Infections III: Bacterial resistance to antibiotics Flashcards
What are the 2 types of resistance that bacteria can acquire to antibacterial drugs?
- Inherent (natural) resistance
2. Acquired resistance
Describe inherent (natural) resistance
e.g. Gram negative bacteria = outer membrane provides a permeability barriers
Stops sufficient amounts of antibiotic entering cell to exert action
Describe acquired resistance
Most infections respond to a new antibiotic
Over time resistance is acquired and treatment fails
What causes acquired resistance?
Changes in the bacterial genome:
- Can be by mutation and selection = vertical evolution
- Or by exchange of genes between strains/species = horizontal evolution
How does an entire colony of bacteria becomes resistant (acquired)?
A group of bacteria, including a resistant variety, are treated with antibiotics
The non-resistant bacteria die
The resistant bacteria survive, multiply and become more common
Eventually the entire infection evolves into a resistant strain
List the 3 ways in which bacteria can swap genes to = horizontal evolution, acquired
- Conjugation
- Transduction
- Transformation
Give examples of how conjugation occurs between bacteria cells
Cell-cell contact
DNA crosses a sex pilus
Explain what transduction between bacterial cells is
Genes transported by bacterial virus
Explain what transformation between bacterial cells is
DNA acquired from environment
List the 4 mechanisms of resistance that bacteria use
- Conversion of active drug to inert product by enzyme
- Reduction in cellular permeability to antibiotic
- Changes in antibiotic target site = resistance OR acquisition of resistant form of target enzyme
- Altered metabolic pathway
Give an example of how an active drug can be converted to an inert product by bacteria to make them resistant
Gram positive and negative bacteria can produce beta-lactamase = converts penicillin to penicilloic acid = not antibacterial
How does a reduction in cell wall permeability make bacteria resistant?
Stops antibiotic reaching toxic levels in the cell
Can be:
- Change in cell wall/membrane
- Antagonism of antibiotic transport processes
- Generation of efflux pump
Give an example of how changes in the antibiotic target site results in resistance
S. aureus changes penicillin binding proteins on cell wall so it cannot have its effect
List 3 superbugs
MRSA = methicillin-resistant staphylococcus aureus
CRE
C. difficile
How does clostridum difficile become harmful?
Normally live in the digestive system
Not harmful because other bacteria keep it under control
Some antibiotics can kill this bacteria (normal flora)
Therefore C.diff can multiply and produce toxins = illness
Describe glycopeptide-resistant enterococci (GRE)
- Gram positive cocci
- Enteric - normally found in the digestive/urinary tract
- Intrinsically resistant to many antibiotics
- But has also acquired resistance by conjugation
What do glycopeptide-resistant enterococci (GRE) cause?
Wound infections
Bacteraemia (bacteria in blood, blood normally sterile)
Abdominal/pelvic infection
What are the current antibiotics to use to treat GRE?
Linezolid
Daptomycin
Tigecycline
Describe carbapenem-resistant enterobacteriaceae
Gram negative bacilli
Part of gut flora, also found in soil/water
Becoming resistant to most/all antibiotics
What are the current treatment options available to treat carbapenem-resistant enterobacteriaceae?
Polymyxins
Tigecycline
Fosfomycin
Aminoglycosides
What is tuberculosis?
Contagious lung infection
Mycobacterium tuberculosis
How is tuberculosis transmitted?
Aerosol
Describe what happens when person is infected with TB
First site of infection = lungs
Primary infection - can be resolved with local scarring
Dissemination (spreading) = miliary infection
List the symptoms of TB which affect the major organs of the body
Lungs = chronic cough, haemoptysis, fever, weight loss Brain = meningitis Kidney = fever, weight loss, hydronephrosis Spine = bone infections, vertebral collapse, nerve compression
How is TB diagnosed?
Bronchoscopy
Chest CT scan
Chest x-ray
How can TB be prevented?
Skin testing (PPD) Positive skin test = TB exposure but inactive infection Prompt treatment important BCG vaccination available in countries with high incidence of TB
Describe MRSA
Gram positive cocci
Acquires mecA gene - expression gives penicillin-binding protein variant, PBP2A
List 3 antibiotics currently used to treat MRSA
Vancomycin
Linezolid
Rifampicin
How is MRSA acquired in hospital?
Patients with opened wounds/weakened immune systems
Staff who do not follow proper sanitary procedures may inadvertently transfer from patient to patient
MRSA can survive on surfaces and fabrics
List 5 ways that resistance can be managed/prevented
Prudent antibiotic prescribing Hand hygiene Enhanced environmental cleansing Isolation Personal protective equipment
What is a broad spectrum antibiotic?
One which is effective against a wide range of disease-causing bacteria
Gram negative and positive
What is a narrow spectrum antibiotic?
An antibiotic only effective against specific families of (disease-causing) bacteria