Microbio Flashcards
Inherently resistant antibiotics
bacteria lack a pathway or target which a drug interacts with, or the drug is unable to gain access to the target.
Acquired antibiotic resistance
where a bacteria which was previously sensitive has gained some genetic material encoding for resistance.
What are the 4 mechanisms of antibiotic resistance?
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)
How do bacteria acquire genes mediating resistance?
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.
What is the difference between horizontal and vertical gene transfer?
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.
Plasmids
pieces of circular double stranded DNA
Can either exist free within the cell or become integrated into the host chromosome
Fitness cost and selection pressure
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.
How do beta lactams work?
hydrolyse the beta lactam ring
What are Extended Spectrum Beta-Lactamases?
enzymes which are able to hydrolyse the beta-lactam ring of penicillins and cephalosporins
Treat with meropenem (carbapenem)
Which enzymes are able to hydrolyse meropenem?
carbapenemases
Pseudomonas aeruginosa antimicrobial resistance
multiple modifying enzymes
porin down regulation
4 efflux pumps
generally more resistant to antibiotics than other Gram negatives
Name 3 Non-genetic mechanisms of resistance
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
How does biofilm lead to resistance?
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.
biofilm
highly organised and complex bacterial community with channels for diffusion of water, oxygen and nutrients.
can form on the surface of prostheses and catheters
Debridement
removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue
Ways to prevent spread of resistance
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
What are the 3 main kinds of conditions seen in returning travellers?
GI disease
Nonspecific febrile illness
Skin manifestations, including sun damage
What are some causative organisms of travellers diarrhoea?
- Enterotoxigenic E.coli
- Enteroaggregative E.coli
- Campylobacter
- Salmonella
- Norovirus – one of the most common causes of travelers diarrhea
- Rotavirus – in children
most common causes of undifferentiated fever (systemic febrile illness) by region
- Subsaharan Africa - Malaria
- SE Asia - Dengue fever
- Central Asia – typhoid
- Caribbean – dengue fever
- Americas – dengue/malaria
Which illnesses are transmitted by the Aedes (tiger mosquito)
chikungunya, yellow fever, dengue fever
Malaria: plasmodium life cycle
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
Malaria diagnosis
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
Clinical features of malaria
o Fever
o Headache
o myalgia
- Anaemia
- Jaundice
- Renal impairment – particularly in falciparum malaria
How is severe malaria defined?
o Parasitaemia >2%
Malaria treatment
Riamet (fewer side effects)
Quinine and Doxycycline
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
Enteric Fever
o Salmonella typhi
o Salmonella paratyphi
(typhoid and paratyphoid)
Typhoid transmission
- Human reservoir only (no animal reservoir)
- Human to human
- Faecally-contaminated food/water
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
symptoms of typhoid
Fever Headache myalgia cough abdominal pain constipation diarrhoea
can resent with neurological manifestations
Treatment of typhoid
Quinolones
o Most effective agents
Cephalosporins
o Empiric therapy
o Longer courses required (14 days)
Azithromycin
o Oral option for treatment
What is the most common mosquito-borne virus in the world?
dengue fever
Spread by the aedes mosquito
Day biting
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
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
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
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
What is Safety netting?
“if symptoms get worse come and see me”
What is IVOST?
Adult IV to Oral Antibiotic Switch Therapy
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)
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
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
Sepsis
likely or confirmed infection + organ dysfunction
Life-threatening organ dysfunction which occurs as a result of a dysregulated host response to an infection
Sequential Organ Failure Assessment (SOFA) score
Predicts ICU mortality in septic patients
Used to quantify the extent of organ failure
score of ≥ 2 = sepsis
“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%
SIRS
HR > 90
Temp >38 or <36
Respiratory rate >20
WCC >12 or <4
Remember: tachy tachy whitey tempy
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
Neutropaenia definition
WCC <0.5 x 10^9/L or <1.0 x 10^9/L & falling
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
Name 4 Gram positive cocci
Staph aureus
coagulase negative staph
enterococci
strep viridans
Name 2 anaerobes
Bacteriodes
Clostridia
Name 4 Gram negative bacilli
E. coli
Pseudomonas aeruginosa
Klebsiella pneumoniae
Enterobacter
Name 2 fungal species
Candida
Aspergillus
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)
Give 5 causes of suppressed cellular immunity
DiGeorge syndrome cytotoxic chemotherapy irradiation lymphoma immunosuppressive therapy
Give 3 causes of reduced humoral immunity
Bruton agammaglobulinaemia
lymphoproliferative disorders
radiotherapy/chemotherapy
hypogammaglobulinaemia
state of deficiency of plasma gamma globulins and impairment of antibody formation
Severe nutritional deficiency
<75% ideal body weight or
Rapid weight loss + Hypoalbuminaemia
Pneumocystis jirovecii
“PCP”
fungus
causes severe lung infections
common in transplant recipients
most common opportunistic infection in persons with HIV infection
Aspergillus
fungus
commonly affects patients who have had chemotherapy or febrile neutropaenia
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.
VZV complication in the immunocompromised
shingles
can cause pneumonitis (inflammation of the walls of the alveoli)
Most common pathogens in neutropaenic cancer patients
gram positive bacteria
e.g. staph aureus, listeria
FEVER definition
Pyrexia OR Hypothermia
temperature > 38C or < 36C
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
SEPSIS
EVIDENCE OF INFECTION (including SIRS) + ORGAN DYSFUNCTION
i.e. ≥ 1 of:
hypotension
confusion
tachypnoea (Resp Rate ≥22/minute)
SEPTIC SHOCK
septic shock = sepsis + hypotension despite fluid resuscitation
Which groups are at the highest risk of viral gastroenteritis?
Children under age 5
Elderly - especially in nursing home
Immunocompromised
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
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
symptoms of norovirus
Vomiting Diarrhoea Nausea Abdominal cramps Viral symptoms - Headache, muscle aches
Dehydration common in young and elderly
Norovirus immunity
antibodies are developed to norovirus, but immunity only lasts 6-14 weeks.
some people are more susceptible to norovirus than others
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
Norovirus structure
Non enveloped, single stranded RNA virus
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
Rotarix®
rotavirus vaccine
live attenuated vaccine
Oral vaccine
