L16 - antimicrobial chemotherapy

Question 1

Centor criteria definition

Answer 1

gives an indication of the likelihood of a sore throat being due to bacterial infection

Question 2

Centor criteria

Answer 2

tender anterior neck glands, fever over 38 degrees, absence of cough

Question 3

IF 3/4 cantor criteria are met…

Answer 3

positive predictive value is 40-60%

Question 4

Absence of 3/4 cantor criteria…

Answer 4

fairly high negative predictive value of 80%

Question 5

Antiviral

Answer 5

a small molecule that works by blocking nucleic acid synthesis or binding a target site on a receptor or enzyme
can prevent through many different areas of virus lifecycle

Question 6

Antiviral usually used in…

Answer 6

treatment for humans in influenza A and B, and RSV

Question 7

Flu antiviral

Answer 7

neuraminidase inhibitors, competitive inhibitors of flus neuraminidase enzyme
binds to enzyme to prevent vision release therefore halted viral replication

Question 8

Flu antiviral effectiveness

Answer 8

shortens symptoms by half a day in adults compared to placebo, no reliable evidence for reducing risk being admitted to hospital or developing other conditions

Question 9

Flu antiviral NICE indication

Answer 9

used for people in at-risk groups, need to start treatment within 48 hours of first symptoms, or 36 within children

Question 10

Ribavirin

Answer 10

Nucleoside inhibitor, analogue of guanosine, stops viral RNA synthesis, good in vitro activity against RSV and studies show inconsistent results
reserved for immunocompromised children with severe RSV infection

Question 11

Ribavirin results

Answer 11

possible shorter duration, less need for ventilator or oxygen BUT TERATOGENIC
early use of inhaled ribavirin has been shown to reduce morbidity and mortality in adult bone marrow cell transplant recipients

Question 12

Antibiotic

Answer 12

molecules that work by binding a target site on a bacteria
target points of biochemical reactions crucial to bacteria survival
crucial binding site varies with antibiotic class

Question 13

S. Pneumoniae

Answer 13

gram positive cocci, alpha haemolytic, optocochia sensitive with over 90 serotypes. any age, can be severely ill with respiratory failure or sepsis
invasive pneumococcal disease

Question 14

S. Pneumonia treatment

Answer 14

B-lactam antibiotics i.e. amoxicillin, cefuroxime, cefotaxime
macrolides, clarithromycin, fluoroqinolines and ciproflaxacin

Question 15

H. Influenzae

Answer 15

Gram negative cocobacilli, originally thought to be influenza cause, encapsulated or un-encapsulated

Question 16

H. Influenza treatment

Answer 16

amoxicillin and calvulanic acid (co-amoxiclave)
tetracyclines - deoxycyclone
but not macrolides

Question 17

Staph. Aureus

Answer 17

may complicate recent influenza, ventilator-associated pneumonia

Question 18

Staph. Aureus treatment

Answer 18

Flucloxacillin, cerfuroxime, vancomycin, linezolid

Question 19

Klebsiella pneumoniae

Answer 19

fram-negative bacilli, enterobacteriacane
normal flora of mouth and intestines
effects mainly homeless, alcoholics and hospital-associated

Question 20

klebsiella pneumoniae treatment

Answer 20

Co-amoxiclav and cephalosporins

Question 21

Atypical pathogens

Answer 21

difficult to detect as they are intracellular, don’t grow on agar easily and need serology, need special antibiotics

Question 22

Atypical pathogen treatment

Answer 22

need special antibiotics as not susceptible to B-lactam and penicillin
macrolides, fluorquinolones and tetracyclines

Question 23

Hospital-acquired pneumonia early onset

Answer 23

under 5 days in hospital
organisms similar to CAP and anaerobes
Metronidazole or use a B-lactam with inhibitor of B-lacatamase i.e. co-amoxiclav or piperacillin-tazobactam

Question 24

Hospital-acquired pneumonia late onset

Answer 24

over 5 days
Staph. Aureus including methicillin-resistant
Pseudomonas aeruginosa
Acinetobcteria baumanii and klebsiella pneumoniae

Question 25

Pulmonary tuberculosis

Answer 25

curable, treat with at least 4 drugs for 6 months

Question 26

TB UK treatment

Answer 26

Rifampicin and isoniazid for 6 months or 12 if in CNS

Question 27

Directly observed therapy for TB

Answer 27

give meds in supervised fashion 3 or more a week

Question 28

Rifampicin

Answer 28

Enters bacilli in a conc-dependent manner, achieving steady-state conc. within 15 mins Drug binds to B-syunit of DNA-dependent RNA polymerase to form a stable drug-enzyme complex, suppressing chain formation in RNA synthesis

Question 29

Pyrazinamide

Answer 29

Activated to pyrazinoic acid under acidic conditions that likely prevail at edges of necrotic TB cavities where inflammatory cells produce lactic acid inhibition of fatty acid synthase type I leading to interference with mycelia acid synthesis binding to ribosomal protein S1 and inhibition of trans-translation reduction of intracellular pH disruption of membrane transport by HPOA

Question 30

Isonazid

Answer 30

enters bacilli by passive diffusion Drug is not directly toxic to bacillus but must be activated to its toxic form within the bacillus by KatG activated drug forms adducts with bacillary NAD+ and NADP+ that inhibit essential steps in mycelia acid synthesis and nucleic acid synthesis

Question 31

KatG

Answer 31

multifunctional catalase peroxidase

Question 32

Mycolic acid

Answer 32

part of cell wall

Question 33

Change of antibiotic target

Answer 33

bacteria changes the molecular configuration of antibiotic binding or masks it

Question 34

Destruction of antibitoi

Answer 34

destroyed or inactivated in susceptible host, inactivation through hydrolysis

Question 35

Prevent antibiotic access

Answer 35

modify the bacterial membrane porin channel size, numbers and selectivity

Question 36

Remove antibiotic from bacteria

Answer 36

Proteins in bacterial membranes act as an export or efflux protein - so level of antibiotic reduced

Question 37

How does resistance develop?

Answer 37

Bacterium which was previously susceptible obtains ability to resist activity of a particular antibiotic only certain strains of species will be reisstane can occur through spontaneous gene mutation

Question 38

Conjugation horizontal gene transfer

Answer 38

sharing of extra-chromosomal DNA plasmids i.e. MRSA

Question 39

Transduction horizontal gene transfer

Answer 39

insertion of DNA by bacteriophages

Question 40

Transformation horizontal gene transfer

Answer 40

picking up naked DNA

Question 41

TB resistance

Answer 41

drug unable to penetrate cell wall low pH renders drug inactive drug exported from cell before it reaches target anaerobic conditions lead to dormancy mutations in DNA repair genes Alteration of target protein structure prevents drug recognition alteration fo enzyme prevents conversion of pro-drug to active form

Question 42

Clostridium difficile 5Cs

Answer 42

Ciprofloxacin, Clindomucin, Cephalosporins, Co-amoxiclav, Carbapenems