ID - Antibiotic Resistance

Question 1

Mechanisms by which Abx work

Answer 1

1) inhibit cell wall synthesis (bacteria needs to have a cell wall)2) Inhibit DNA synthesis/funcion3) Inhibit tetrahydrofolate synthesis4) Inhibit protein synthesis

Question 2

How do Abx work?

Answer 2

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)

Question 3

Examples of Bacteriostatic drugs

Answer 3

MacrolidesTetracyclineTrimethoprimSulphonamides

Question 4

Examples of bacteriocidal drugs

Answer 4

PenicillinsCephalosporinsAminoglycosidesGlycopeptidesRifampicin

Question 5

What is Time Dependent Killing

Answer 5

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

Question 6

What is Concentration Dependent Killing

Answer 6

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

Question 7

Factors influencing Abx choice

Answer 7

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

Question 8

Examples of drugs that inhibit cell wall synthesis

Answer 8

PenicillinsCephalosporinsGlycopeptides (Vacn/Teic)Polymixin E

Question 9

Examples of DNA synthesis inhibtion

Answer 9

Metronidazole (a nitromidazole)Rifamycin (rifampicin)Quinolones (cipro)

Question 10

Examples of THF inhibition

Answer 10

TrimethoprimSulphonamides - co-trimoxazoleDapsone

Question 11

Examples of protein synthesis inhibitors

Answer 11

TetracyclineAminoglycc - gent, amikacinChloramphenicolMacrolides - eryth/clarith/azithClindamyinLinezolid (a oxazolidinone)

Question 12

Examples of gram positive cocci

Answer 12

StaphStrep a - haemolytic - St.pneumoniae/viridians b - haem - group A - pyogenes groub B - agalactiaey - enterococci

Question 13

Gram positive bacilli

Answer 13

ActinomycesBacillusClostridiaDiptheriaListeria

Question 14

Gram neg cocci

Answer 14

Neiseria| Moraxella

Question 15

Gram neg bacilli

Answer 15

Every thing else not covered

Question 16

How does Hospital acquired MRSA infer resistance?

Answer 16

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.

Question 17

What is meant by Panton-Valentine Leucocidin (PVL) producing Staphylococcus aureus?

Answer 17

• 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.

Question 18

Can you name some of the types of beta haemolytic Streptococci?

Answer 18

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.

Question 19

How does VRE infer resistance?

Answer 19

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.

Question 20

What are the ESCAPPM group?

Answer 20

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

Question 21

What are the ESBL group?

Answer 21

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

Question 22

What is the significance of Stenotrophomonas infection?

Answer 22

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)