Pharmacology of Antibiotics Part 1

Question 1

Describe the general antimicrobial spectra.

Answer 1

Aerobic gram positive (enterococci, staph and strep)
Aerobic gram negative (enterobacter, salmonella)
Anaerobic (Bacteroides, Clostridium)
Atypical bacteria (Chlamydia, Mycoplasma)

Question 2

Which antibiotics have the best activity against atypical bacteria and why?

Answer 2

Tetracyclines, quinolones and macrolides have the best activity against atypical bacteria because they penetrate into host cells. These bacteria are intracellular.

Question 3

Define bacteriostatic. When are bacteriostatic antibiotics most effective?

Answer 3

Bacteriostatic drugs stop the growth of bacteria. They are more efficacious if given early when infectious burden is lower.

Question 4

Describe bactericidal drugs.

Answer 4

Kill bacteria. May be concentration dependent (a single, very large dose may eliminate infection) or be time-dependent (killing rate does not depend on concentration. Time within the therapeutic range is important).

Question 5

Give 3 examples of concentration dependent bactericidal antibiotics.

Answer 5

Aminoglycosides, quinolones and bacitracin.

Question 6

Give 5 examples of time-dependent bactericidal antibiotics.

Answer 6

Beta lactams, vancomycin, isoniazid, rifampicin and metronidazole.

Question 7

Give 5 examples of bacteriostatic antibiotics.

Answer 7

Chloramphenicol, clindamycin, macrolides, sulfonamides, tetracyclines and trimethoprim.

Question 8

What are the three types of antibiotics that target the cell envelope?

Answer 8

Betalactams, glycopeptides and daptomycin.

Question 9

What are the adverse effects of beta lactams?

Answer 9

Most common are hypersensitivity (urticarial drug rash and fever) and anaphylaxis.
Less common effects include C difficile colitis and seizures (occur at high doses of IV penicillin, imipenem and meropenem).

Question 10

What is clavulanic acid? What is it’s mechanism of action?

Answer 10

Clavulanic acid is a beta lactamase inhibitor that is often administered with amoxycillin. It has a beta lactam ring which is preferentially degraded by beta lactamases, thus increasing the plasma concentration of amoxycillin.

Question 11

What are the indications for use of penicillins?

Answer 11

Drug of choice for many infections, Eg bacterial meningitis, infections of bone, joints, skin, soft tissue, throat, bronchi and urinary tract.
Gonnorhea and syphilis.

Question 12

What are the adverse effects associated with penicillins?

Answer 12

Generally have very low toxicity, but may cause hypersensitivity or anaphylaxis.

Question 13

Describe the activity of narrow-spectrum penicillins.

Answer 13

Narrow spectrum penicillins are mainly active against gram positive organisms, but inactivated by beta lactamases.
Active against some gram negative, some anaerobes and some spirochetes.

Question 14

What is benzylpenicillin and benzathine penicillin.?

Answer 14

Penicillin G. Administered parenterally and is treatment of choice for susceptible infections if parenteral treatment is warranted. benzathine penicillin is the salt form of penicillin G, and Slowly releases penicillin G to provide low but long-lasting levels after a single dose. effective against bacteria with low MICs but requiring long exposure (e.g. syphylis).

Question 15

What is procaine penicillin?

Answer 15

IM preparation designed to extend the half life of benzyl penicillin. Provides blood levels for up to 24 hours, but this is only adequate for highly susceptible organisms.

Question 16

What is phenoxymethylpenicillin?

Answer 16

Penicillin V. Can be given orally due to acid stability, although food impairs absorption. Intrinsically less active than benzylpenicillin. Used for treating skin infections caused by strep pyrogenes.

Question 17

Which narrow-spectrum penicillins have anti staphylococcal activity? Why do they have this activity?

Answer 17

flucloxacillin and dicloxacillin. They have anti staphylococcal activity because they are penicillase (beta lactamase) resistant.

Question 18

Describe Flucloxacillin and its rare side effect. Compare with dicloxacillin.

Answer 18

Flucloxacillin is rarely associated with cholestatic jaundice, particularly in older patients on prolonged therapy. May occur after oral or IV administration and up to 6 weeks after treatment. it may last for months, can be irreversible and sometimes fatal.
Dicloxacillin appears to cause less irreversible hepatotoxicity but results in more infusion phlebitis, and may be preferable for oral therapy.

Question 19

How should oral dicloxacillin or flucloxacillin be taken?

Answer 19

Half to one hour before food. Food reduces the absorption.

Question 20

Describe aminopenicillins, including spectrum, combination therapy and its side effects.

Answer 20

Moderate to broad spectrum: amino group increases hydrophilicity and allows entry into bacterial cells through porins of some enteric gram negative rods (E coli, S enteric) and are drugs of choice for enterococcal infections (anaerobic).
Vulnerable to betalactamases. Spectrum dramatically broadened by combining amoxycillin with clavulanic acid.
Amoxycillin and clavulanate can cause diarrhoea and hepatotoxicity, which occur more frequently than with amoxicillin alone.

Question 21

Compare oral and parenteral ampicillin with amoxicillin.

Answer 21

Amoxicillin is better absorbed orally than ampicillin, and is not significantly affected by food, and also requires fewer oral doses per day.
When administered parenterally, they are equivalent.

Question 22

Which penicillins have broad spectrum and antipseudomonal activity? How can their spectra be extended?

Answer 22

Piperacillin and ticarcillin are the only penicillins with activity against P aeruginosa. This is because their polar side chain increases their ability to pass through porins. High doses are required because passage through porins is slow.
They are also active against most aerobic G+ and G-, and nearly all anaerobes (not C difficile).
Spectra can be extended by combining ticarcillin with clavulanate, and piperacillin with tazobactam.

Question 23

Which has the broadest activity: piperacillin or ticarcillin?

Answer 23

Piperacillin.

Question 24

What is tazobactam and how does it work?

Answer 24

Tazobactam is combined with piperacillin to extend its spectrum of action. this combination is one of the most powerful antibiotics available. Tazobactam is a beta-lactamase inhibitor.

Question 25

Discuss the structure of cephalosporins.

Answer 25

Have a betalactam ring. Side chains determine antibacterial, pharmacological and pharmacokinetic properties.

Question 26

What is the mechanism of action of cephalosporins and penicillins?

Answer 26

affect cell wall synthesis of bacteria by inhibiting cross linking between peptidoglycan layers.

Question 27

What are the indications for use of cephalosporins? How may their action be prolonged?

Answer 27

Meningitis, pneumonia and septicaemia. Action may be prolonged by probenecid, which reduces the tubular secretion of cephalosporins.

Question 28

What is a precaution for the use of cephalosporins? What are common adverse effects of their use?

Answer 28

Cross-sensitivity may occur between penicillins and cephalosporins. Adverse effects include nausea, vomiting, diarrhoea and C difficile-assosciated disease, and superinfection with Candida and Enterococcus especially with broad spectrum and prolonged treatment.

Question 29

What are the moderate spectrum cephalosporins? What bacteria are they effective against?

Answer 29

Cephalexin, cephalothin and cephazolin. Active against strep and staph (including those that produce beta lactamase).
Inactive against MRSA, enterococci and Listeria.
Gram negative spectra includes E coli and Klebsiella.

Question 30

What are the moderate spectrum cephalosporins with anti-haemophilus activity? Compare to general cephalosporins.

Answer 30

Cefuroxime and cefaclor. More stable than standard mod-spec cephalosporins to some G- beta-lactamases. More active against H influenzae.

Question 31

What are the moderate spectrum cephalosporins with anti anaerobic activity? Describe them. Which drug has superior activity against anaerobes compared to these cephalosporins?

Answer 31

Cefoxitin has significant anaerobic activity with 60% to 70% of Bacteroides fragilis being susceptible. It has a limited role for prophylaxis in bowel and gynaecological surgery, and for treatment of severe pelvic inflammatory disease.
Metronidazole provides superior cover against most anaerobes.

Question 32

Describe the broad spectrum cephalosporins.

Answer 32

Cefotaxime and ceftriaxone cover the majority of CA enteric G- rods.
Ceftriaxone has a long half life. The activity of these drugs against Bacteroides fragilis varies, but neither is as active as cefoxitin.
Less active against staph, and not useful against enterococci or MRSA.

Question 33

Describe the broad spectrum cephalosporins with antipsuedomonal activity.
How are they inactivated?

Answer 33

Ceftazidime and cefepime are effective against the majority of G- rods, including P aeruginosa.
Both are inactivated by the extended-spectrum beta lactamases, and ceftazidime may be inactivated by the chromosomal cephalosporinases.
Ceftazidime is less active, and cefepime is more active against G+ organisms. selection of one of these drugs for use in hospital will depend on cost.

Question 34

What are the three carbapenems? How are they inactivated?

What is their spectrum?

Answer 34

Imipenem, meropenem and ertapenem. Inactivated by metallo-beta-lactamases.
Carbapenems are important broad-spectrum drugs and their use should be reserved.

Question 35

What is cilistatin used for?

Answer 35

Cilistatin is combined with imipenem to prevent the inactivation of the antibiotic by a renal dipeptidase.
Cilistatin is a dipeptidase inhibitor/

Question 36

What has been the consequence of wide-spread use of carbapenems?

Answer 36

Increasing prevalence of infections due to MRSA, vancomycin-resistant enterococci, multi resistant G- organisms and C difficile.

Question 37

Describe the spectrum and use of monobactams and give examples.

Answer 37

Aztreonam: bactericidal. Inhibits cell wall synthesis by binding to penicillin-binding protein 3 of G- bacteria. May be given to people with severe penicillin hypersensitivity because of its lack of cross-reactivity with other beta-lactams.
Highly active against the majority of aerobic G- bact, including H influenza and Pseudomonas species.

Question 38

Describe vancomycin.

Answer 38

Glycopeptide designed to be given orally to kill bacteria in the gut. The molecule is too large to be absorbed. Gram negative bacteria are not susceptible.

Question 39

Describe the mechanism of action of glycopeptides, their spectrum.

Answer 39

Vancomycin and teicoplanin inhibit cell wall synthesis by inhibiting peptidoglycan formation.
Active against a wide range of G+ organisms (nearly all staph and strep). Some enterococci have developed resistance.
Not active against G- bacteria.

Question 40

Describe the use of glycopeptides.

Answer 40

Important in the treatment/prophylaxis of infection with MRSA or MR coagulase-negative staph.
Treatment of severe infection in patients with penicillin hypersensitivity, and in meningitis due to penicillin-resistant Strep pneumoniae.

Question 41

Why should vancomycin use be reserved?

Answer 41

Vancomycin has been given orally to treat antimicrobial-assosciated diarrhoea, but emergence of resistance in enterococci makes it essential to reserve it for use in severe cases that are unresponsive to metronidazole.

Question 42

Describe the pharmacokinetics of vancomycin?

Answer 42

Poorly absorbed (give by IV infusion or injection). Oral vancomycin is only used to treat C difficile-related colitis.

Question 43

Why must vancomycin be given by slow IV infusion? How can the effect be reduced?

Answer 43

To avoid anaphylactoid reaction “red man syndrome”.

Can treat with antihistamines, or using teicoplanin instead of vancomycin.

Question 44

What is a major adverse effect of vancomycin?

Answer 44

May cause hearing loss, especially when administered with an amino glycoside.

Question 45

What are the categories of Abx that inhibit bacterial cell wall synthesis?

Answer 45

Beta-lactams: Penicillins, carbapenems, monobactams, cephalosporins, glycopeptides