTI
115
-ve nitrite AND +ve leukocyte
Urine culture | Treat if symptomatic
116
Nitrites are specific for
Coliform bacteria (have a reducing enzyme converting nitrates --> nitrites)
117
Urine leucocytes indicate
Inflammation
118
Definition of UTI
> 10,000 CFU / ml + urinary symptoms
119
DDx sterile pyruia
Chlamydia, TB
120
Urine microscopy showing squamous cells
Perineal contamination
121
Treatment of UTI
Trimethoprim or Nitrofurantoin
122
Treatment of Pyelonephritis
Co-amoxiclav +/- Aminoglycoside (Gentamicin)
123
Tx of complicated UTI (pregnancy, male)
Cefalexin or Co-amoxiclav
124
Candida UTI is associated with
Indwelling catheter | Tx: removal will cure
125
CSF: ↑ WBC polymorphs, ↑↑ protein, ↓ glucose, turbid CSF
Bacterial meningitis
126
CSF: ↑ WBC lmphocytes, ↑/ protein, glucose
Viral meningitis
127
CSF: ↑ WBC lymphocytes, ↑↑ Protein, ↓ Glucose
TB meningitis
128
Meningitis, Gram +ve diplococci, α-haemolysis
Streptococcus pneumoniae
129
Meningitis, Gram -ve diplococci
Neisseria meningitidis
130
Meningitis, Gram +ve rods
Listera monocytogenes
131
India ink stain, MSM
Cryptococcus
132
Meningitis organisms
Neisseria meningitidis (Gram -ve diplococci) Streptococcus pneumoniae (Gram +ve diplococci) In neonates ---- GBS ---- Listeria ---- E coli TB Viral: Coxsackie, Mumps, HSV2 Fungal: cryptococcus
133
Tx for meningitis
IV Ceftriaxone
134
Tx for encephalitis
IV Aciclovir
135
Define Hospital acquired infection
infection > 48 hr of admission, 3 days discharge of 30 days of surgery, not present on admission
136
How common are HAI?
8%
137
Most common HAI
Hospital-acquired pneumonia
138
C. difficile - Gram, RF, Ix, Tx
Gram +ve, spore-forming anerobe Risk factors: ABx Ix: Pseudomembranous colitis Tx: Metronidazole
139
E. coli - Gram
Gram -ve rod | Resistant to β-lactamases
140
Surgical site infection organisms
MRSA | Coagulase -ve Staphylococcus
141
Water-associated organisms
Legionella Pseudomonas Mycobacteria
142
Most common pathogens involved in surgical site infections
S aureus (MSSA, MRSA) Less common - E coli - Pseudomonas
143
Tx for surgical site infection
Flucluoxacillin
144
Septic arthritis - organisms
Staph aureus (46%) Streptococci (22%) Less common: E coli
145
Septic arthritis - Sx
Fever Red, hot, swollen joint Unable to weight bear
146
Septic arthritis risk factors
RhA | OA | IVDU | DM | Immunosupression | Trauma | S aureus strain --> produces Panton-Valentine Leucocidin (PVL)
147
Septic arthritis - Ix
Blood culture Joint aspirate > 50,000 WBC/mm3 ESR, CRP Imaging: effusion
148
Osteomyelitis organisms
``` S aureus (48%) Less common: Gram -ve rods, Streptococcus ```
149
Osteomyelitis - Ix for diagnosis
MRI - best imaging | Bone biopsy for culture/histology
150
Osteomyelitis
ABx +/- debridement
151
Prosthetic joint infection - organisms
Coagulase -ve Staph = Staphylococcus epidermidis ( > Staph aureus) Streptococci spp. Enterococci spp
152
Prosthetic joint infection - Sx
Pain Joint was 'never right' since operation Early failure of jiont
153
Prosthetic joint infection - Ix
X-ray: "Loosening" | Joint aspirate
154
Prosthetic joint infection - Tx
Remove metalwork | Joint replacement
155
Classical causes of Pneumonia
``` Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis Staphylococcus aureus Klebsiella pneumoniae ```
156
Most common cause of CAP
Streptococcus pneumoniae
157
Streptococcus pneumoniae
Gram +ve diplococci (α haemolysis) Rusty coloured sputum Lobar pneumonia
158
Haemophilus influenzae
Gram -ve cocco-bacilli Smoking Pre-existing lung disaese (e.g. COPD) Chocolate agar plate
159
Moraxella catarrhalis
Gram -ve coccus | Smoking
160
Staphylococcus aureus
Gram +ve cocci - "grape-bunch clusters" Recent viral infection CXR: cavitation
161
Klebsiella pneumoniae
Gram -ve rod (enterobacter) Alcoholics Elderly Haemoptysis
162
Classical vs Atypical pneumonia - presentation
Classical - signs on chest exam + CXR Atypical has NO signs on chest exam and normal CXR +/- extrapulmonary features (e.g. ↓ Na+) + do not respond to β lactams
163
Causes of atypical pneumonia
``` Legionella pneumophila Mycoplasma pneumonia Chlamydia pneumonia Coxiella burnetii (Q fever) Chlamydia psittaci (Psittacosis) Bordatella pertussis TB ```
164
Legionella pneumophila
``` Water (air conditioning) / Travel Hyponatraemia Hepatitis ↓ WBC Confusion Diarrhoea Ix: Urinary legionella antigens Charcoal agar ```
165
Mycoplasma pneumonia
``` Epidemics (every 5 years) Cold agglutinin test Erythema multiforme Risk of SJS Autoimmune haemolytic anaemia Joint pain ```
166
Chlamydia pneumonia
#NAME?
167
Coxiella burnetii (Q fever)
Farm animal: Goat / Sheep / Cattle --> aerollised / infected milk
168
Chlamydia psittaci (Psittacosis)
Birds
169
Bordatella pertussis
Whooping cough | Unvaccinated (travelling community)
170
TB
Poor response to ABx Auramine-Rhodamine stain Ziehl-Neelson stain
171
Ix for pneumonia
``` CURB-65 score > 2 warrants admission Confusion Urea > 7 RR > 30 BP < 90 Age > 65 years old ```
172
Bronchitis vs Pneumonia
``` Bronchitis = inflammation of medium sized airways Pneumonia = inflammation of alveoli ```
173
Bronchitis - organisms
Viruses Streptococcus pneumoniae H. influenzae Moraxella catarrhalis
174
Bronchitis - Tx
Bronchodilation, Physiotherapy
175
Causes of cavitation on CXR
Staphylococcus aureus Klebsiella pneumoniae TB Haemophilius influenzae
176
Hospital acquired pneumoniae organisms
``` Gram -ve ---- E coli ---- Klebsiella ---- Pseudomonas Staph aureus Fungi Protozoa ---- Pneumocystis jirovecii ```
177
Pneumocystis jirovecii
``` Protozoan Immunosupressed Silver stain Immunofluorescence AIDS-defining illness CXR: "bat's wing" or "bilateral ground glass shadowing" Ix: Walkings sats test (definitive test for PCP) Tx: Co-trimoxazole ```
178
Aspergillus fumigatus
``` MC+S: Hypae with flower heads Allergic bronchopulmonary aspergillosis --- Chronic wheeze --- Eosinophilia Aspergilloma --- In pre-existing cavity Invasive aspergillosis --- Immunocompromised ```
179
HIV with LRTI
PCP, TB, atypical mycobacteria
180
Neutropenia with LRTI
Fungi (aspergillius)
181
Bone marrow transplant with LRTI
CMV
182
Splenectomy with LRTI
Encapsulated organisms (N meningitis, H influenzae, S pneumoniae)
183
Cystic fibrosis with LRTI
Pseudomonas aeruginosa, Burkholderia cepacia
184
Tx for CAP (mild)
Amoxicillin OR Macrolide (Clarithromycin / Erythromycin)
185
Tx for CAP (severe)
Co-amoxiclav AND Macrolide (Clarithromycin)
186
Tx for atypical pnemonia
Macrolide
187
Tx for HAP
Ciprofloxacin +/- Vancomycin
188
Tx for MRSA
Vancomycin
189
Tx for pseudomonas
Tazocin OR Ciprofloxacin +/- Gentamicin
190
Tx for aspiration pneumonia
Cefuroxime + Metronidazole (need Gram +ve, -ve and anaerobic cover)
191
Tx for Legionella
Macrolide + Rifampicin
192
Tx for S aureus
Flucloxacillin
193
Slow growing mycobacteria
``` MTB complex ---- M bovis (cows, BCG vaccine) ---- M tuberculosis ---- M africanum (West Africa) ---- M marinum (swimming pool granuloma), aquarium owners, plaques/papules ---- M ulcerans (chronic painless ulcer) M avium complex ---- M avium ---- M avium intracellulare (invades bronchial tree in those with prexisting lung disease, children with pharyngitis) ```
194
Rapidly growing mycobacteria
M abscessus complex --> skin/soft tissue infection
195
Ungrouped mycobacteria
M leprae --> Leprosy (spectrum from few skin lesion to multiple skin lesions with profound disfigurement and nerve damage) - Depigmentation, Macules, Plaques, Nodules, Ulcers - Sensory neuropathy - Keratitis - Periositis aseptic necrosis
196
Stain for mycobacteria
Acid fast bacilli Auramine-Rhodamine stain: fluorescent AFBs Ziehl-Neelsen stain
197
Non-TB bacteria commonly found in
Water and Soil (in nature) | No person to person transmission
198
Vaccination against TB
Bacille Calmette-Guerin (BCG) = live attenuated M. bovis strain
199
TB is associated with
``` Erythema nodosum Pulmonary TB: Caseating granuloma Lymphadenitis (scrofula) GI TB Peritoneal TB (ascites) GU TB (sterile pyruia) Spinal TB = Pott's disease (+/- Iliopsoas abscess) Meningeal TB Miliary TB (millet seeds on CXR) ```
200
Histology of TB
Caseating granuloma
201
Culture for TB
Lowenstein-Jense (LJ) medium (gold standard)
202
Ix for speciation / drug resistance of TB
NAAT / PCR
203
Tuberculin skin test +ve
Latent TB, Active TB or Vaccination
204
IGRA = interferon γ release assay = ELISpot = Quantiferon
+ve in Latent TB and aactive TB
205
S/E of TB treatment
Rifampicin - orange secretions, liver enzyme inducer Isoniazid - peripheral neuropathy (Tx: Vitamin B6 / Pyridoxine) Pyrazinamide - Hepatotoxic Ethambutol - loss of colour vision, optic neuritis Risk of immune reconstitution inflammatory syndrome (IRIS) in HIV patients
206
% of world infected with TB
30%
207
Risk of reactivation of latnet TB
10% lifetime risk | If HIV +ve --> this increases to 10% yearly risk
208
Road to pandemic
Acquire mutations to break down species barrier / cross-over into humans ---- PB2 switch ---- Reassortment = ANTIGENIC SHIFT (co-infection between Bird flu and human flu --> viral proteins recombine --> allow infection of humans) ---- ANTIGENIC DRIFT = mutation in HA/NA to give new strains Survive longer in environment (remain airbounr in mildly acidic resp droplets Overcome barriers to infection (physical, chemical, receptor)
209
Natural reservoir for Influenza A
Ducks
210
Respiratory tropism is the result of
Influenza virus requires activation by host cell proteases only expressed in respiratory tract
211
Infection by influenza
Attachment to sialic acid cell surface receptor --> endosome --> release viral DNA HA must be cleaved for viral fusion to occur (airway tryptase only found in the lung) Viral DNA to nucleus --> mRNA synthesis --> viral proteins --> virus buds off
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Most common cause of death from pandemics
Cytokine storm (hypercytokinaemia) --> acute respiratory distress syndrome --> pulmonary oedema --> death
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Influenza virus - number of genetic segments
8 RNA segments Encodes for - Neuraminidase (NA): cleaves sialic acid residues --> exposures receptors on host cell, disrupts mucus barrier - Haemogglutinin (HA): binds sialic acid receptors --> viral entry (named for causing agglutination fo RBCs)
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Anti-virals for Influenza
Amantadine: targets M2 ion channel, most viruses already resistant Oseltamavir (Tamiflu): neuraminidase inhibitor Zanamivir (Relenxa) (Favipiravir, Baloxavir): polymerase inhibitors [NEW] Sialic acid
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Recent change in vaccination strategy since 2009 pandemic
Vaccinate children (intranasal flu vaccine) with live attenuated virus Vaccinate healthcare works Vaccinate elderly
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Link between Pandemic and Seasonal flu
Pandemics may drift and transform into seasonal influenza
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3 seasonal flus
``` Influenza A (H1) - peaks in Jan Influenza A (H1N1) - peaks in Dec Influenza B (peaks in March) ```
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Most common cause of meningococcal disease in the UK
MenB | MenC / Hib / Pneumococcus now rare as vaccainated against
219
TORCH screen
``` Toxoplasmosis Other - Syphilis, HIV, Hepatitis B/C Rubella CMV Herpes ```
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TORCH infection - Sx
``` Thrombocytopaenia Other (cataracts, choroidoretinitis) Rash Cerebral abnormality (microcephaly) Hepatosplenomegaly ```
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Toxmoplasmosis
``` Cats --> Mice/Birds Cat litter Asympatomatic at birth (60%) 40% symptomatic - Choroidoretinitis - Microcephaly Long term: deafness, ↓ IQ ```
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Congenital Rubella syndrome
Only risk if < 20 weeks' gestation | Triad of cataracts, sensorineural deafness, congenital heart defects
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HSV
Lies in mother's genital tracts | Congenital HSV - blistering rash, disseminated HSV, meningoencephalitis
224
Early vs Late onset neonatal infection =
Early < 48 hours since birth | Late > 48 hours since birth
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Group B strep
Gram +ve coccus Catalase -ve β-haemolytic
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E coli
Gram -ve rod
227
Listeria monocytogenes
Gram +ve rod
228
Risk factors for early onset neonatal sepsis
PROM | PPROM | Chorioamniotis | Meconium staining | Acidosis | Hypoglycaemia | Jaundice
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Early onset neonatal sepsis - organisms
GBS - most common E coli Listeria monocytogenes
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Early onset neonatal sepsis - Tx
benzylpenicillin (covers GBS + Listeria) + Gentamicin (covers E coli)
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Late onset neonatal sepsis - organisms
Coagulase -ve Staphylococci GBS | E coli | Listeria S aureus Gram -ve (Klebsiella, Enterobactera | Pseudomonas)
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Late onset neonatal sepsis - Tx
Cefotaxime + Vancomycin
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Neisseria meningitidis
Gram -ve diplococci
234
Streptococcus pneumoniae
Gram +ve diplococus, α-haemolytic, optochin sensitive
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Haemophlius influenzae
Gram -ve rod, Chocolate agar (grows on haemolysed blood)/
236
Meningitis organisms based on age
< 3 months: GBS, E coli, Listeria, N meningitis, S pneumoniae, Hib if unvaccinated > 3 months: N meningitis, S pneumoniae, Hib if unvaccinated > 6 years: N meningitis, S pneumoniae
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Respiratory infection organisms in children
Viruses Then, S pneumoniae Then, Mycoplasma (>4yr)
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Ix for ? Rubella infection in mothers
``` Look for evidence of seroconveresion Rubella IgM as marker of infection PCR - gold standard (respiratory seretions, blood, urine) Tx: < 20 weeks --> TOP No documented risk > 20 weeks' gestation ```
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Congenital CMV - Ix
Prenatal Ix: amniocentesis PCR, cell culture, DEAFF (cell culture), Serology (IgM, IgG) Post-natal: urine + saliva swabs (CMV is shed in urine and saliva)
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Congenital CMV - Tx
Valganciclovir or Ganciclovir
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Congenital CMV - SX
90% asympatomatic at birth (10% will become symptomatic) | 10% symptomatic at birth - hearing loss, microcephaly, choroidoretinitis, jaundice
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HSV infection has highest risk when
In 6 weeks before EDD ∴C-section is recommended
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Congenital HSV infection - Sx
Skin, Eye, Mouth disease - scarring, hypopigmentation CNS disease - microcephaly Disseminated infection
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Congenital HSV - Tx
IV Aciclovir
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VZV in early gestation cause
Congenital varicella syndrome
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VZV in late gestation lcauses
Neonatal varicella syndrome
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Tx for VZV exposure
VZIG within 10 days of exposure | Aciclovir if > 10 days post-exposure
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Measles infection in pregnancy
↑ risk of miscarriage | No congenital measles syndrome
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Parvovirus in pregnancy - Sx
``` Slapped cheek syndrome Aplastic crisis Hydrops foetalis Tx: intrauterine transfusion No risk > 20 weeks gestation ```
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Congenital Zika syndrome
Microcephaly Seizures Retinopathy, Deafness
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Tx for HSV and VZV
(1) Aciclovir (2) Valaciclovir (prodrug of AC) (3) Famciclovir Act Very Fast! (2nd line) = Foscarnet or Cidofovir
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MOA of Aciclovir
Guanosine analogue --> activated by viral thymidine kinase --> ACP-PPP --> binds to viral DNA polymerase
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CMV - Histology
Owl's eye inclusions
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CMV - Sx
Bone marrow suppression Retinitis Pneumonitis
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CMV - Tx
(1) Ganciclovir (2) Foscarnet (3) Cidofovir Different as CMV does not have same enzymes
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MOA of Gancliclovir
Requires activation by viral UL97 kinase Inhibits viral DNA synthesis S/E: BM supression
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MOA of Foscarnet
Non-competitive inhibitor of viral DNA polymerase (does not require activation)
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MOA of Cidofovir
Nucleoside analogue -> competitive inhibitor of viral DNA synthesis
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MOA of Miribavir
Inhibits viral kinase
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MOA of Letermovir
CMV DNA terminase inhibitor
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EBV infects
B cells (lifelong low grade viral replcication)
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EBV is associated with
Post-transplant lymphoproliferative disease --> classical HL, Burkitt's lymphoma - Latently infected B cells --> polyclonal activation Tx: ↓ immunosuppression, Rituximab (Anti-CD20 Ab)"
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Tx for Bronchiolitis (RSV)
Ribavirn (Guanosine analogue --> inhibit viral RNA synthesis) IVIG
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Prophylaxis for Bronchiolitis (RSV)
Palivizumab (mAb against RSV)
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BK virus - Sx
Only sympatomtic in immunocompromised - In bone marrow transplant --> Haemorrhagic cystitis (Tx: Cidofovir) - In renal transplant --> BK nephritis (Tx: IVIG)
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Most common cause of HSV drug resistance to ACV
Mutation in viral thymidine kinase | Tx: Foscarnet
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Most common cause of CMV drug resistance to GCV
Mutation in protein kinase gene (UL97) | Tx: Foscarnet
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Indications for treating chickenpox
Immunocompromised, Pregnant, Adults with pneumonitis
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Basic reproductive rate (R0)
Average number of individuals infected by infectious case during their infectious period If R0 < 1 --> transmission is stopped
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Herd immunity threshold (HIT)
= 1 - (1/R0) | Percentage required to stop the spread of disease
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Inactivated vaccine
Pathogen destroyed by heat, chemicals, radiation or ABx Unable to cause infection e.g. Influenza, Polio
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Attenuated vaccine
Live organisms grow in un-natural host --> less virulent Risk of reversion to virulence Contraindicated in pregnancy and immunosuppressed patients e.g. MMR
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Toxoid vaccines
Inactivated toxic component | e.g. Tetanus, Diphtheria
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Subunit vaccine
Protein component of pathogen | e.g. Hepatitis B, HPV
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Conjugate vaccine
Poorly immunogenic antigen with adjuvant | e.g. Hib
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Heterotypic vaccines
Pathogens that infect other animals but only cause mild disease in humans e.g. BCG
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Contraindications for influenza vaccine
Anaphylactic hypersensitivity to egg
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Contraindications for MMR
Immunocompromised, Pregnant, Anaphylactic reaction to egg
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HIV fusion inhibitor
Enfuvirtide
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CCR5 co-receptor antagonist
Maraviroc
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NRTI
Zidovudine, Tenofovir
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NNRTI
Efavirenz
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Integrase inhibitor
Raltegravir
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Protease inhibitor
Ritonavir
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Yeast vs Mould
Yeast = individual cells (divide by budding from one another) ---- Candida ---- Cryptococcus Mould = filamentous fungi ---- Aspergillus ---- Dermatophytes N.B. Dimorphism (yest during infection, mould in nature)
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Fungal - superficial vs deep (definition, Ix)
Superficial (skin, hair, nails) vs Deep (systemic) Ix for superficial - Woods Lamp for diagnosis (Tinea, Pityriasis) Ix for deep - clinical Hx, Ix, Imaging for diagnosis (Candida, Aspergillus)
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Types of Candida
Candida albicans Candida glabrata - resistant to 1st line azoles Candida krusei - resistant to 1st line azoles Candida tropicalis Candida dubliniensis
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Candida microscopy
``` Discrete colonies Germ tubes (indicates likely C albicans) ```
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Candida culture
Chromogenic agar MALDI-TOF technique Sabouraud's dextrose agar
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Candida - Ix
Microscopy Blood cultures - candidaemia Serology - β-D-Glucan assay
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Candida - Tx
Echinocandin (anidulafungin) - covers C albicans + non-albicans +/- Fluconazole - covers C albicans
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Cryptococcus types
Cryptococcus neoformans Cryptococcus gattii Cryptococcus life cycle between Bird excrement and Eucalyptus trees Often affects immunocompromised (esp HIV)
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Cryptococcus - Ix
India Ink staining --> Halo appearance ---- capsule protects cryptotoccus from being stained black Enzyme immunoassay for Cryptoccocal antigen (gold standard) CXR: pulmonary cryptococcoma
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Cryptococcus - Tx
Amphotericin B
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Aspergillus - microscopy
Filaments Hyphae Spores
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Aspergillus types
``` Aspergillus fumigatus Aspergillus flavus Aspergillus niger Aspergillus nidulans Aspergillus terreus ```
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Aspergillus - Sx
Mycotoxicosis - ingestion ABPA Aspergilloma Invasive aspergillosis
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Aspergillus - risk factor
Building work
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Aspergillus - Ix
Microscopy - mainstay of Dx Culture Galactomannan Ag Aspergillus PCR
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Aspergillus - Tx
Amphotericin
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Dermatophtes
``` Tinea pedia Tinea cruris (groin area) Tinea corporis (ringworm) Tinea capitis (scalp) Onychomycosis Pityriasis versicolour - discolouration of skin (malassezia furfur) ```
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Mucormycosis - Sx + Tx
Black eschar (black pus) Due to Rhizopus spp, Rhizomucar spp, Mucor spp Tx: Surgical debridement + Amphotericin
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Types of anti-fungals
``` Cell membrane anti-fungals ---- Azoles (Ketoconazole) ---- Polyene (Amphotericin B) DNA synthesis anti-fungals ---- Flucytosine Cell wall antifungals ---- Echinocandin (caspofungin) ```
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MOA of Azoles
Affects cell membrane synthesis Bind to lanosterol 14 α demethylase --> prevents conversion of lanosterol to ergosterol --> build up of toxic sterol --> cell death
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MOA of Polyenes
Affects cell membrane integrity | Forms transmembrane channels in fungal cell wall --> electrolyte leaks --> cell death
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MOA of Flucytosine (DNA synthesis antifungal)
Inhibits DNA synthesis in fungal cells
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MOA of Echinocandin (Caspofungin)
Affects cell WALL | Inhibits β (1,3) D-glucan synthase --> loss of cell wall glucan --> osmotic fragility --> lysis
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Pyrexia of unknown origin
Fever > 38.3 lasting > 3 weeks without diagnosis OR uncertain diagnosis after 7 days in hospital OR after sensible set of Ix
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Durack and Street criteria for PUO
``` Classical PUO: PUO after > 3 days in hospital - Infection - Malignancy - Connective tissue disorders Healthcare-associated PUO: PUO after 24 hours in hospital - Surgery - Drugs - Medical devices - LRTI Neutropenic PUO: Fever with neutropenia (medical emergency) - Chemotherapy - Haematology malignancy HIV-associated PUO: HIV +ve patient with PUO - Seroconversion - TB - Kaposi's sarcoma ```
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Routine Ix for PUO
``` FBC, U&E, Protein, LFTs, CRP HIV test Blood culture x3 Urine culture CXR ```
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Criteria for bacterial endocarditis
Duke's criteria
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Macrophage activation syndrome
Associated with systemic-onset juvenile idiopathic arthritis Sx: Fever, hepatosplenomegaly, pancytopenia, ↑ IFN-γ, GM-CSF ↓ Hb, ↓ Plt, ↓ Neutrophils
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DDx Fever with Rash
``` Dengue Chikungunya Rickettsial Enteric fever (rose spots) Measles ```
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DDx Fever with haemorrhage
Viral haemorrhagic fever (Dengue) | Meningococcaemia
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DDx with Eosinophlia
Acute schistosomiasis, Drug hypersensitivity
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DDx Fever with onset > 6 weeks after travel
Malarix vivax Acute hepatitis Amoebic liver abscess
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Types of malaria
Protozoa, Anopheles mosquito - P falciparum - P vivax - P ovale - P malariae - P knowlesi
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Malaria Sx
``` Cyclical fever Severe when parasitaemia > 2% - Altered consciousness - Metabolic acidosis - Haemoglobinuria --> black water fever - Anaemia - Jaundice - Coagulopathy ```
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Malaria - Ix
Thick blood film --> screen for parasites Thin blood film --> identification of species ---- Falciparum is typically headphone shaped (cresent shaped) and RBCs have >1 intracellular parasite Giemsa stain
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Malaria - Tx
Non-falciparum malaria --> Chloroquine, Primaquine (if G6PD normal) Falciparum malaria - Mild --> Atovaquone, Proguanil, Riamet (Artemisinin + Lumefantrine), Quinine - Severe --> IV Artesunate
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Dengue fever - Sx
Fever Sunburn-appearing rash - blanching Tourniquet test +ve (mark left where skin was squeezed) Retro-orbital headache
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Dengue fever - Ix
Dengue PCR | Serology IgM +ve
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Chikungunya virus
↑arthralgia (c.w. dengue)
324
Enteric fever = Typhoid fever
``` Salmonella typhi / paratyphi High, prolonged fever Rose spots Constipation Tx: IV Ceftriaxone + Azithromycin ```
325
Infectiuos mononucleosis
EBV or CMV Fever Tonsillitis Ix: atypical lymphocytosis, monospot test
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Campylobacter jejuni
Gram -ve rod Chicken Sx: Diarrhoea Ix: Stool MC&S
327
Salmonella
Gram -ve rod Chicken, contaminated food, poor hand hygiene India Salmonella typhi/paratyphi --> enteric fever (rose spots, constipation) Other strains --> enteritis
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Bartonella henselae
Gram -ve rod Cat scratches Cat scratch disease (immunocompetent) --> Macule, Fever, Night sweats,Weight loss Bacilliary angiomatosis (immunocompromised) --> Skin papules, disseminated multi-organ involvement (hepatitis)
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Toxoplasmosis
``` Toxoplasma gondii (parasiteº Cats, Faecal contamination Fever Pregnant women --> fetal abnormalities Immunocompromised --> CNS --> Seizures ```
330
Brucellosis
``` Gram -ve cocco-bacilli Cattle, Unpasteurised milk Fever, Sweats, Weight loss Back pain, Orchitis ```
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Coxiella burnetii (Q fever)
Goats, Unpasteurised milk/Aerolisation Atypical pneumonia NO RASH
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Rabies (LYSSA VIRUS)
``` Dogs, Cats, Bats Bites, Scratches, Infected fluid Fever Headache Salivation Agitation Negri bodies (pathognomonic) ```
333
Rat bite fever
``` Streptobacillus moniliformis (Gram -ve rod) Spirillum minus (Gram -ve rod) Fever Polyarthralgia Maculopapular rash ```
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Hantavirus pulmonary syndrome
Deer mouse - Sin Nombre virus Infected urine/droppings Acute respiratory distress syndrome
335
Viral haemorrhagic fever
``` Includes - Ebola (bats) - Marburg (bats) - Lassa (rats) - CCHF (Ticks) Thrombocytopaenia --> bleeding Fever ```
336
sCJD - Ix
Brain biopsy
337
vCJD - Ix
MRI: Pulvinar sign | Tonsillar biopsy - only done for vCJG (NOT for sCJD)
338
CJD - Tx
Symptomatic only - Clonazepam - for myoclonus - Quinacrine (anti-malarial) - delay prion conversion - Pentosan - Tetracycline - Anti-prion Ab
339
vCJD vs sCJD
vCJD has younger age of onset + Psychiatry symptoms first (before neuro Sx)
340
Sx of CJD
``` Rapid progress dementia Myoclonus Cortical blindness Akinetic mutism LMN signs ```
341
Sx of Kuru
Progressive cerebellar syndrome
342
Sx of GSS
Dysarthria --> Cerebellar ataxia --> Dementia
343
Sx of FFI
Insomnia --> Hallucinations
344
Epidermodysplasia verruciformis
EVER1/2 mutation --> ↑ risk of HPV infection
345
AIDS defining conditions
``` Oesophageal candidiasis Cervical cancer (invasive) CMV retinitis Kaposi sarcoma (HHV8) Burkitt's lymhoma PCP PML (JC virus) ```
346
HIGH to LOW risk of opportunistic viral infections
``` Allogenic stem cell transplant Advanced HIV Solid organ transplant monoclonal antibody therapy Cytotoxic chemotherapy Steroids ```
347
Progressive multifocal leukoencephalopathy
JC virus Demyelination of white matter tracts Focal neurological signs Cognitive disturbance
348
BK virus - Sx
Post-stem cell transplant --> BK cystitis Post-renal transplant --> BK nephropathy Tx: Cidofovir
349
Types of helminths
``` Cestodes = tapeworms Trematodes = Flukes = no body cavity, gut Nematodes = Roundworms = earthworm-like, body tubes ends in anus ```
350
Pork tapeworm
Taenia solium - Eggs seen in faeces - Risk of cystericerosis (headache, seizures, confusion, major changes) - ------ Faecal-oral transmission, not from uncooked meat
351
Beef tapeworm
Taenia sagina | - Segments fall out of rectum
352
Poor and Beef tapeworm - Sx
Onset after 2-3 months D&V White rice grains in stools
353
Hyatid lifecycle
Normally Dog Sheep Humans eat dogshit contaminated food Tx: praziquantel +/- aspiration of cysts
354
Schistosomiasis types
``` S mansoni (Africa, S America) --> GI S haematoium (Africa) --> Bladder (haematuria) S mekongi S japonicum (China, Philippines) --> GI ```
355
Schistosomiasis life cycle
Contaminated freshwater Snails Release into water Infect through skin --> bladder or GI tract Ix: Stool/urine microscopy (look fro eggs), Biopsy (bladder, rectum) granulomatous lesions with eggs Tx: Praziquantel
356
Ascaris
Contaminated soil
357
Strongyloides
Contaminated mud --> foot --> lungs --> cough and swallowed --> SI --> eggs --> perianal skin Walking barefoot
358
Filariasis
``` Blackflies vector Lymphatics --> elephantiasis SC tissues Serous cavity USS: Dance sign ```
359
Myiasis
``` Bot fly OR Tumbu fly Non-healing skin lesion Itchiness Discharge from central punctum Fly larve lies in skin and bursts out and flies away NOT a worm ```
360
Most common cause of adult-onset seizures
Cystericerosis
361
Mechanism of cysticerosis
Contaminated pork eaten by Human 1 (asympatomatic, GI tapeworm, eggs excrete in faeces) Faecal-oral transmission to Human 2 --> CYSTICERCOSIS (eggs mature, invade tissue --> form cysts) Cysts may form in Brain, Muscles , Tongue
362
Gram +ve rod (branches) Alcoholics Lung abscess Microscopy: Basophilic granules, Grocott stain
Actinomyces
363
Leishmania
Cutaneous - Sandy fly bite, skin ulcer Diffuse cutaneous - nodular skin lesions Muco-cutaneous - dermal ulcer Visceral - Kala Azar, malnourished child, abdo discomfort, BM invasion, splenomegaly
364
Leptospirosis
Dog/Rat urine, Swimming, Fever, Jaundice, Meningism, Carditis, Haemolytic anaemia
365
Incubation period (1-6 hours)
S aureus, Bacillus cereus
366
Incubation period (12-48 hours)
Salmonella, Escherichia coli (watery)
367
Incubation period (48-72 hours)
Shigella (bloody), Campylobacter (flu prodrome)
368
Incubation period (7 days hours)
Amoebiasis (bloody), Giardiasis (non-bloody)