Antimicrobial agents 110821

Question 1

name some beta lactam antibiotics

Answer 1

penicillins
cephalosporins
carbapenems

Question 2

How do beta lactams work

Answer 2

bactericidal. Inhibit cell wall synthesis by being a substrate to penicillin binding protein

Question 3

Why might beta lactams not be effective

Answer 3

if the cell wall has already been formed or if the bacteria does not have a peptidoglycan cell wall e.g. mycoplasma, clamydia

Question 4

Describe how penicillin works

Answer 4

works against Gram +ve streptococci, clostridia

broken down by beta lactamases which are produced by staph aureus etc

Question 5

Describe amoxicillin

Answer 5

Broad spectrum to enterococci and gram -ve

Question 6

Flucloxacillin

Answer 6

effective against STAPH AUREUS as it is NOT broken down by beta lactamase produced by SA

Question 7

Piperacillin

Answer 7

broad spectrum (pseudomonas, non-enteric gram -ve, broken down by beta lactamase

Question 8

Clavulanic acid and tazobactam

Answer 8

beta lactamase inhibitors,

Question 9

Name some examples of Cephalosporins

Answer 9

Ceforoxime, ceftriaxone, ceftazidime

Question 10

What is the significance of the generations of cephalosporins

Answer 10

Increasing activity against gram negative bacilli

Question 11

ceftazidime vs. ceftriaxone vs. cefotaxime

Answer 11

ceftriaxone (associated with c. diff, treat meningitis, no cover against pseudomonas); ceftazidime (activity against pseudomonas), cefotaxime (paediatric ceftriaxone)

Question 12

Do cephalosporins work against ESBL producing organisms

Answer 12

No they don’t - use carbapenems

Question 13

what are Carbapenems used for

Answer 13

Stable against ESBL producing organisms

Question 14

Examples of CARBAPENEMS

Answer 14

Meropenem, imipenem, ertapenum

Question 15

What are examples of beta lactams

Answer 15

penicillins, cephalosporins, carbapenems, monobactams

Question 16

Key features of beta lactams

Answer 16

o Relatively non-toxic
o Renally excreted so decrease dose if renal impairment
o Short T1/2 (many are type 2 drugs so aim to maximise the time > MIC)
o Will not cross BBB
o Cross allergenic – penicillin has 10% cross reactivity with cephalosporins and carbapenems

Question 17

Glycopeptides

Answer 17

Active against gram +ve, large molecules so unable to penetrate gram -ve.
Slowly bactericidal
nephrotoxic

Question 18

Important uses of glycopeptides

Answer 18

MRSA, c dif

Question 19

Why must you monitor glycopeptides

Answer 19

nephrotoxic

Question 20

Examples of glycopeptides

Answer 20

Vancomycin
Teicoplanin
Telavancin

Question 21

Give examples of antibiotics that inhibit protein synthesis

Answer 21

aminoglycosides, tetracyclines, macrolides, cloramphenicol, oxazolidinones

Question 22

Aminoglycosides, examples, MOA

Answer 22

• Aminoglycosides – gentamicin, amikacin, tobramycin
o Bind to amino-acyl site of 30s ribosome subunit
o Rapid, concentration-dependent bactericidal
o Require specific transport mechanisms to enter
 Accounts for some intrinsic resistance
o Ototoxic and nephrotoxic – monitor levels
o Gentamicin and tobramycin are particularly active against pseudomonas aeruginosa
o Synergistic combination with beta lactams
 Endocarditis treatment, pneumonia
o No activity against anaerobes

Question 23

Tetracyclines

Answer 23

o Broad spectrum, activity against intracellular pathogens – chlamydia, rickettsia, mycoplasma
o Bacteriostatic (stops bacteria from reproducing)
o Widespread resistance now
o Deposited in growing bone
 Don’t give to children, pregnant women
o SE: photosensitivity rash (summer effect)
 Particularly doxycycline

Question 24

Which protein synthesis inhibitor should you NOT give to children and pregnant women

Answer 24

Tetracyclines as it deposits in growing bone

Question 25

Macrolides

Answer 25

o Bacteriostatic
o Useful agent for treating mild staphylococcal or streptococcal infections in pen-allergic patients
o Active against campylobacter species, legionella, pneumophilia
o Newer agents include clarithromycin and azithromycin due to a better half-life
o Little activity against gram -ve bacteria (membrane)
o Useful to inhibit toxins produced by bacteria

Question 26

Cloramphenicol

Answer 26

o Bacteriostatic
o Broad antibacterial activity
o Rarely used apart from eye preparations
 Risk of aplastic anaemia
 Risk of grey-baby syndrome in neonates because of inability to metabolise the drug

Question 27

Oxazolidinoes

Answer 27

o Highly active against gram +ve (MRSA & VRE)
o Not active against most gram -ve

o Expensive, may cause thrombocytopenia & optic neuritis; should only be used with micro/ID approval
o Binds to 23S component of 50s subunit  prevents formation of a functional 70s initiation complex

Question 28

Which antibiotics inhibit DNA synthesis

Answer 28

Quinolones and nitromidazoles

Question 29

Nitromidazoles

Answer 29

o Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage
o Rapidly bactericidal
o Active against anaerobic bacteria and protozoa (Giardia)
o Nitrofurans are related compounds (nitrofurantoin is good for cystitis and lower UTIs)

Question 30

Quinolones

Answer 30

o Act on alpha unit of DNA gyrase, bactericidal
o Broad antibacterial activity versus gram -ve (pseudomonas aeruginosa)
o Newer agents (levofloxacin, moxifloxin) better against gram +ve and intracellular bacteria (Chlamydia spp.)
o Well absorbed after PO administration (good bioavailability)
o Use for UTI, pneumonia, atypical pneumonia, bacterial gastroenteritis
o Lower your seizure threshold, also causes achilles tendonitis

Question 31

Rifamycin

Answer 31

• Rifamycins – rifampicin and rifabutin
o Inhibits protein synthesis by binding to DNA-dependent RNA polymerase, inhibiting initiation
o Bactericidal
o Active against mycobacteria and chlamydia
o Interactions with other drugs metabolised in the liver (OCP) and so need to monitor LFTs
o Turns secretions orange (urine and contacts) – can check compliance

o Rifampicin resistance (never used as a single):
 Resistance due to chromosomal mutation
 Causes single amino acid change in beta subunit of RNA polymerase which fails to bind rifampicin

Question 32

Inhibitors of folate metabolism include

Answer 32

• Sulphonamides
o Resistance is common
o Combination of sulphamethoxazole + trimethoprim (co-trimoxazole) is important in treating pneumocystis jiroveci pneumonia (PCP – HIV-defining disease)

• Diaminopyrimidines – trimethoprim
o Used as treatment for community acquired UTIs

Question 33

How does MRSA and strep pneumoniae have resistance to flucloxacillin

Answer 33

target modification

Question 34

How do ESBLs have resistance

Answer 34

enzyme modification/iniactivation