1
Q
Give some examples of penicillins.
A
Flucloxacillin
amoxillicin
benzylpenicillin
penicillin V
2
Q
Describe the mechanism of action of penicillins.
A
- attaches to penicillin-binding proteins on forming bacterial cell walls
- this inhibits transpeptidase enzyme which cross-links bacterial cell wall
- failure to cross-link induce cell autolysis
3
Q
When should flucloxacillin be used?
A
- soft tissue infection
- staphylococcal endocarditis
- otitis externa
4
Q
Which drug should be used in non-severe CAP?
A
amoxicillin
5
Q
List common side effects of penicillins.
A
- diarrhoea
- vomiting
- liver function impairment
- hypersensitivity reactions (anaphylaxis)
6
Q
Clavulonic acid is often given alongside which drug? And why?
A
amoxicillin, as it is beta-lactamase susceptible (mechanism of resistance) - forming co-amoxiclav
7
Q
Gentamicin is an example of which type of antibiotics?
A
aminoglycosides
8
Q
How does gentamicin work?
A
- binds to 30s ribosomal subunit, inhibiting protein synthesis, inducing a prolonged post-antibiotic bacteriostatic effect
- bactericidal action on cell wall results in rapid killing early in dosing interval and is prominent at high doses
- provides a synergistic effect when used alongside other antibiotics (e.g. flucloxacllin or vancomycin in gram+ve infections)
9
Q
When should gentamicin be used clinically?
A
- severe gram -ve infections e.g. biliary tract infection, pyelonephitis, HAP
- some severe gram +ve infections e.g. soft tissue infection, endocarditis
10
Q
Nephrotoxicity and ototoxicity are caused by high-dose prolonged exposure to which antibiotic?
A
Gentamicin
11
Q
Describe the importance of careful dosing in gentamicin prescribing.
A
- give high initial dose to take advantage of rapid killing
- leave long dosing interval to minimise toxicity
- measure trough level to ensure it is not accumulating
12
Q
How many days should you limit gentamicin use to?
A
3 days - minimise risk of SE
13
Q
Which antibiotics work by interfering with bacterial DNA replication and repair? Give an example of one.
A
Quinolones
e.g. ciprofloxacin
14
Q
Describe the spectrum of use and action of ciprofloxacin.
A
Broad spectrum bactericidal - both gram+ve and gram-ve cover
15
Q
List the indications of quinolone antibiotic use.
A
- gram-ve bacterial infection
- respiratory tract infection
- upper urinary tract infection
- peritoneal infection
- gonorrhoea
- prostatitis
16
Q
Give some side effects of ciprofloxacin.
A
- GI toxicity
- QT wave prolongation
- C. diff. infection (antibiotic associated diarrhoea)
- tendonitis (rare)
17
Q
Ceftriaxone and cephalexin are examples of which type of antibiotic?
A
Cephalosporin
18
Q
What is the mechanism of action of cephalosporins?
A
- attaches to penicillin-binding-proteins on forming bacterial cell walls
- this inhibits transpeptidase enzyme which cross-links bacterial cell wall
- failure to cross-link induces bacterial cell autolysis
19
Q
Are penicillins or cephalosporins more susceptible to beta-lactamases?
A
penicillins
20
Q
Describe the coverage of cephalosporins.
A
both gram+ve and gram-ve
21
Q
When should cephalosporins be used?
A
serious infection - septicaemia/pneumonia/meningitis
22
Q
What are the common side effects of cephalosporins?
A
- hypersensitivity reactions
- antibiotic-associated C. diff. diarrhoea
- liver function impairment
23
Q
How is cephalosporins excreted?
A
kidneys
24
Q
Cephalosporins have a long half-life, what impact does this have on their use?
A
needs to be given once daily
25
Which antibiotic group is bactericial, inhibiting cell-wall synthesis in gram+ve bacteria?
glycopeptides e.g. vancomycin
26
Which antibiotic is most commonly utilised in MRSA infection?
vancomycin
27
What are the clinical uses of vancomycin?
- severe gram+ve infections
- MRSA
- severe C. diff. infection
28
Vancomycin has many side effects. What are they?
- fever
- rash
- local phlebitis at site of injection
- nephrotoxicity
- ototoxicity
- blood disorders - neutropaenia
- anaphylactoid reaction if infusion rate too fast
29
How is vancomycin administered?
either given as a continuous IV infusion or as a pulsed infusion regimen
30
Why is therapeutic drug monitoring undertaken with vancomycin?
it has a narrow therapeutic range
31
Give two examples of macrolides.
clarithromycin
| erythromycin
32
Describe the mechanism of action of macrolides.
- bacteriostatic and bacteriocidal
- binds to 50s ribosomal subunit
- inhibits bacterial protein synthesis
33
When should macrolides be used?
- atypical organisms causing pneumonia/severe CAP
- severe campylobacter infection
- mild/moderate skin and soft tissue infection
- otitis media
- Lyme disease
- H. pylori eradication therapy
34
Which antibiotics use the hepatic enzyme cytP450 pathway? And so what drugs do they interact with?
macrolides - and so interact with all drugs using this pathway e.g. simvastatin, atorvastatin, warfarin
35
What important patient information needs to be given when administering macrolides?
- risk of diarrhoea
- senses of smell and taste may be disturbed
- tooth and tongue discolouration may occur
36
Describe the mechanism of action of trimethoprim.
- inhibits folate metabolism pathway and leads to impaired nucleotide synthesis
- therefore interferes with bacterial DNA replication
37
What are the indications of trimethoprim?
- first line antibiotic in uncomplicated UTI
- acute/chronic bronchitis
- pneumocystis pneumonia
- gram -ve, gram +ve and some MRSA cover
38
List the side effects of trimethoprim.
- elevated serum creatinine
- hyperkalaemia - especially in those with impaired renal function
- depressed haematopoiesis
- rash and GI disturbance
39
Note some important PK and PD of trimethoprim.
- penetrates well into the prostate - suitable for men with uncomplicated UTI
- avoid in first trimester of pregnancy
- resistant organisms
40
What are the 4C's that cause C. diff infection?
clindomycin, co-amoxiclav, cephalosporin, ciprofloxacin
41
Briefly describe the pathophysiology of C. diff infection.
- infection causes pseudomembranous colitis leading to severe diarrhoea, abdominal pain, fever and nausea
- toxins induce inflammation and cell death
42
List some anaerobes.
- clostridium
| - bacteroids
43
List some gram+ve coccus bacteria.
- staphylococcus
- streptococcus
- enterococcus
44
List some gram-ve rod bacteria.
- pseudomonas
- haemophilus
- E. coli
- other coliforms
45
List the 6 investigations that must be carried out within 1hr of sepsis recognition.
1. Perform blood cultures
2. Antibiotic administration
3. Oxygen to achieve target saturation
4. Measure lactate and Hb
5. IV fluids
6. Monitor urinary output hourly
46
IV amoxicillin should be administered in?
Group A strep infections
pneumococcus
meningococcus
47
List some gram+ve rod bacteria.
Clostridia
Bacillus
Listeria
48
Meningococcus is an example of what type of bacteria?
Gram-ve coccus
49
What is the SIRS criteria?
- Temperature: <36 °C or >38 °C
- Heart rate: >90/min
- Respiratory rate >20/min or PaCO2 <32 mmHg (4.3 kPa)
- WBC <4x10^9/L or >12x10^9/L
50
What is the standard short course therapy for tuberculosis?
Isoniazid & rifampicin for full 6 months
| Pyrazinamide & ethambutol for first 2 months
51
Which antibiotics are not safe to use during pregnancy? And why?
Tetracyclines: bone abnormalities
Trimethoprim: neural tube defects
Gentamicin: ototoxicity
Quinolone: bone abnormalities
52
Horizontal gene transfer has more importance in antimicrobial resistance. What are the three mechanisms of horizontal transfer?
Conjugation
Transduction
Transformation
53
Describe the four main mechanisms of antibiotic resistance.
1. Production of enzyme that inactive or modify antimicrobials eg beta lactamases
2. Target modification
3. Decreasing cell permeability
4. Bacteria export drug from inside cell, drug exchanges for protons
54
What does MRSA stand for?
Methicillin (flucloxicillin) resistant staphylococcus aureus
55
Which inherited condition is linked to a defect in the gene coding for NADPH oxidase? What is the consequence of this disease?
Chronic granulomatous disease
| Recurrent bacterial and fungal infections - abscesses, lung, lymph nodes, skin
56
Describe the pathophysiology of neutropenia in cancer patients.
Cytotoxic chemotherapy and therapeutic irradiation
Decreased proliferation of haemopoietic progenitor cells
Neutropenia
57
What is the clinical definition of neutropenia?
<0.5x10^9/L or <1.0x10^9/L and falling
58
What antibiotics should be prescribed in the immediate management of neutropenic shock?
Pipercillin & tazobactam
59
What pathogens commonly cause cellulitis?
Beta haemolytic strep group A
| S. Aureus
60
Which antibiotic should be prescribed initially in cellulitis?
Flucloxicillin
61
Describe the management plan for necrotising fasciitis.
Urgent surgical debridement
Clindomycin
Immunoglobulin
62
How would you manage a presentation of COPD exacerbation with green sputum?
Hospitalisation
Administer doxycycline or amoxicillin
<5 days
63
What are the clinical features of malaria?
fever, malaise, headache, myalgia, diarrhoea, anaemia, jaundice, renal impairment
64
How is malaria treated?
Riamet, quinine, doxycycline
65
What are the clinical features of dengue fever?
'breakbone fever' - headache, fever, retro-orbital pain, myalgia, rash, cough, sore throat, nausea, diarrhoea
66
What is seen in laboratory findings in dengue fever?
leucopenia, thrombocytopenia, transaminitis
67
How is dengue fever managed?
symptomatic
68
Describe the serious complication of dengue fever which is less likely to occur in travellers.
dengue haemorrhagic fever
| increased vascular permeability, thrombocytopenia, fever, bleeding
69
Which two pathogens cause enteric fever?
S. typhi
| S. paratyphi
70
Describe the clinical features of typhoid and paratyphoid.
GI: diarrhoea vs constipation, abdo pain, rectal bleeding, bowel perforation
neurological: headache, enteric encephalopathy
bacteraemia
71
How would a diagnosis of enteric fever be made?
travel history
blood culture
stool culture
72
How is enteric fever treated?
quinolones - effective but resistance an issue
cephalosporins - empirical therapy
azithromycin
73
List causes of viral haemorrhagic fever.
Lassa, Ebola/marburg, CCHF, SAVHFs, RVF, DHF, yellow fever
74
Discuss the natural history of viral haemorrhagic fever.
exposure - non-specific febrile illness - haemorrhagic manifestations - sepsis syndrome/shock - death
75
How is viral haemorrhagic fever managed?
supportive
correct coagulative/anaemia
ribavirin?
76
Define diarrhoea.
abnormal frequency and/or fluid stool - usually indicates small bowel disease and causes fluid and electrolyte loss
77
What is dysentery?
inflammatory disorder of large bowel leading to blood and pus in faeces, pain, fever and abdo cramps
78
What is haemolytic uraemic syndrome and which pathogen causes it?
E. coli 0157
microangiopathic haemolytic anaemia
thrombocytopenia
acute renal failure
79
Which pathogen causing gastroenteritis is associated with Guillain-Barre syndrome (ascending paralysis due to demyelination)?
campylobacter
80
Which pathogen is associated with causing cramps, vomiting and diarrhoea in reheated fried rice?
bacillus cereus
81
The clinical features associated with Clostridium botulinum infection differ from the usual symptoms of gastroenteritis such as diarrhoea and vomiting. What are they?
flaccid paralysis
progressive muscle weakness
resp. failure
82
What is the antibiotic treatment for Clostridium difficile?
moderate - metronidazole
| severe - oral vancomycin
83
What are the five viruses that cause gastroenteritis?
norovirus, rotavirus, sapovirus, adenovirus, astrovirus
84
How many genogroups does norovirus have? Which genotype is the most common?
5 - only 3 affect humans
| GII-4
85
Describe the clinical features of norovirus and how it is treated.
N&V, diarrhoea, abdo cramps, headache, myalgia, fever, dehydration
symptomatic therapy - fluids, antispasmodics, analgesics, antipyretics
86
What vaccine is available for rotavirus?
rotarix - protects against severe infection in first two years
87
Which antibodies and Igs are important in immunity against rotavirus?
VP7 and VP4
| secretory IgA
88
Which two strands of adenovirus commonly cause gastroenteritis?
40 and 41
89
What are the complications associated with rotavirus?
severe chronic diarrhoea, dehyrdation, electolyte imbalance, metabolic acidosis
90
How is the qSOFA score used to detect sepsis?
A score of ≥2 of:
- Confusion (<15 of Glasgow Coma Scale)
- Respiratory rate ≥22/minute
- Systolic blood pressure ≤100mmHg
91
A patient presents with a red, hot, swollen knee joint with pain and loss of movement. He also says that he has a fever. What are the initial investigations that you would carry out?
blood cultures, joint aspirate, FBC, CRP, imaging
92
What is osteomyelitis?
progressive infection of bone characterised by death of bone and the formation of sequestra
93
How might osteomyelitis be spread?
haematogenous
| contiguous - overlying infection e.g. cellulitic ulcer, trauma, surgery
94
Which bacteria commonly cause septic arthritis?
streptococcus
| MRSA/MSSA
95
Name an infection which causes spinal deformity and instability, cord compression, paraplegia and disability.
vertebral discitis - infection of a disc space and adjacent vertebrae
96
What are the risk factors associated with developing a prosthetic joint infection following primary arthroplasty?
RA, diabetes, poor nutritional status, obesity, concurrent UTI, steroids, malignancy
97
List some risk factors associated with developing a prosthetic joint infection following revision arthroplasty.
prior joint surgery, prolonged operating room time, pre-op infection
98
What two ways might a prosthetic joint infection spread?
local and haematogenous
99
Which antibiotics might be used as prophylatic therapy for PJI?
cephalosporins (+vanc if MRSA suspected)
100
What are the surgical options available in prosthetic joint infections?
1. DAIR - debride, antibiotics, implant retained, if <30 days
2. Take joint out > 30 days Girdlestone procedure
101
List some of the typical and atypical pathogens that cause pneumonia.
typical - strep. pneumoniae, haemophilus influenzae, moraxella catharralis
atypical - mycoplasma pneumoniae, legionella pneumoniae
102
What is the most common cause of community acquired pneumonia?
streptococcus pneumoniae
103
What the clinical features and examination findings associated with typical pneumonia?
CF: abrupt onset cough, fever, pleuritic chest pain
Examination: dull percussion, coarse crepitus, increased vocal resonance
104
Which strain of H. influenzae has been vaccinated against because it causes epiglottitis?
B
105
Which pathogens commonly cause pneumonia in patients with a bad underlying lung disease such as COPD or CF?
H. influenzae
| M. catharralis
106
What features of a clinical history would make you suspect a legionella pneumoniae infection?
near public waters, AC, warmer parts of world - aerosol of water or soil infects macrophages in lungs
107
Which pathogen is responsible for an atypical presentation of pneumonia which is initially flu-like with resp. symptoms developing over time?
legionella pneumoniae
108
Which investigation is crucial in diagnosing legionella pneumoniae infection?
urine antigen test
109
Which antibiotics are effective against atypical pneumonia infection?
ciprofloxacin
| clarithomycin
110
List the clinical features associated with the atypical mycoplasma pneumoniae.
non-specific flu-like, fever, cough
| outwith lungs = haemolysis, GB syndrome, erythema multiforme, cardiac, arthritis
111
Discuss the CURB65 clinical assessment score for diagnosing severe pneumonia.
```
C = confusion
U = urea > 7
R = RR > 30
B = BP dia < 60 and sys < 90
65 = over 65
> 2 + multilobular consolidation on CXR and/or hypoxia on room air = severe pneumonia
```
112
List the viral causes of the common cold and how it presents.
rhinovirus, coronavirus
| sore throat, rhinorrhoea, nasal obstruction, sinusitis, otitis media
113
What are the common viral causes of pharyngitis and how does its presentation differ from bacterial?
adenovirus, rhinovirus, influenza, parainfluenza, EBV
sore throat + pharyngeal inflammation = pharyngitis
+ nasal symptoms = viral
114
Croup presents in childhood with a very distinctive cough. What pathogen most commonly causes this?
parainfluenza virus 1-4
115
A child presents with a three week history of cough and week long history of wheeze and fast heart rate. Which pathogen is associated with this presentation?
respiratory syncytial virus - bronchiolitis
116
What medications are available to treat RSV infection? List some side effects associated with these.
1. Ribivirin
- tiredness, nausea, fever, pains
- severe: RBC breakdown, liver problems
2. Palivizumab
- prophylactic monoclonal antibody
- given IM monthly - expensive
117
Influenza presents with a 3-5 day history of flu-like and respiratory symptoms. What complications are associated with this virus?
- common: otitis media, sinusitis, pneumonia, dehydration, exacerbation of underlying disease
- uncommon: encephalopathy, Reye syndrome, myositis, myocarditis
118
What groups are more susceptible to severe influenza infection?
>65s, <6m, pregnancy, obesity, diabetes, immunosuppression, organ damage
119
Which virulence factor produced by Staphylococcus aureus is associated with severe rapidly progressing necrotising infection?
Panton-Valentine leucocidin
120
A 27 year old man with HIV has a raised red lesion on his back and a clinical diagnosis of Kaposi's sarcoma is made. Which virus is associated with Kaposi's sarcoma?
human herpes virus 8
121
What are the symptoms of TB?
cough, fever, night sweats, SOB, weight loss, haemoptysis, pleural effusion
122
Describe the progression of infection of TB.
1. TB is inhaled - mycobacterium tuberculosis
2. TB meets macrophages and secretes a substance that prevents the lysosome from fusing with the phagosome so TB remains within macrophages
3. Haematogenous spread
4. Reactivation of TB - after immunosuppression, HIV infection or smoking leads to cavitary TB
5. Cavities open into bronchi, allowing spread by coughing
123
Discuss the lab tests used to detect TB.
T spot test
tuberculin skin test - Mantoux reaction for latent TB
Zeihl Neelson stain - purple rods specific for TB
AAFB positive lab test
124
Granuloma is a pathological hallmark of TB. Can you describe its appearance?
central caseous necrosis surrounded by epithelial cells, Langhan's giant cells and lymphocytes
125
What are the side effects associated with the drugs prescribed in TB?
rifampicin = reddish urine
isoniazid = liver toxicity
pyrazanimade
ethambutol = vision
126
A young woman presents with history of burning on urination and vaginal discharge. You require a urine culture and there appears to be a gram -ve diplococci bacteria present. What is the diagnosis?
gonorrhoea
127
Where should a swab be taken to carry out a NAAT test for gonorrhoea and chlamydia?
- male: urine sample +/- throat swab (MSM)
| - female: vulvovaginal swab
128
What are the symptoms of disseminated gonorrhoea?
skin pustules, septic arthritis, meningitis, endocarditis
129
Discuss the antibiotic treatment of gonorrhoea.
ceftriaxone and azithromycin
130
What is a major complication of chlamydia in females?
tubal damage/infertility
131
What antibiotics should be used following diagnosis of chlamydia?
doxycyline and azithromycin
132
What is lymphogranuloma venereum associated with chlamydia?
lymphotrophic chlamydia
severe proctitis causing constipation and rectal bleeding
inguinal 'bubos'
133
What pathogen causes syphilus?
Treponema pallidum bacteria
134
Describe the natural progression of syphilus.
- 3 weeks: first lesion = chancre = firm, painless, non-itchy skin ulcer
- 8-16 weeks: second lesion = rash = symmetrical, reddish, non-itchy on trunk
- latent syphilus (+ve serology only)
- 10-40 years: tertiary syphilus: gumma, CV, neurological
135
What are some of the most generalised symptoms of syphilus?
fever, malaise, hair loss, weight loss, headache
136
Describe the treatment for syphilus.
single IM benzathic benzylpenicillin
137
Name three viral STIs.
genital warts
molluscum contagiosum
herpes simplex
138
What vaccination is available for genital warts?
Gardasil - HPV 6, 11, 16, 18
139
What treatment is available for genital warts?
physically ablative
| topical agents
140
Pox virus causes which viral STI and causes raised, pearl-like papules or nodules in pubic area/groin?
molluscum contagiosum
141
Describe the classical presentation of herpes simplex.
clusters of inflamed papules and vesicles on outer surface of genitals resembling cold sores
142
What is the name of the drug used in the treatment of herpes simplex virus?
aciclovir
143
What is the mechanism of action of aciclovir?
A guanosine derivative, converted to triphosphate by infected host cells. Aciclovir triphosphate then inhibits DNA polymerase, terminating the nucleotide chain and inhibiting viral DNA replication.
144
What is the mechanism by which HIV causes illness?
- infects cells of the immune systems which carry CD4 receptors to allow HIV entry
- causes depletion of CD4 T helper cells by direct viral killing of cells, apoptosis of uninfected 'bystander cells,' CD8+ cytotoxic T cell killing of infected CD4+ cells
- abnormal B cell activation resulting in excess/inappropriate Ig production
- CD4+ cells fall below 200 - risk of opportunistic infections and cancers
145
Describe the mechanisms by which the drugs available for HIV work.
- fusion inhibitor/R5 inhibitor
- NRTI/NNRTI
- integrase inhibitor
- protease inhibitor
146
What is HIV latency?
a state of reversibly non-productive infection of individual cells
long symptomatic period between initial infection and AIDS
147
What are the two main clinical markers of HIV?
1. CD4 cell count: risk of opportunistic infection increases sharply below 200/mm^3
2. HIV-1 plasma RNA using ELISA: viral load test, below 10^4 low, above 10^5/ml high
148
Describe the presentation of acute HIV infection.
```
fever, malaise, headache, weight, N&V
liver and spleen enlargement
lymphadenopathy
pharyngitis and oral sores/thrush
maculopapular rash
```
149
What are the differential diagnoses of acute HIV infection?
- infectious mononucleosis: rash, pharyngitis, lymphadenopathy
- secondary syphilus
- drug rash
- viral infections: CMV, rubella, influenza, parvovirus
150
What does HAART stand for, what is it and what is its aim?
- highly active anti-retroviral treatment
- 'triple therapy': 2 nucleosides + 1 drug from another class
- aim: suppress viral load to undetectable and CD4 recovery
151
List some of the short and long term toxicities associated with HAART treatment of HIV.
- short: rash, hypersensitivity, CNS, GI, renal, hepatic
| - long: lipodystrophy, renal, hepatic, lipid, bone
152
What are the drug interactions associated with HAART?
mediated by CYP450 - PPIs, statins, antipsychotics
153
Describe three microbiological characteristics of C. difficile.
anaerobic, gram+ve bacilli, spore forming, toxin producing, antibiotic resistant, part of normal bowel flora
154
What parameters would you use to assess and classify the severity of CDAD?
- colonic dilatation > 6cm
- WCC > 15
- creatinine > 1.5X baseline
- temp > 38.5
- immunosuppression
155
What are the GI complications of CDAD
pseudomembranous colitis, toxic megacolon, perforation
156
Which organisms commonly associated with CAP are normally resistant to beta-lactam therapy?
mycoplasma, legionella, chlamydia
Phase 3
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