Antibiotic Therapy 2

Question 1

What are DNA Gyrases ?

Answer 1

Essential bacterial enzyme for maintenance of DNA and its replicaton, transcription and recombniation
-Common target of antibiotics

Question 2

What are common targets of antibiotics ?

Answer 2

Cell wall
Ribosomes
DNA Replication
DNA Gyrases
Metabolic Pathways
Cell Membrane Function
Nucleic Acids
Folic Acid synthesis

Question 3

Describe protein synthesis inhibitors

Answer 3

-Antibiotic must cross cytoplasmic membrane to access target
-Bacterial ibosomes have structural differences from mammalian ribosomes.
-Binding interferes with protein/peptide synthesis; active processes stall, incomplete peptides released

Question 4

Describe bacteriostatic and cidal protein synthesis inhibiting antibiotics

Answer 4

Protein synthesis often resumes when the antibiotic is removed, most of antibiotics are bacteriostatic e.g. macrolides, tetracyclines
Aminoglycosides are bactericidal; binding to the ribosome is lethal

Question 5

What does bacteriostatic and bacteriocidal mean ?

Answer 5

-Bacteriostatic inhibit growth of bacteria
-Bactericidal kill bacteria

Question 6

What are the three most common classes of protein synthesis inhibitors ?

Answer 6

Aminoglycosides e.g. gentamicin (bacteriocidal)
Tetracyclines e.g. doxycylcine/minocycline (bacteriostatic)
Macrolides e.g. erthyromycin (bacteriostatic)

Question 7

What are aminoglycocides ?

Answer 7

Protein synthesis inhibitors
-Not absorbed from the gut – must be given intravenously IV or occasionally intramuscularly IM
-Bind to 30s ribosomes 30s inhibiting protein synthesis
-Irreversible binding & bactericidal (kills bacteria)
-Active mainly against Gram negative aerobic organisms e.g. coliforms & Pseudomonas aeruginosa & effective in hospital for treating serious (life-threatening) Gram-negative infection
-Excreted in the urine
Toxicity – causes damage to kidneys and VIIIth cranial nerve (deafness and dizziness), so need
to monitor blood levels of aminoglycosides complicating therapy

E.g. Gentamicin - Gentamicin use in severe life threatening scenarios

Question 8

What are tetracyclines

Answer 8

Protein synthesis inhibitors
-Actively transported into cell to binds to 30S subunit & prevents attachment of tRNA to acceptor sites. Stops chain elongation.
-Doxycycline more common/ replaced tetracycline
-Efficient absorption, less interaction with food/drugs, less frequent dosing (e.g. 2x per day)
-Broad spectrum; Useful against intracellular bacteria and atypical bacteria e.g .Chlamydia
-Used as alternative to Co-amoxiclav & penicillin allergy

e.g. tetracycline, minocycline & doxycycline

Restricted use in children, lower conc in GI so reduced microbiome risk and chance of AMR there - this is more unique in tetracyclines

Question 9

What are macrolides ?

Answer 9

Protein synthesis inhibitors
-Bind to 50s sun-unit
-Excreted via the liver, biliary tract and into the gut (not excreted in urine)
-Lipophilic antibiotics pass through cell membranes easily.

Bacteriostatic, commonly prescribed often for Penicillin allergy & intracellular pathogens

Question 10

What are examples of macrolides ?

Answer 10

Erythromycin (safe in pregenancy)
Azithromycin (slightly smaller spectrum but good Gram +ve coverage)
Clarithromycin (slightly greater activity & better Gram –ve coverage)

Pregenancy safety goes from top to bottom

Question 11

What are macrolide useful in treating ?

Answer 11

-They are useful for treating certain infections where intracellular bacteria “hide” from the host’s immune system e.g. Chalmydia/intracellular activity

Due to being lipophillic

Question 12

What are common antibiotics which target nucleic acids ?

Answer 12

Fluoroquinolones
Nitroimadazoles
Trimethoprim (+/- sulphonamide)
Rifampicin & Rifampin

Question 13

What do Fluoroquinolones work against ?

Answer 13

Gram negative & Gram positive

Tragte nucleic acids

Question 14

What are Rifampicin & Rifampin used for ?

Answer 14

Prevents transcription
Common use in combination therapy for Mycobacteria, Bacterial Meningitis prophylaxis

Traget nucleic acids

Question 15

What is Trimethoprim ?

Answer 15

Targets nucleic acids
-prevents synthesis of thymidine, some purines, methionine & glycine
-Activity against some Gram negative & some Gram positive bacteria.e.g. E. coli (Gram-negative), S.aureus, ß-haemolytic Streps (Gram-positive)
-Excreted via the urine
-Common for acute UTIs (urinary tract infections)
-Can be given on its own (orally)

Question 16

What do folic acid synthesis inhibitors do ?

Answer 16

key intermediate metabolism is blocked

Target Folic Acid synthesis

Folic acid vitamin required for synthesis of key cellular components

Question 17

What can trimethoprim be given with ?

Answer 17

Combination therapy with sulphamethoxazole (a sulphonamide) (orally or IV)
-Co-trimoxazole
-Alternative to Co-Amoxyclav as less C. diff risk or selection for resistance in empiric prescribing

Question 18

When is gentomicin used ?

Answer 18

A beta lactam is used. Bacteria produced beta lactamase so the beta lactams are not effective.
Carbapenen is used. Carbapenem is a tougher type of beta lactam and withstands beta lactamase. Bacteria produced carbapenemase so carpbapenem is not effective.
Gentomycin is used.beta

Question 19

What are quinilones ?

Answer 19

Target nucleic acids
-Mode of action – Direct damage to chromosome & indirectly inhibits DNA synthesis.
-Good intracellular activity, target in cytoplasm & cross cell membrane
-Bones, UTIs (excreted in urine), community acquired pneumonia,
-Ciprofloxacin (IV & Oral) largely Gram-negative activity
-Use as broad spectrum antibiotics; Now severely restricted to reduce the risk of C. difficile GI infection, especially in elderly patients

e.g. Ciprofloxacin, are bacteriocidal

Question 20

What are Nitroimadazoles

Answer 20

Target nucleic acids

-A gainst anaerobes & parasites/protozoa
-Drug activated by reduction process; Intracellular low Eh leads to reduction (found in strict anaerobes)
-Forms toxic intermediate that induces DNA strand breakage
-Resistance is extremely rare, but noted in some genera e.g. Bacteroides/Prevotella
-Adverse reactions limited provided alcohol is avoided, complaints of metallic taste, furred tongue,

e.g. Metronidazole (oral, & IV)

Question 21

Compare range between erythromicin, genatmicin and metronidazole

Answer 21

Question 22

Summarise key used of differnt antibiotics

Answer 22

Question 23

Why can antibiotics be prescribed in combination ?

Answer 23

-To cover a broad range of possible infecting organisms, e.g. for the treatment of pneumonia
-To prevent the development of resistance,e.g in the treatment of tuberculosis (TB)
-For the synergistic effect of combination (1+1 = 3), e.g in the treatment of some cases of endocarditis

Question 24

What types of antibiotics should never be combined ?

Answer 24

Never combine bacteriostatic & bactericidal e.g. Protein synthesis inhibition with cell wall antibiotics, cell wall synthesis has stopped as no enzymes/transporters etc being made.

Generally cell wall are bacteriocidal, protein synthesis are bacteriostatic

Question 25

Why should antibiotics be prescribed carefully ?

Answer 25

Nausea, vomiting, diarrhoea – common -all oral antibiotics disrupt the GI microbiome to some extent -may affect absorption of oral contraceptives Produce an infection -C. diff, Antibiotic sore mouth; Candida albicans a Fungus/Eukaryote AMR

Question 26

What is a side effect of gentamicin ?

Answer 26

renal & VIII nerve damage

Question 27

What is a side effect of Ciprofloxacin ?

Answer 27

Tendonitis, (especially if alongside corticosteroid) avoid use in pregnant or breast feeding women

Question 28

What is a side effect of Metronidazole ?

Answer 28

interacts with alcohol

Question 29

Which are high-risk restricted use antibiotics which increase risk of C. diff

Answer 29

The 4 “C” broad-spectrum antibiotics key risk factors -Cephalosporins -Co-amoxiclav -Ciprofloxacin -Clindamycin

Question 30

What is antibiotic sore mouth ?

Answer 30

Oral thrush -Candida albicans (Fungus/Eukaryote) growth secondary to antibiotic use

Question 31

What are different types of antibiotic prescribing ?

Answer 31

Presumptive Diagnosis (‘empiric’ prescribing) (without laboratory identification based on likely pathogens for infection under treatment Targeted prescribing (nature & extent) -Laboratory investigation - identification & sensitivity of pathogen

Question 32

What are considerations in deciding which antibiotic to prescribe ?

Answer 32

Drug choice, nature of infection, dose, route & frequency, allergy, interactions, compliance