Week 6 - clinical microbiology Flashcards
What is the structural difference between a gram positive and gram negative bacteria?
Gram positive - thicker peptidoglycan cell wall
Gram negative- has an outer membrane and periplasm surrounding the cell wall.
How does a gram positive and gram negative strain appear differently after gram staining? What stain is used?
Gram positive - dark purple
Gram negative - paler
Crystal violet
Describe bactericidal and bacteriostatic antibiotics. What is a potential negative aspect of each?
Bactericidal - sterilise infected site by directly killing bacteria. Lysis of bacteria can lead to release of toxins and inflammatory material.
Bacteriostatic - suppresses growth but does not directly sterilise infected site. Requires additional factors to kill bacteria i.e. immune response.
What is meant by the term ‘antibiotic spectrum’?
The range of bacterial species that is effectively treated by the antibiotic.
What is the effect of broad and narrow spectrum antibiotics on colonising bacteria?
Broad - large effect on colonising bacteria.
Narrow - limited effect on colonising bacteria.
Define the following terms:
- Guided therapy
- empirical therapy
- prophylactic therapy
Guided therapy - identifying cause of infection and basing therapy on sensitivity testing.
Empirical therapy - educated guess based on clinical and epidemiological evidence when therapy cannot wait for culture.
Prophylactic therapy - preventing infection before it begins.
What is the mechanism of action of β-lactam antibiotics?
Inhibit cross-linking of cell wall peptidoglycan. Causes lysis of bacteria (bactericidal).
Name 5 β-lactam antibiotics and which class they belong to.
Penicillins - benzylpenicillin, amoxicillin, flucloxacilin.
Cephalosporins - ceftriaxone.
Carbapenems - meropenem
Monobactams - aztreonam.
What are beta-lactamases? What bacteria are they commonly secreted by?
Enzymes that lyse and inactivate beta-lactam drugs. Gram negatives and S. aureas.
How is TB treated?
6 month treatment period. 6 month course of Isoniazid and rifampicin + pyrazinamide and ethambutol for the first 2 months of the 6 month treatment.
What antibiotic classes are thought to be safe in pregnancy?
Most beta-lactams
Macrolides
Anti-tuberculants
Describe what is meant by ‘inherent resistance’ and ‘acquired resistance’.
‘Inherent resistance’ - there is no pathway or target for the drug/the drug cannot reach the target.
‘acquired resistance’ - a drug was previously sensitive but has gained some genetic material coding for resistance.
What are the 4 mechanisms of drug resistance?
1 - bacteria can produce enzymes with inactivate antibiotics i.e. beta-lactamases.
2 - bacteria can change the drug target by a mutation.
3 - decreased permeability of the cell to the drug.
4 - exporting of the drug out of cells in exchange for protons.
What are 4 ways that bacteria can acquire resistance?
- Chromosal mutation
- Acquisition of mobile DNA such as plasmids.
- Transformation
- Transduction - transfer of DNA between bacteria and viruses.
What is the difference between vertical and horizontal gene transfer? Which is more important in antibiotic resistance?
Vertical - genetic information passed from parent cell to progeny.
Horizontal - genes transferred other than through traditional reproduction.
Horizontal is the most important.
What is the rate of spontaneous resistance mutations? How does the spontaneous mutation rate compare to the rate of acquisition of mobile pieces of DNA?
Resistance mutations occur every 10^-8 - 10^-9 bacteria exposed to a drug.
Spontaneous mutation rate lower.
What is conjugation?
The transfer of plasmids between two bacteria. Most important mechanism of horizontal gene transfer.
What is transduction?
Where small pieces of DNA are transferred between bacteria by a virus (bacteriophage).
What is transformation?
As bacteria die some naked DNA is released into the surrounding environment and some bacteria are capable of taking up this DNA and inserting it into their chromosome.
Explain the need for a balance between fitness cost and selective pressure for a mutation to be successful in producing drug resistance.
Mutations may reduce bacterial growth which is called a fitness cost.
In an environment without a selective pressure these slower growing mutants will be outgrown by their wildtype colleagues and will die away.
What are 4 ways of preventing spread of resistance?
1 - narrow spectrum antibiotics where possible
2 - follow empirical prescribing guidlines
3 - short courses
4 - use of infection control measures especially when in contact with patients colonised with resistant bacteria.
What are the causes of primary and secondary immunodeficiency? Which is more common?
Primary - inherited, exposure in utero to environmental factors.
Secondary - underlying disease state, treatment for disease.
Secondary is more common.
The population of immunocompromised patients is increasing. Give 4 reasons for this.
- better cancer treatments
- developments in transplant techniques
- improved survival at extremes of life
- steroids
Neutropaenia is a state of low levels of neutrophils and is the most important risk factor for infection. What causes it?
Cytotoxic chemotherapy or therapeutic irradiation leads to reduced proliferation of haemopoetic progenitor cells and depletion of marrow reserves.
What is the definition of neutropenia in terms of number of neutrophils per litre.
- 5 x 10^9/L or
1. 0 x 10^9/L and falling
What five things are monitored in the antibiotic stewardship programme?
- volume of antibiotic prescribing
- quality of antibiotic prescribing
- antimicrobial resistance
- C. Difficile
- Other adverse events related to antibiotics
What questions should be asked when considering prescribing antibiotics?
Is an antibiotic required? Which antibiotic? How should it be administered? Adjunctive measures? How long?
What 5 times do you need to perform hand washing?
Before touching a patient Before a procedure After a procedure or body fluid exposure risk After touching a patient After touching patient surroundings
List 4 strategies for preventing healthcare associated infection (HAI).
- isolation
- screening
- cohorting
- Antimicrobial stewardship
When trying to manage a febrile returning traveller, history is crucial! What questions should you include?
Pre-morbid conditions? Pre-travel vaccinations? What country? Urban or rural? How long were they away? How long back in the UK? How did they travel? What did they do i.e. lake swimming? Sexual history?
Describe some of the methods of avoiding mosquito bites when travelling?
Staying indoors if there is AC and screens.
Impregnated netting.
Covering up with clothing.
Using DEET mosquito spray.
What are some of the clinical features of malaria?
Fever, malaise, headache, myalgia, diarrhoea.
Anaemia
Jaundice
Renal impairment
What is the management of sepsis?
SEPSIS 6
Administer oxygen therapy, IV access and commence IV fluids, blood cultures, check blood tests: FBC and lactate, arrange to monitor urine output, administer antibiotics.
Define sepsis.
Sepsis is defined as the presence of likely or confirmed infection in addition to the presence of organ dysfunction suggesting an abnormal physiological response to the infection.
What is the inheritance pattern of chronic granulomatous disease? What enzyme is defective? What infections does it increase risk of?
X linked
NAPDH oxidase
Recurrent bacterial and fungal infections - abscesses on lung, lymph nodes, skin i.e. aspergillus, staph aureas.
What can reduce neutrophil numbers and function? What is the clinical definition of neutropenia?
Cytotoxic drugs i.e. chemotherapy, irradiation, steroids.
0.5x10^9/L or 1.0x10^9/L and falling.
What can suppress cellular immunity?
DiGeorge syndrome (a rare primary deficiency)
Malignant lymphoma
Cytotoxic chemotherapy
Extensive irradiation
Immunosuppressive drugs i.e. steroids, cyclosporin, rituximab
Allogeneic stem cell transplant esp. if GvH disease.
Infections i.e. HIV, measles, EBV.
What can cause deficiency in humoural immunity?
Bruton agammaglobulinaemia (primary, rare)
CLL, multiple myeloma
Intensive chemotherapy and radiotherapy
Splenectomy or hyposplenism
What infections is a host susceptible to if they have deficient humoural immunity?
Strep pneumoniae
Haemophilus influenzae type b
Neisseria meningitis
Name some common pathogens in neutropenic cancer patients.
Gram positive aerobic bacteria: coNS, staph. aureas
Gram negative aerobic: E coli, klebsiella
Fungi: candida, pneumocystis, aspergillus
Viruses: HSV, VZV
Anaerobic: clostridium
What are some of the common aetiologies of travellers diarrhoea?
Bacteria - Enterotoxigenic E-coli, enteroaggregative E-coli, campylobacter, salmonella, shigella, C.diff
Viruses - norovirus, rotavirus, enterovirus
Parasitic - giardia, cryptosporidium
How would you manage travellers diarrhoea?
Fluid replacement
Antibiotics (quinolones and azithromycin) - wouldn’t normally give antibiotics for travellers diarrhoea as self limiting and increases resistance. Only if significant comorbidities.
CAUTION antimotility agents
Possible investigation for other causes - IBD, bowel cancer.
What are the two different types of mosquito? What time of the day do they bite and what diseases do they spread?
Aedes - spreads dengue fever, yellow fever - a day biter
Anopheline - spreads malaria - bit from dusk until dawn.
How do you physically avoid being bitten by mosquitos?
Stay indoors, have air conditioning on, use screens at doors.
Impregnated netting
Cover up with clothing and spray and soak clothing with repellant i.e. DEET.
How is malaria diagnosed in the UK?
Antigen testing
PCR
Blood films
What are the clinical features of malaria?
Fever, malaise, myalgia, headache, diarrhoea.
Anaemia, jaundice, renal impairment.
Severe - renal failure, DIC, acidosis, pulmonary oedema.
How is malaria treated?
Artemether compounds e.g. riamet
Quinine and doxycicline.
How is malaria prevented?
Bite avoidance
Chemoprophylaxis - mefloquine, doxycicline, malarone.
What are the clinical features of typhoid?
Fever, myalgia, headache, cough, abdominal pain, constipation, diarrhoea.
What are the symptoms of typhoid?
Diarrhoea or constipation
Abdominal pain, rectal bleeding, bowel perforation, headache, enteric encephalopathy, bacteraemia, relative bradycardia, rose spots - transient macular rash.
How would you come to a diagnosis in someone who has undifferentiated fever?
Travel history
Blood culture
Stool culture
Serology
What is the treatment of someone with salmonella typhi or paratyphi?
Quinolones, cephalosporins, azithromycin.
Which type of mosquito transfers dengue fever?
Aedes
What are the clincal features of dengue fever? What abnormal lab results would you have?
Headache, fever, retro-orbital pain, arthralgia/myalgia, rash, cough sore throat, nausea, diarrhoea.
Leukopenia, thrombocytopenia, transaminitis.
Give 2 examples of viral haemorrhagic fevers?
Ebola, yellow fever.
