L7: Introduction to Antibiotics and Resistance

Question 1

What are the different classifications of antimicrobials?

Answer 1

Antibiotics–> bacteria
Antiviral–> Viruses
Antifungal–> Fungi
Antiprotazoal–> Parasites

Question 2

What are the different classification of antibacterials?

Answer 2

Action–> Bactericidal (kill bacteria directly) or bacteriostatic (stop replication)
Spectrum–> Broad (works on wide range of bacteria) or Narrow (only works on a few bacteria)
Target site–> mechanism of action
Chemical structure–> antibacterial class

Question 3

How do you choose an antibiotic?

Answer 3

1- Is it active against target organism?
2- Does it reach the target site? e.g. cross BBB
3- Is it available in the right form? - Oral vs IV
4- What is the half life- determines dosing frequency? - short T1/2 given frequently, long T1/2 given less often
5- Does it interact with other drugs?
6- Is there toxicity issues? -Low enough dose to kill infection, too high toxic
7- Does it require therapeutic drug monitoring?

Question 4

How can antibiotic activity be measured?

Answer 4

Disc sensitivity testing
- spread bacteria over plate
- add discs soaked in antibiotics
- incubate 18hrs
- measure zonal clearance–> area around disc with no bacteria
Disc testing
- antibiotic diffuse out of disc across plate
- high conc close, low conc far
- bacteria grow
- reaches conc in agar where antibiotic too concentrated so bacteria stops growing
Broth microdilution
- increasing concentration of antibiotic placed in well
- add bacterial suspension
- leave overnight
- measure clearance
- MIC (minimum inhibitory clearance) –> minimum dose required to clear bacteria
E-test
- spread bacteria over plate
- add stripe with antibiotic at different grades
- leave overnight
- measure zonal clearance

Question 5

What are clinical breakpoint tables?

Answer 5

Standardises antibiotic testing over Europe and the UK
Allows comparison between laboratories
Chosen concentration of antibiotic which determines whether a species of bacteria is susceptible or resistant to an antibiotic.

Question 6

What are the different mechanisms of action of antibacterials?

Answer 6

Main target are to stop cell repair and replication 
1- Cell wall synthesis--> inhibit
2- Cell membrane synthesis --> inhibit
3- Protein synthesis--> inhibit
4- Nucleic acid synthesis --> inhibit,

Question 7

What are the different antibacterials that inhibit cell wall synthesis?

Answer 7

Beta-lactams (penicillin, cephalosporins, carbapenems and monobactams)
Glycopeptides (vancomycin and teicoplanin)

Question 8

What are the differences in action between beta lactams and glycopeptides?

Answer 8

Beta lactams

• Beta lactam ring
• Binds to penicillin binding protein
• Prevents crosslinking gycopeptide
• Weakens cell wall
• Osmotic lysis–> water moves in cell swells, lysis, bacteria dies

Glycopeptides

• Bind directly to glycopeptides (peptide cell wall precurosors)
• Prevent crosslinking

Question 9

What are the different types of resistance?

Answer 9

Intrinsic–> No target access for drug, resistance within the bacteria–> permanent
Acquired–> Acquires new genetic material or mutates–> permanent
Adaptive–> Stress response–> high levels of antibiotic–> becomes resistant–> remove antibiotic then re-add at later date no longer resistant

Question 10

What are the mechanisms of resistance?

Answer 10

Enzymatic modification or destruction of antibiotics
Enzymatic alteration of antibiotic targets
Mutation of bacterial target sites

Question 11

How does resistance come about?

Answer 11

Bacteria with chromosomal mutation
Antibiotic added–> all non-mutated killed
Mutated one survives and replicates

Question 12

What is horizontal gene transfer?

Answer 12

Plasmid with resistant gene passed to new bacteria by conjugation
Can be passed between species
New resistant cells–> replicate–> daughter cells with resistance

Question 13

What compounds are included in the B-lactam class?

Answer 13

Penicillins
Cephalosporins
Carbapenems
Monobactams

–> block cross linking of peptide chains during biosynthesis

Question 14

What are some of the different types of penicillins? Which bacteria do they mainly target?

Answer 14

Penicillin –> mainly active against Gram +ve, e.g. streptococci
Amoxicillin–> Activity against Gram -ve
Flucoxacillin–> Against Gram +ve and Gram -ve e.g. staphylcocci and streptococci

B lactamase inhibitor combinations

• -> Co-amoxiclav
• -> Piperacillin/tazobactam

Question 15

What are Beta-lactamase inhibitor combinations? Give a few example?

Answer 15

Contains a beta lactamase enzyme–> inactivates beta-lactmases released by bacteria–> prevents them being resistance

Co-amoxiclav–> Amoxicillin with clavulanic acid–> as well as others mentioned also targets anaerobes and gram negative bacteria

Piperacillin/tazobactam–> also targets gram negative and pseudomonas bacteria (go on to cause lung infections)

Question 16

What are the cephalosporins?

Answer 16

Gram +ve and -ve
Broad spectrum activity with no anaeobe activity
Increased targeting of -ve bacteria
Generations of antibiotics 1st, 2nd, 3rd, 4th…

Cetriaxone–> good activity in CSF (Neisseria meningitides)
Concern–> associated with C.difficile–> colitis types of infection

Question 17

What are some of the carbapenems? What are the key points about them?

Answer 17

Mostly Gram -ve
Broad spectrum (including anaerobes)
Generally safe in penicillin allergy
'Reserve' antibiotic 
Meropenem, ertapenem and imipenem

Question 18

What are the glycopeptides?

Answer 18

Vancomycin

• -> most against gram +ve
• -> IV formulations–> not absorbed by gut (oral no use)
• -> Therapeutic drug monitoring required
• -> Resistance to Staph rare
• -> Some Enterococci resistant

Teicoplanin
--> Gram +ve
--> Similar activity to vanomycin
--> easier to administer
Monitoring required but only needs administering once a day

Question 19

What are the difference classes of antibiotics that target proteins synthesis?

Answer 19

Tetracyclines + Doxycycline
Aminoglycosides
Macrolides

Question 20

What do tetracyclines and doxycyclines do, target and key characteristics?

Answer 20

Inhibit proteins synthesis
Gram +ve 
Broad spectrum (penicillin allergy)
Both oral 
Shouldn't be given to <12yrs or breastfeeding women (staining of developing teeth)

Active in atypical pathogens in pneumonia (colourless upon gram +ve and -ve staining)
Active against chlamydia and some protozoa

Question 21

What are the characteristic of aminoglycosides?

Answer 21

Inhibit protein synthesis
Most common--> gentamicin
Activity against gram -ve--> Reserved for severe gram -ve sepsis
Good activity in blood/urine 
Potentially nephrotoxic or ototocix 
Therapeutic drug monitoring required

Question 22

What are the characteristics of macrolides?

Answer 22

Inhibit protein synthesis
Mild gram +ve infection- alternative to penicillin 
Intracellular penetration 
Atypical respiratory pathogens
Erythromycin and clarithromycin

Question 23

What are the different classes of antibiotics that target nucleic acid synthesis?

Answer 23

Quinolones
Trimethoprim
Rifampicin

Question 24

What are the characterisitics of Quinolones?

Answer 24

Inhibit nucleic acid synthesis
Active against gram -ve
Atypical pathogens
Inhibit DNA gyrase
Commonest–> ciprofloxacin
Increased resistance and risk of C.difficile
Side effects–> tendinitis, rupture, aortic dissection, CNS defects

Question 25

What are the characterisitics of trimethopim and sulphonamides?

Answer 25

Inhibit nucleic acid synthesis
\+ve and -ve
Inhibitors of folic acid synthesis
Treat UTI 
Trimethopim combined with sulphamethoxazole
--> co-trimoxazole
--> treat pneumocystis jirovecii (disease of immunocompromised patients)
--> activity against MRSA

Question 26

What is a class of antifungals? How do they work?

Answer 26

Azoles–> active against yeast (+/- mold)
Inhibit cell membrane synthesis
Polyenes–> disrupt cell membrane

Question 27

What are some of the specific types of Azoles?

Answer 27

FUNGUS
Inhibits cell membrane synthesis 
Yeast and moulds
Fluconazole--> treat Candida (thursh)
Itra/vori/posaconazole--> treat fungal infections in immunocomprimised patients and Aspergillus (mold) in patients in hospital

Question 28

What are some of the specific types of Polyenes?

Answer 28

Nystain and amphotericin

• Inhibit cell membrane function
• Nsytain–> topical treatment of thrush
• Amphotericin–> IV treatment of systemic fungal infections

Question 29

What are two drugs that are used to treat viral infections?

Answer 29

Aciclovir–> Phosphorylated inhibits viral DNA polymerase
Treatment of Herpes simplex and Varicella zoster (chicken pox and shingles)
Oseltamivir–> Tamiflu
–> inhibits viral neuroaminidase
–> Influenza A and B –> Within 2-3 days of symptoms presenting

Question 30

What is metronidazole?

Answer 30

Antibacterial and antiprotozoal agent
Anaerobic bacteria
Protazoa: Amoebae (dysentery (diarrhoea lasting 14 days or systemic), Giardia (diarrhoea) and trichomonas (vaginitis- inflammation)