ID - Antibiotic Resistance Flashcards
Mechanisms by which Abx work
1) inhibit cell wall synthesis (bacteria needs to have a cell wall)2) Inhibit DNA synthesis/funcion3) Inhibit tetrahydrofolate synthesis4) Inhibit protein synthesis
How do Abx work?
Either BacterioSTATIC or BacterioCIDALStatic - limit growth so immune system remove bacteria afterCidal - cause cell death whilst host cells remain undamaged (mammals dont have cell walls)
Examples of Bacteriostatic drugs
MacrolidesTetracyclineTrimethoprimSulphonamides
Examples of bacteriocidal drugs
PenicillinsCephalosporinsAminoglycosidesGlycopeptidesRifampicin
What is Time Dependent Killing
Agents whose activity depends on the amount of time the serum drug concentraction is above the Minimum Inhibitory Concentration (MIC)Regularly dosed to keep conc above MIC as much as possibleCan increase half life by adding drugs that reduce Abx elimination e.g probenecidEG - b-lactams, erythromicin, clindamicin, linez, vanc
What is Concentration Dependent Killing
Agents activity correlates with PEAK concentration.Higher doses are used with lower frequencyMay lead to toxicitiyAminoglycosides toxicity relate to TISSUE ACCUMULATION (e.g the trough level) not the peak level
Factors influencing Abx choice
1) Site of infection and likely organisms2) Severity of infection –> fulminant should use broad spec3) Their allergies4) Side effects and risk of c.diff5) Interactions - drug and PK (e.g. BBB)
6) Likelihood of resistant organisms Recent ABx LOS in hosptial/ICU Ward or other hospital Screening Local resistance patterns
Examples of drugs that inhibit cell wall synthesis
PenicillinsCephalosporinsGlycopeptides (Vacn/Teic)Polymixin E
Examples of DNA synthesis inhibtion
Metronidazole (a nitromidazole)Rifamycin (rifampicin)Quinolones (cipro)
Examples of THF inhibition
TrimethoprimSulphonamides - co-trimoxazoleDapsone
Examples of protein synthesis inhibitors
TetracyclineAminoglycc - gent, amikacinChloramphenicolMacrolides - eryth/clarith/azithClindamyinLinezolid (a oxazolidinone)
Examples of gram positive cocci
StaphStrep a - haemolytic - St.pneumoniae/viridians b - haem - group A - pyogenes groub B - agalactiaey - enterococci
Gram positive bacilli
ActinomycesBacillusClostridiaDiptheriaListeria
Gram neg cocci
Neiseria| Moraxella
Gram neg bacilli
Every thing else not covered
How does Hospital acquired MRSA infer resistance?
Meticillin resistance is due to the mecA gene which encodes for
an altered penicillin binding protein, PBP2’, consequently altering
the structure of the cell wall.
Classically used to be hospital acquired, but community acquired
strains are increasingly common, known as CA-MRSA.
What is meant by Panton-Valentine Leucocidin (PVL) producing Staphylococcus aureus?
- PVL is a toxin produced by <2% strains of Staphylococcus aureus.
- This is a pore forming toxin that destroys leucocytes and can be
produced by meticillin sensitive or meticillin resistant strains. - Usually responsible for skin and soft tissue infections like boils
and abscesses in healthy young adults. - Clinical spectrum extends to severelifethreatening infections such
as necrotising pneumonia, necrotising fascitis or purpura fulminans
(mimicking meningococcal sepsis). - PVL staphylococcal necrotising pneumonia is associated with
high mortality - the typical presentation is in a previously fit young
adult with recent flu-like illness with a high temperature (>39°C),
tachycardia, hypotension, marked leucopenia (due to the nature
of the toxin) and multi-lobular alveolar infiltrates on chest Xray
that often cavitate.
Can you name some of the types of beta haemolytic Streptococci?
Beta haemolytic Streptococci
* Gram positive cocci that occur in chains.
* So called because of the beta or complete clearing they produce around their colonies growing on blood agar.
* Classified into groups – A, B, C, D, F, G etc based on cell wall antigens.
Group A Streptococci
* Also known as Streptococcus pyogenes.
* Common cause of sore throat and skin infections like erysipelas,
but can cause severe invasive infections like toxic shock syndrome,
necrotising fasciitis and puerperal sepsis.
* Invasive Group A Streptococcal infections are increasing in
incidence and are associated with a mortality of up to 25%.
* Always sensitive to penicillin.
Group B Streptococci
* Common cause of neonatal infections and infections in diabetic patients.
Group C and G Streptococci
* Responsible for sore throat and skin and soft tissue infections, similar to Group A Streptococci.
* Lymphoedema is a risk factor for recurrent infections with Group G Streptococci.
How does VRE infer resistance?
Penicillin-binding protein mutations
Beta-lactamase production
Aminoglycoside modifying enzymes
Antibiotic drug efflux pumps
Alterations in cell wall components coded by transposons, described as Van A to F (A and B
most common)
Driven by widespread use of intravenous vancomycin resulting in sub-therapeutic levels in the
bowel lumen.
What are the ESCAPPM group?
Enterobacter cloacae and aerogenes, Serratia, Citrobacter, Acinetobacter, Proteus vulgaris,
Providencia, Morganella
Rapidly inducible production of beta-lactamase during therapy with cephalosporins, especially third generation agents
What are the ESBL group?
Extended
spectrum betalactamases
Escherichia coli, Klebsiella pneumoniae, other enterobacteriaciae
Genetically coded resistance to broad spectrum beta-lactam antibiotics: extended-spectrum
penicillins, third generation cephalosporins, Aztreonam
Co-resistance also often coded for co-trimoxazole, amnioglycosides and tetracyclines together,as well as separately for quinolones
What is the significance of Stenotrophomonas infection?
Intrinsic resistance to most beta-lactam antibiotics, including carbapenems and aminoglycosides due to two inducible enzymes: L1 (β-lactamase with broad activity against penicillins, carbapenems and cephalosporins) and L2 (cephalosporinase active against cephalosporins and monobactams) as well as enzyme modifiers and energy dependent efflux pumps
Involved in VAP, surgical site infections or CRBSI
Treated with Co-trimoxazole or fluoroquinolones (especially Moxifloxacin)
