Microbio Flashcards
1
Q
Inherently resistant antibiotics
A
bacteria lack a pathway or target which a drug interacts with, or the drug is unable to gain access to the target.
2
Q
Acquired antibiotic resistance
A
where a bacteria which was previously sensitive has gained some genetic material encoding for resistance.
3
Q
What are the 4 mechanisms of antibiotic resistance?
A
1) Inactivating enzymes that cause alteration/degradation of antibiotic
2) Mutation of target site where antibiotic normally binds
3) Decreasing the permeability of the cell to the drug, meaning that the concentration required for the drug to be effective is not achieved
4) Export the drug from inside the cell (efflux pumps)
4
Q
How do bacteria acquire genes mediating resistance?
A
1) chromosomal mutations can arise
2) Conjugation - acquisition of a mobile piece of DNA . i.e. Receiving a plasmid bearing a resistance gene from another bacterium directly. (requires cell-cell contact)
3) DNA uptake from the environment through transformation
4) Receiving a resistance gene from another bacterium by viral transfection.
5
Q
What is the difference between horizontal and vertical gene transfer?
A
VERTICAL
genetic information is transferred from parent cell to progeny via binary fission.
HORIZONTAL
genes are transferred other than through traditional reproduction (can be between different species!)
primary reason for antibiotic resistance.
6
Q
Plasmids
A
pieces of circular double stranded DNA
Can either exist free within the cell or become integrated into the host chromosome
7
Q
Fitness cost and selection pressure
A
Because antibiotics attack important biological functions in a cell, mutations to avoid these antibiotics may also result in changes to the normal functioning of the bacterial cell.
These mutations may result in a reduced growth rate - known as a fitness cost
In an environment without a selective pressure, these slower growing mutants will be outgrown by the wild type bacteria and will slowly die away.
8
Q
How do beta lactams work?
A
hydrolyse the beta lactam ring
9
Q
What are Extended Spectrum Beta-Lactamases?
A
enzymes which are able to hydrolyse the beta-lactam ring of penicillins and cephalosporins
Treat with meropenem (carbapenem)
10
Q
Which enzymes are able to hydrolyse meropenem?
A
carbapenemases
11
Q
Pseudomonas aeruginosa antimicrobial resistance
A
multiple modifying enzymes
porin down regulation
4 efflux pumps
generally more resistant to antibiotics than other Gram negatives
12
Q
Name 3 Non-genetic mechanisms of resistance
A
1) Protected environment (e.g. abscess. May require lancing)
2) Resting stage - Bacteria which are not dividing are less susceptible to cell wall inhibiting agents e.g. TB
3) Presence of a foreign body - immune system is not as effective in the presence of a foreign body + BIOFILM
13
Q
How does biofilm lead to resistance?
A
The close proximity of bacteria to each other facilitates gene exchange
The channels for diffusion of nutrients are sometimes too small for antibiotics to penetrate well.
At the bottom of the biofilm, nutrients penetrate in smaller amounts, so the bacteria replicate slower making them less susceptible to cell wall agents.
14
Q
biofilm
A
highly organised and complex bacterial community with channels for diffusion of water, oxygen and nutrients.
can form on the surface of prostheses and catheters
15
Q
Debridement
A
removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue
16
Q
Ways to prevent spread of resistance
A
use narrow spectrum drugs where possible
Follow the empirical prescribing guidance
Using short courses of antibiotics where possible
Only use meropenem when absolutely necessary
Limit non-medical uses of antibiotics
infection control measures
17
Q
What are the 3 main kinds of conditions seen in returning travellers?
A
GI disease
Nonspecific febrile illness
Skin manifestations, including sun damage
18
Q
What are some causative organisms of travellers diarrhoea?
A
- Enterotoxigenic E.coli
- Enteroaggregative E.coli
- Campylobacter
- Salmonella
- Norovirus – one of the most common causes of travelers diarrhea
- Rotavirus – in children
19
Q
most common causes of undifferentiated fever (systemic febrile illness) by region
A
- Subsaharan Africa - Malaria
- SE Asia - Dengue fever
- Central Asia – typhoid
- Caribbean – dengue fever
- Americas – dengue/malaria
20
Q
Which illnesses are transmitted by the Aedes (tiger mosquito)
A
chikungunya, yellow fever, dengue fever
21
Q
Malaria: plasmodium life cycle
A
involves two hosts:
During a blood meal, a malaria-infected female Anopheles mosquito inoculates her saliva (containing sporozoites) under the skin
Sporozoites progress through the blood to the liver . infect liver cells and mature into schizonts
shizonts rupture and release merozoites, which infect red blood cells .
undergo asexual multiplication in the erythrocytes and cause cell lysis
o this is when you get symptoms
o Blood stage parasites are responsible for the clinical manifestations of the disease
22
Q
Malaria diagnosis
A
Antigen testing (rapid diagnostic test)
Blood films:
o thick films
o thin films – can be used to determine whether the patient has falciparum/nonfalciparum malaria
PCR – can be used to determine whether the patient has falciparum/nonfalciparum malaria
o Not widely used outside of research centres
NB: you need 3 negative antigen tests to rule out malaria
23
Q
Clinical features of malaria
A
o Fever
o Headache
o myalgia
- Anaemia
- Jaundice
- Renal impairment – particularly in falciparum malaria
24
Q
How is severe malaria defined?
A
o Parasitaemia >2%
25
Malaria treatment
Riamet (fewer side effects)
Quinine and Doxycycline
26
Malaria Chemoprophylaxis
Mefloquine (Larium)
o Once weekly but psychiatric side effects
Doxycycline
o Antibiotic
o Daily
o Photosensitisation
Malarone
o Atovaquone/proguanil
o Minimal side effects
o Cost
27
Enteric Fever
o Salmonella typhi
o Salmonella paratyphi
(typhoid and paratyphoid)
28
Typhoid transmission
* Human reservoir only (no animal reservoir)
* Human to human
* Faecally-contaminated food/water
29
typhoid pathogenesis
* Consumption of contaminated water or food
* Organism is ingested
* Invades through peyers patches in small intestine
* Infects the reticuloendothelial system
* patient eventually become bacteraemic – this is when it becomes clinically symptomatic
NB: this is a blood infection, not a gut infection. It does not necessarily cause diarrhoea
30
symptoms of typhoid
```
Fever
Headache
myalgia
cough
abdominal pain
constipation
diarrhoea
```
can resent with neurological manifestations
31
Treatment of typhoid
Quinolones
o Most effective agents
Cephalosporins
o Empiric therapy
o Longer courses required (14 days)
Azithromycin
o Oral option for treatment
32
What is the most common mosquito-borne virus in the world?
dengue fever
Spread by the aedes mosquito
Day biting
33
symptoms of dengue fever
“Breakbone Fever”
o Headache
o Fever
o Arthralgia/myalgia
```
o Rash – faint macular rash resembling sunburn
o Cough
o Sore throat
o Nausea
o Diarrhoea
```
34
Clinical presentation of haemorrhagic fever
Initially non-specific febrile illness:
o Fever
o Myalgia
o Headache
then become profoundly thrombocytopaenic and start bleeding from mucous membranes
o Haemoptysis
o PR bleeding
o Bleeding from venflon sites
• Septic shock results, this is what tends to kill people
35
What would you prescribe for a Severe/life-threatening infection?
Urgent blood cultures the antibiotics within one hour
Usually IV combination Rx (Beta lactam + Gentamicin) initially
e.g. amoxicillin + gentamicin
if penicillin allergic: vancomycin + gentamicin
if s. aureus suspected: amoxicillin + gentamicin + flucloxacillin
If streptococcal infection suspected: amoxicillin + gentamicin + clindamycin
36
What patient groups is staph aureus infection associated with?
healthcare-associated infections (e.g. nursing home residents or recent hospitalisation)
IVDU
wound infections/recent ost-op
37
What is Safety netting?
“if symptoms get worse come and see me”
38
What is IVOST?
Adult IV to Oral Antibiotic Switch Therapy
39
```
24 year old female
Previously well
Frequency and dysuria for 24 hours
Presents to GP
Urine dip stick +ve for leucocytes and nitrites
```
What is the diagnosis and what would you do?
Uncomplicated UTI
Recommend Fluids and analgesia (NSAID)
```
If antibiotics are prescribed - Trimethoprim or Nitrofurantoin in lower UTI
3 days (women)
7 days (men)
```
40
sepsis can be underrepresented as older patients. what are reasons for this?
may have a blunted inflammatory response
rather than having a high temperature, their fever may be masked by e.g. NSAID use
patient may be on a beta blocker - masks tachycardia
41
19 year old female
Sore throat, headache, neck pain
Rash
History of Penicillin allergy
BP 85/50
HR 124 bpm
RR 28
Temp 38.5
“Looks well”
What is the differential?
patient is septic
young people are able to appear well even when they are very unwell
meningitis
strep pyogenes infection - can often present without sore throat. neck pain is due to glands enlarging
Rash is a blanching erythrodema.
Patient has scarlet fever. She is developing streptococcal toxic shock
42
Sepsis
likely or confirmed infection + organ dysfunction
Life-threatening organ dysfunction which occurs as a result of a dysregulated host response to an infection
43
Sequential Organ Failure Assessment (SOFA) score
Predicts ICU mortality in septic patients
Used to quantify the extent of organ failure
score of ≥ 2 = sepsis
44
“Quick SOFA” score
= Confusion or Hypotension or Tachypnoea
Systolic BP < 100mmHg
Altered mental status
Respiratory rate > 22 breaths/min
⅔ quick sofa = mortality ~10%
3/3 quick sofa = mortality ~30%
45
SIRS
HR > 90
Temp >38 or <36
Respiratory rate >20
WCC >12 or <4
Remember: tachy tachy whitey tempy
46
Sepsis 6 (intervention tool)
All to be performed within 1 hour of sepsis recognition
BUFALO
```
Blood cultures
Urine output
Fluid resuscitation
Antibiotics IV
Lactate measurement
Oxygen to correct hypoxia
```
47
Neutropaenia definition
WCC <0.5 x 10^9/L or <1.0 x 10^9/L & falling
48
Name 2 causes of neutropaenia
cytotoxic chemotherapy
therapeutic irradiation
both cause reduced proliferation of HSC, which leads to depletion of marrow reserves, causing neutropaenia
can also affect neutrophil function
49
Name 4 Gram positive cocci
Staph aureus
coagulase negative staph
enterococci
strep viridans
50
Name 2 anaerobes
Bacteriodes
| Clostridia
51
Name 4 Gram negative bacilli
E. coli
Pseudomonas aeruginosa
Klebsiella pneumoniae
Enterobacter
52
Name 2 fungal species
Candida
| Aspergillus
53
Chronic Granulomatous Disease
Inherited defect in neutrophil function
Defect in gene coding for NADPH oxidase
- causes deficient production of oxygen radicals
- defective intracellular killing
Recurrent bacterial & fungal infections and widespread granulomatous inflammation (neutrophils are recruited to the site of infections but they are not effective, so more neutrophils are recruited)
54
Give 5 causes of suppressed cellular immunity
```
DiGeorge syndrome
cytotoxic chemotherapy
irradiation
lymphoma
immunosuppressive therapy
```
55
Give 3 causes of reduced humoral immunity
Bruton agammaglobulinaemia
lymphoproliferative disorders
radiotherapy/chemotherapy
56
hypogammaglobulinaemia
state of deficiency of plasma gamma globulins and impairment of antibody formation
57
Severe nutritional deficiency
<75% ideal body weight or
| Rapid weight loss + Hypoalbuminaemia
58
Pneumocystis jirovecii
“PCP”
fungus
causes severe lung infections
common in transplant recipients
most common opportunistic infection in persons with HIV infection
59
Aspergillus
fungus
| commonly affects patients who have had chemotherapy or febrile neutropaenia
60
HSV in patients who are immunocompromised
can be very out of control in patients who are immunocompromised
can affect many different parts of the body - skin, brain, lungs, etc.
61
VZV complication in the immunocompromised
shingles
| can cause pneumonitis (inflammation of the walls of the alveoli)
62
Most common pathogens in neutropaenic cancer patients
gram positive bacteria
e.g. staph aureus, listeria
63
FEVER definition
Pyrexia OR Hypothermia
| temperature > 38C or < 36C
64
SIRS (systemic inflammatory response syndrome)
inflammatory state affecting the whole body
2 or more of:
1) body temp <36 or >38
2) HR >90bpm
3) respiratory rate >20
4) white cell count <4x10^9 or >12x10^9
65
SEPSIS
EVIDENCE OF INFECTION (including SIRS) + ORGAN DYSFUNCTION
i.e. ≥ 1 of:
hypotension
confusion
tachypnoea (Resp Rate ≥22/minute)
66
SEPTIC SHOCK
septic shock = sepsis + hypotension despite fluid resuscitation
67
Which groups are at the highest risk of viral gastroenteritis?
Children under age 5
Elderly - especially in nursing home
Immunocompromised
68
Transmission of norovirus
faecal-oral
aerosolised e.g. by toilet flush
fomites - objects or materials which are likely to carry infection, such as clothes, utensils, and furniture.
NB: Contaminated hands are probably the single most common vector for the spread of Norovirus
69
Is norovirus enveloped or non-enveloped? What is the significance of this?
Non-enveloped. This makes it very stable
non-enveloped viruses can survive outside the body on surfaces etc.
may remain viable for long periods of time in the environment
70
symptoms of norovirus
```
Vomiting
Diarrhoea
Nausea
Abdominal cramps
Viral symptoms - Headache, muscle aches
```
Dehydration common in young and elderly
71
Norovirus immunity
antibodies are developed to norovirus, but immunity only lasts 6-14 weeks.
some people are more susceptible to norovirus than others
72
Rotavirus
Double stranded, non enveloped RNA virus
Mainly transmitted person to person via faeco-oral or fomites
generally doesn't affect healthy adults -> children, elderly and immunocompromised
73
Norovirus structure
Non enveloped, single stranded RNA virus
74
Symptoms of rotavirus:
Watery diarrhoea
Abdominal pain
Vomiting
Loss of electrolytes leading to dehydration
NB: 1st infection after age 3 months is usually the most severe, but doesn'd lead to permanent antibodies
this is because a breast fed baby is covered by the mum’s antibidoes for the first three months of life
75
Rotarix®
rotavirus vaccine
live attenuated vaccine
Oral vaccine
76
Adenovirus
Double stranded DNA virus
non-enveloped
Remember: aDenovirus is a DNA virus
77
Adenovirus symptoms
fever and watery diarrhoea
78
Astrovirus
Single stranded, non enveloped RNA virus
79
Detection of viral infections
detected by polymerase chain reaction (PCR)
this detects the DNA or RNA
Samples: vomit or stool
80
All of the following cause viral gastroenteritis except:
```
Rotavirus
Norovirus
Adenovirus 42 & 43
Astrovirus
Sapovirus
```
Adenovirus 42 & 43
Adenovirus 40 & 41 cause gastroenteritis
81
The most important consideration of the treatment of diarrhoea is:
```
– Antibiotics
– Antivirals
– Antispasmodics
– Salt and fluid replacement
– Vaccines
```
Salt and fluid replacement
82
The following are spread via the faeco oral route except:
```
Norovirus
Rotavirus
Poliovirus
Hepatitis D
Hepatitis E
```
Hepatitis D - co-infection with Hepatitis B, same forms of transmission
83
How are viral RTIs transmitted?
through the respiratory tract and conjunctiva
aerosol particles and indirect transmission via contaminated surfaces
84
Causes of the common cold
Rhinovirus
| Coronavirus
85
how can you differentiate between viral and bacterial pharyngitis?
Nasal symptoms = viral
| Without nasal symptoms = bacterial
86
what is the most common cause of viral pharyngitis?
Adenovirus
NB: pharyngitis is a common HIV seroconversion illness
87
what is the most common cause of croup?
parainfluenza viruses 1-4
88
Bronchiolitis
Lower respiratory tract infection of young children
Causes:
- Wheezing, tachycardia
- bronchiole narrowing makes it harder for the child to breathe. This causes tachycardia and exceptional fatigue → hospitalisation
89
what is the most common cause of Bronchiolitis?
RSV
90
Treatment of RSV
Ribivirin (broad spectrum antiviral agent)
91
Complications of influenza infection
Otitis media
sinusitis
dehydration (infants)
Causes 2 types of pneumonia:
primary viral influenza pneumonia - very rapid
very high mortality rate -> diffuse haemorrhagic pneumonia
bacterial pneumonia
patient has influenza and appears to recover.
4-14 days later, the patient develops fever, cough productive sputum and basal consolidation on CXR
92
Influenza Treatment
1) Neuraminidase Inhibitors
inhibit a protein found on the surface of the influenza virus that allows the progeny virus to leave the cell and infect other cells
2) M2 inhibitors
M2 is a protein present only in influenza A (enables viral uncoating). Inhibition prevent viral uncoating. Not effective against type B
93
What form of influenza is only found in humans?
Type B
94
What form of influenza demonstrates Antigenic shift?
Reassortment of gene segments involving 2 different influenza viruses → produces new virus subtypes
This occurs from the recombinant of different virus strains when they infect the same cell
Only occurs in influenza A, because it infects different animals
95
What is an influenza pandemic?
worldwide epidemics of a newly emerged strain of influenza
Occurs due to antigenic shift
Few, if any, people have any immunity to the new virus
This allows the new virus to spread widely, easily, and to cause more serious illness
96
Why does antigenic shift often occur in pigs?
bird flu and human flu have different preferred receptors, but both are found in pigs
therefore both a bird and human flu can infect a pig
when the two viruses are replicating in the pig, some segments from the segmented influenza genome will cross over and come together to form a new virus
97
What are the most common causative organisms of soft tissue and bone infections?
Gram positive organisms
- MSSA or MRSA
- Streptococci (S. pyogenes, Group G Strep, pneumococcus (commoner in children))
98
duration of treatment for bone infections
At least 2 weeks IV antibiotics.
often 3 weeks IV antibiotics followed by 3 weeks oral
99
Resection arthroplasty
taking the diseased joint out and putting in an artificial one
100
Arthrodesis
Fusing two bones together
101
Risk factors for joint infections
Primary Arthroplasty:
Rheumatoid arthritis - abnormal anatomy of joint
Diabetes mellitus - risk factor for all infections
Poor nutritional status
Obesity
Steroids
Revision Arthroplasty:
Prior joint surgery
Prolonged operating room time
Pre-op infection (teeth, skin, UTI)
102
3 most common causative organisms of prosthetic joint infections
1) staph aureus
2) CoNS (not seen in native joint infections)
3) streptococci
103
why does a prosthesis requires fewer bacteria to establish sepsis than soft tissue does?
1) Biofilm aspect
2) Avascular surface allows survival of bacteria as it protects from circulating immunological defences and most antibiotics
3) Cement can inhibit phagocytosis and lymphocyte/complement function - macrophages get clogged up with cement
104
surgical management of PJI: DAIR
DAIR to Leave the Infected Joint In
Debride, Antibiotics, Implant Retained
If prosthesis infection is acute (<30 days since insertion), then it is still mechanically functional and can be kept
infected tissues should be debrided and the joint washed out to reduce the burden of infection then IV antibiotics started for 4-6 weeks.
105
surgical options for management of PJI:
DAIR: Debride, Antibiotics, Implant Retained (<30 days)
Joint removal (>30 days) - take out prosthesis and all cement
106
Antibiotic therapy in PJI
use anti-biofilm agents:
- ciprofloxacin
- rifampicin
Abx need to penetrate bone
107
Osteomyelitis
Progressive infection of bone characterised by death of bone and the formation of sequestra
108
Vertebral discitis
Infection of a disc space and adjacent vertebral end plates.
Can be very destructive with deformity -> spinal instability risking cord compression, paraplegia and disability.
NB: Can be caused by TB
109
Most common cause of pneumonia
streptococcus pneumoniae
110
Typical causes of pneumonia
streptococcus pneumoniae
haemphilus influenza type b
moraxella
111
Atypical causes of pneumonia
mycoplasma pneumoniae
legionella pneumoniae
chlamydophila pneumoniae
112
risk factors for pneumonia
```
alcohol
smoking
airway disease
Influenza
Immunocompromise (especially HIV)
```
113
Typical presentation of pneumonia
symptoms:
- Abrupt Onset Cough
- Fever
- Pleuritic chest pain
Classic signs of consolidation on examination
- Dull percussion
- Coarse crepitations
- Increased vocal resonance
consolidation seen on CXR
114
treatment for Streptococcus pneumoniae/Haemophilus influenzae pneumonia
amoxicillin
If allergic:
Macrolides (clarithromycin)
Tetracyclines (doxycycline)
115
what is the most common atypical cause of pneumonia?
mycoplasma pneumoniae
116
mycoplasma pneumoniae pneumonia presentation
Often a non-specific presentation
flu-like symptoms
cough will not be the major symptom
```
Clinical features outwith the lungs:
Haemolysis
Guillain-Barre syndrome
Erythema multiforme - target lesions across the body
Reactive Arthritis
```
117
M. pneumoniae: treatment
Beta lactams tend to not be effective → No cell wall
Instead, use antibiotics with an intracellular mechanism:
Macrolides (clarithromycin)
Tetracyclines (doxycycline)
Quinolones (ciprofloxacin)
118
What would be the most common cause of pneumonia in a person exposed to a contaminated water system (hotel/jacuzzi)?
Legionella pneumophila
119
Legionella pneumonia presentation
headache
fever
malaise
120
Legionella diagnosis
most commonly diagnosed by a urine dipstick for urinary antigens
121
Legionella treatment
Beta lactams tend to not be effective → No cell wall
Instead, use antibiotics with an intracellular mechanism:
Macrolides (clarithromycin)
Tetracyclines (doxycycline)
Quinolones (ciprofloxacin)
122
Clinical assessment for severe pneumonia
CURB65 score
```
C - Confusion
U- Urea>7
R – Respiratory rate ≥ 30
B – BP hypotension, diastolic <60 or systolic <90
65 – Age over 65 years
```
score >2 = Severe pneumonia
Mortality increase with score 2 or more
123
which factors always indicate severe pneumonia (independent of CURB65 score)
Multilobar consolidation on CXR and/or Hypoxia on room air
ALWAYS = SEVERE PNEUMONIA
124
Mycobacterium tuberculosis
● obligate aerobe and intracellular pathogen
● usually infects mononuclear phagocytes.
● Forms very slow growing colonies
125
Risk Factors for TB
```
● Close contact (relative) with TB
● Immunocompromised e.g. HIV
● Drug/Alcohol abuse
● Homelessness
● overcrowded, poorly ventilated enclosed spaces
```
126
Stages of TB
* Primary infection (usually asymptomatic)
* Latent infection (dormant)
* Active infection
127
Ghon focus
Seen in TB
granulomatous tubercle that has undergone caseous necrosis
128
Ghon complex
ghon focus + lymph nodes
129
How does TB spread to non-pulmonary sites?
infected macrophages migrate to regional lymph nodes
where they access the bloodstream.
Organisms may then spread hematogenously to any part of the body
130
Secondary TB
Reactivation of primary infection or reinfection.
o Any organ initially seeded may become a site of reactivation, but occurs most often in the lung apices
Any form of immunocompromisation may allow reactivation.
131
Miliary TB
Aggressive form of TB that occurs throughout the whole lung.
Granuloma erodes into blood (bloodborne dissemination) or lymph vessels and the bacilli spread around the lungs
Predominantly seen in immunocompromised (HIV)
132
What is the most common extrapulmonary presentation of TB?
TB lymphadenopathy
Also:
- CNS TB
- Renal TB
133
TB symptoms
Cough - more productive (green/yellow sputum) as the disease progresses.
Low-grade fever
Drenching night sweats
Dyspnoea
Haemoptysis - only with cavitary TB
NB: With HIV coinfection, the clinical presentation is often atypical because DTH is impaired. Patients are more likely to have symptoms of extrapulmonary or disseminated disease.
134
Diagnosis of TB
• Sputum testing is the mainstay for diagnosis of pulmonary tuberculosis
* Chest x-ray
* Acid-fast stain and culture
* Tuberculin skin test (TST) or interferon-gamma release assay (IGRA)
135
Classical CXR findings in TB
multinodular infiltrate above or behind the clavicle
136
Mantoux Reaction
M. tuberculosis is injected just under the skin to create a local immune response.
positive in both latent and active infection and thus cannot distinguish between the two
A well-demarcated bleb or wheal should result immediately.
diameter measured 48 to 72 h after injection.
137
dutation of Drug Treatment of Tuberculosis
● Long duration – 6 months
| ● Combination of drugs to reduce rise of resistance
138
TB treatment regimen
● Rifampicin
● Isoniazid
● Pyrazinamide (stop after 2 months)
● Ethambutol (stop after 2 months)
NB: Give prophylactic pyridoxine to prevent neuropathy caused by isoniazid
139
Which bodily fluids can HIV can be transmitted from an infected person to another through? Which has the highest viral load?
* Blood (including menstrual blood)
* Semen
* Vaginal secretions
* Breast milk
Blood contains the highest concentration of the virus, followed by semen, followed by vaginal fluids, followed by breast milk.
140
Activities that Allow HIV Transmission
* Anal or vaginal intercourse
* Injecting drugs + sharing needles
* Mother-to-child transmission (before / during birth, or through breast milk)
* Transmission in health care settings
* Transmission via donated blood or blood clotting factors
141
How does HIV infection cause depletion of CD4 T helper cells?
* Direct viral killing of cells
* Apoptosis of uninfected “bystander cells”
* CD8+ cytotoxic T cell killing of infected CD4+cells
142
HIV structure
• Double stranded RNA
Has its own enzymes
• Reverse transcriptase
• Protease
• Integrase
143
HIV life cycle
1) Virus adheres to CD4 and then adheres to chemokine receptor.
2) Fusion and uncoating → release of RNA.
3) Reverse transcriptase (RT) in virion makes DNA.
4) DNA becomes integrated in the host DNA (integrase)
5) production of viral proteins to form a virion.
6) Virion buds from the cell.
144
viral latency (HIV)
long asymptomatic period between initial infection and advanced HIV
NB: virus continues to replicate
145
CD4 cell count
used as a marker of immune function
Important to know for HIV therapy
Marks when to start prophylaxis against opportunistic infections
Risk of opportunistic infection increases sharply below 200/mm3. Threshold for treatment = 350
146
HIV-1 plasma RNA
(Viral load test)
* Determines the level of HIV in the blood
* Marker for how well treatment is working
“Undetectable” = <40 copies/ml
147
Most common opportunistic infections seen with HIV
* PCP - pneumocystis jirovecii pneumonia
* CMV
* Candida
148
Natural history of HIV infection
Virus quickly replicates after infection – initial high viral load. Attacks immune system – resulting in depleted CD4 count
May have symptoms of acute seroconversion
Immune response mounts against the virus – viral load is reduced
• CD4 count recovers somewhat
• Clinically latent period ensues. may be asymptomatic for many years.
median time from initial infection to the development of AIDS among untreated patients is 8 to 10 years.
progressive loss of immune function. Constitutional symptoms occur as CD4 count dwindles
• Diarrhoea
• Oesophageal candida
depletion of the CD4+ T-lymphocytes leads to opportunistic infections and malignancies
149
symptoms of acute seroconversion
```
nonspecific and self-limiting:
– Fever
– Myalgia
– Headaches
– Maculopapular rash
```
150
Primary HIV Infection - Differential Diagnosis
* Infectious mononucleosis
* Secondary syphilis
* Drug rash
* Other viral infections – CMV, Rubella, Influenza, Parvovirus
151
HAART
Highly Active AntiRetroviral Treatment
• ‘triple therapy’ (cART = combined ART)
• 2 nucleosides
• 1 drug from another class
Tries to target the virus at different stages of its replication cycle
Aim to suppress viral load to undetectable
152
Challenges with ART
* Good adherence (>95%) essential
* Psychological impact
* Stigma
* Self-stigma
* Short term side-effects
* Drug-drug interactions
* Emerging longer term toxicities
153
Gonorrhoea
* caused by the bacteria Neisseria gonorrhoeae.
* Gram negative intracellular diplococci
Men typically develop purulent urethral discharge and dysuria
women may have a vaginal discharge.
Both men and women may be asymptomatic.
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diagnosis of gonorrhoea/chlamydia
* NAAT – nucleic acid amplification test
* PCR amplification of gonorrhoea DNA
* Combined chlamydia and gonorrhoea test
* Male heterosexual - Urine sample
* MSM – throat swab and rectal swab
* Female – vulvovaginal swab
• Confirm positive NAAT with GC culture (abx sensitivities)
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Disseminated gonorrhea
• Disseminated gonococcal infection
due to hematogenous spread
occurs predominantly in women.
affects the skin, tendon sheaths, and joints.
• Arthralgias, reactive arthritis
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Chlamydia trachomatis
Frequently asymptomatic
| Infection can lead to tubal damage / infertility
157
Lymphogranuloma venereum
* Strain of chlamydia
* Caused by serotypes of chlamydia that can invade and reproduce in regional lymph nodes
• characterized by a small, often asymptomatic skin lesion, followed by regional lymphadenopathy in the groin or pelvis.
Severe proctitis causing constipation, rectal bleeding
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Syphilis
caused by T. pallidum
Syphilis occurs in 3 stages:
• Primary - painless chancre (within 3 weeks)
• Secondary - maculopapular rash (8-16 weeks)
• Tertiary - neurosyphillis/cardiovascular (10-40y)
There are long latent periods between the stages.
Infected people are contagious during the first 2 stages
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Genital warts
* Caused by HPV type 6 and 11.
* Commonest STI seen in sexual health clinics.
Warts can be brought out by factors like:
o Smoking
o Immunosuppression
o Stress
• Risk increases as number of lifetime partners increases
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HPV Vaccination
* Gardasil – HPV strains 6/11/16/18
* School aged girls are vaccinated
* MSM attending sexual health/HIV clinics <45y
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Trichomonas Vaginalis (TV):
Trichomonas is a flagellated protozoan.
Up to 50% of men and women are asymptomatic
may produce a vaginal discharge and offensive odour in women and discharge or dysuria in men.
162
What tests are done during a sexual heath screen?
* Blood test for HIV + syphilis
* NAAT (nucleic acid amplification test) for gonorrhoea and Chlamydia.
• Hepatitis B in MSM and vaccination offered
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Which STI is associated with asymptomatic shedding?
Herpes simplex virus
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Proctitis
condition in which the lining tissue of the inner rectum becomes inflamed
165
Which common STIs co-infect?
patients with gonorrhoea will often have chlamydia as well (around 30%)
Therefore always treat for both gonorrhoea and chlamydia (doxycycline)
166
What can be done to minimize the development of drug resistant strains of gonorrhoea?
Rapid accurate diagnosis (microscopy, NAAT)
Avoidance of blind therapy with inappropriate drugs
Partner notification to limit the onward spread of resistant infection
Epidemiological monitoring
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A patient presents with a generalised maculopapular rash particularly affecting the hands and feet, alopecia, malaise and flu-like symptoms. What is the likely diagnosis?
secondary syphilis
Long incubation period - Primary syphilis can take up to 90 days and secondary syphilis up to 6 months to present
This is because treponemes are slow growing
Infection can only become apparent once the organism is present in sufficient numbers to disturb the host.
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what do 4th generation HIV tests look for?
HIV p24 antigen
will detect the great majority of individuals who have been infected with HIV at 4 weeks after specific exposure.
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Jarisch-Herxheimer reaction
a reaction to endotoxin-like products released by the death of harmful microorganisms within the body during antibiotic treatment
Cell wall fragments (antigenic fragments) in the blood stream generate an immune response
traditionally associated with antimicrobial treatment of syphilis.
170
important non-infectious causes of diarrhoea
inflammatory bowel disease (Crohn’s disease/Ulcerative colitis)
bowel cancer
diverticular disease
coeliac disease
HIV infection
171
most common cause of travellers diarrhoea
enterohaemmorhagic E.coli
172
When would you treat gastroenteritis with antibiotics?
when the patient has signs of sepsis (SIRS criteria)
if there is concern about CDI.
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Why should you avoid antibiotics in salmonella?
treating salmonella with antibiotics leads to long term carriage
quickly becomes resistant and establishes in the gallbladder
Do not treat with antibiotics unless absolutely necessary, e.g. severely immunocompromised patients or in invasive disease
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Which viruses cause a vesicular rash?
* Herpes simplex virus
* Varicella zoster virus
* Enteroviruses
175
How should blood cultures be taken when dealing with a patient with possible bacterial endocarditis (BE)?
```
3 sets within 24 hours
o Need to be an hour apart
• Need to come from separate sites
• Taken from peripheral veins
• Meticulous sterile technique
• Taken prior to antibiotics
• At least 10ml per sample
o The more blood you put in the sample the better
```
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Gram positive rods
C. diff
listeria
p. acnes
bacillus
177
Gram negative rods
```
pseudomonas
E. coli
Kleibsiella
Salmonella
Shigella
```
178
Name 3 common contaminants of blood cultures
Coagulase-negative staphylococci
Staphylococcus epidermidis
Staphylococcus aureus
179
Pathogenesis of Acute Cholecystitis
Gallbladder infections usually result from gallstone formation and impaction in the cystic duct,
Impaired biliary drainage leads to:
• infection
• oedema
• compression of local blood supply - may lead to gangrene of the gallbladder
Infection within the gallbladder may lead to:
• bloodstream infection
• cholangitis
• liver abscess formation
180
What antibiotics would you use to treat biliary sepsis?
Gentamicin + amoxicillin + metronidazole
covers: gram negative + gram positive + enteric flora
NB: therapy MUST include investigation to identify possible obstruction of the biliary tree -> decompression/drainage if required.
181
Main types of necrotising fasciitis
Type I - Synergistic infection with anaerobes and aerobes. Common in elderly/diabetics
Type II - Group A streptococci.
S. pyogenes or occasionally S.aureus
o mediated by toxin production.
182
Suggest an antibiotic regimen for necrotising fasciitis
```
o IV Flucloxacillin (for staphylococci)
o IV Benzylpenicillin (for streptococci)
o IV Gentamicin (for Gram negatives)
o IV Metronidazole (for anaerobes)
o Clindamycin (for anaerobes/toxin production).
```
IV antibiotics are important at this stage, but are unlikely to work whilst the necrotic tissue is present: this is avascular and full of organisms.
- requires urgent debridement
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Dermatophytes
fungi that cause common infections of skin, nails and hair
Do not colonise ‘live’ tissues
colonise keratinised areas such as nails and outer skin
have a very slow anaerobic metabolism
This means that response to treatment is slow, and they require prolonged treatment period
184
Name 3 Systemic fungal infections
1. Fungal meningitis
2. Aspergillosis of the lungs
3. Pneumocystis pneumonia
Only seen in immunocompromised patients
185
Mechanism of azole action
All act on the synthesis pathway for ergosterol
Ergosterol is an essential component of the fungal plasma membrane
If you inhibit it’s synthesis, you cure a fungal infection
Drawback: cross-resistance
186
Amphotericin B
Amphotericin B punctures fungal cells
Binds to ergosterol with its hydrophobic side
The hydrophilic side turns outward
Forms a channel through which water and ions can pass freely
This leads to cell death
187
How is Amphotericin B administered?
Cannot be given orally
Toxic on direct infusion into the veins, as it interacts with cholesterol at high concentrations
It is therefore packaged in liposomes (Ambisome)
188
What should you suspect with reduced level of consciousness in a febrile patient?
CNS infection
possible bacterial meningitis
