Resistance In Gram +ve Flashcards
High priority pathogens (WHO list)
•enterococcus faecium
•staphylococcus aureus
Medium priority pathogens (WHO)
•streptococcus pneumoniae
Staphylococcus aureus resistance mechanism
•produce beta lactamase
•destroys penicillin
Enterococci resistance
•inherent resistance/tolerance
Streptococcus Pneumoniae resistance mechanism
•alter Penicillin binding proteins (PBP)
•reduced affinity for beta lactams
What is the functions of PBPs (penicillin binding proteins)
•provides cross linking between NAG and NAM in peptidoglycan cell wall
How do beta lactam antibiotics affect cell wall
•PBPs recognise D-ala-D-ala
•beta lactams mimic this
•PBPs bind beta lactams instead
•cross linking disrupts
What do beta lactamases do
•hydrolyse beta lactam ring between N and O
•creates penicillioc acid instead
•ineffective
What is the effective part of penicillins
•the beta lactam ring
What is flucloxacillin used for
•beta lactamase producing staphylococci
How does flucloxacillin work for staphylococcus but penicillin does not
•became resistant to penicillin
•bulky side chains added to make flucloxacillin prevent beta lactamase from working
What is the spectrum of flucloxacillin
•very narrow
•developed for beta lactamase producing staphylococcus
What is MRSA
Methicillin resistant staphylococcus aureus
How did MRSA begin
•methicillin introduced after penicillin resistance
•s aureus became resistant to methicillin and MRSA spread
Mechanism of MRSA resistance
•expression of PBP2a - resists methicillin
What encodes for PBP2a
•mecA on staphylococcal chromosomal cassette (SSCmec)
What is the target for methicillin resistance tests
•mecA gene on staphylococcal chromosomal cassette
What caused the MRSA epidemic
•clonal spread of S. Aureus strains containing SCCmec
•not individual mutations
What is SCCmec
•operon in MRSA
•encoding for mecA (PBP2a)
How did they reduce MRSA rates
•reporting and surveillance of bacteraemia
•infection control
•bacteraemia targets
Bacteraemia meaning
Presence of bacteria in the bloodstream
What can enterococci cause
•UTI
•bowel sepsis
What enterococci make up >90% of human isolates of enterococcus
•E. Faecalis
•E. Faecium
How are enterococci tolerant
•contain PBPs with low affinity for beta lactams and glycopeptides
•inhibited by clinical concentrations
•only killed if excess of MIC
Synergy meaning
Cooperation of >1 substances to produce combined effect better than if individual
How can enterococci tolerance be overcome
•synergy
•combine cell walls active agent with aminoglycoside
Antibiotic combination to treat enterococci
•gentamicin + penicillin or vancomycin
What is E. Faecium resistant to
Vancomycin
What are the 6 phenotypes for vancomycin resistance
•VanA-G
Clinically significant vancomycin resistant phenotypes
VanA and VanB
Most common vancomycin resistant phenotype
VanA
How many genes does the VanA/B phenotype contains
•7 genes in 2 clusters (VANA +VANB)
Describe VanA resistance
•high resistant to vancomycin and teicoplanin
•alter PBP - D-ala-D-ala becomes D-ala-D-lac
Describe VanB resistance
•variable resistance to vancomycin
•susceptible to teicoplanin
What is VRE
Vancomycin resistant enterococci
How does/did VRE evolve
High risk patients who have been treated with glycopeptides
*incorrect antibiotic use rather than infection control like MRSA
How to mediate VRE
Antibiotic stewardship
Main places/treatments where VRE evolves
•Haemodialysis
•Haematology
•Critical Care
Treatments for VRE
•quinupristin-dalfopristin
•linezolid
•daptomycin
•tigecycline
What is VRSA
•S. Aureus aquired VanA gene found in enterococci
How do pneumococcals become resistant to beta-lactams
•alter PBPs
•alters to PBP types - 2x, 2b, 1a
Six PBPs S. Pneumonia contains
•1a, 1b, 2a, 2b, 2x, 3
What is standard treatment for meningitis
•cephalosporin (ceftriaxone)
How are pneumococci resistant to cephalosporin
•alterations of PBP - 1a, 2x
Treatments for childhood meningitis - with previous antibiotic use or travel out of the UK in past 3 months
Vancomycin
