Antimicrobials

Question 1

Four classes of beta lactams

Answer 1

Penicillins

Monobactams

Cephalosporins

Carbapenems

Question 2

Narrow spectrum penicillins

Answer 2

Penicillin is mainly used for the treatment of Gram-positive pathogens such as streptococci, enterococci and anaerobes such as Clostridium spp

Phenoxymethylpenicllin V, oral

Benzylpenicillin, penicillin G, IV

Benzathine penicillin, IM, IV in system for 4 weeks

Procaine penicillin, IV

Question 3

Anti-staphylcoccal penicillins

Answer 3

Members include: flucloxacillin, dicloxacillin. These drugs are stable to beta - lactamase produced by staphylococci and are therefore particularly useful against most strains of S. aureus.

Question 4

Moderate spectrum penicillins

Answer 4

These agents, the aminopenicillins (amoxycillin and ampicillin), have greater activity than benzylpenicillin against common Gram-negative pathogens such as E. coli and H.influenzae.

Among patients with acute Epstein Barr virus infection (glandular fever), both drugs are similarly associated with the production of a prominent erythematous rash - however this does not indicate true allergy.

Question 5

Broad spectrum antibiotics

Answer 5

Piperacillin and ticarcillin are active against Pseudomonas aeruginosa, but are generally administered in combination with a second anti-pseudomonal drug such an aminoglycoside.

Ticarcillin is generally inferior to piperacillin in its coverage of Klebsiella species, as well as enterococci. Both drugs are reasonably expensive, especially piperacillin.

Question 6

Penicillin/beta-lactamase inhibitor combinations

Answer 6

amoxycillin (amoxycillin + clavulanate; Augmentin®)

ticarcillin (ticarcillin + clavulanate; Timentin®)

piperacillin (piperacillin + tazobactam; Tazocin®)

These have extended the spectrum of these drugs to include activity against S. aureus, anaerobes (e.g. B. fragilis) and strains of Gram-negative pathogens such as E. coli, Neisseria gonorrhoea and H. influenzae that are resistant to each of these penicillins alone.

Question 7

First generation cephalosporins

Answer 7

Cephalothin

Cephazolin

Cephalexin

Good gram positive activity

Gram negative activity against enterobacteriacae, klebsiella

Question 8

Second generation cephalosporins

Answer 8

Cefaclor and cefuroxime

Cefoxitin and cefotetan

Good gram positive cover

Improved gram negative cover, covers haemophilus, enterbacteriacae, klebsiella

Only cephalosporin group to cover anaerobes

Question 9

Third generation cephalosporins

Answer 9

Cefotaxime and ceftriaxone

Ceftazidime

No MSSA cover

Ceftazidime does not cover MSSA or streptococci

Cefotaxime and ceftriaxone will have good gram negative coverage as does second generation

Ceftazidime will cover pseudomonas

Question 10

Fourth generation cephalosporins

Answer 10

cefepime and cefpirome

Wider coverage than third generation

Will cover most gram positives including MSSA

Will cover most gram negatives including pseudomonas and ESCAPPM group

Question 11

Fifth generation cephalosporin

Answer 11

Ceftaroline

MRSA and penicillin non-susceptible Strept. pneumoniae activity (PNSP)

Wide gram negative and gram positive activity

Question 12

Carbapenems

Answer 12

Meropenem, ertapenem and imipenem

Action on wide spectrum of gram positive and negative bacteria

pseudomonas, ESCAPPMs, MRSA, Burkholderia cepacia and Stenotrophomonas maltophilia.

Meropenem has good CSF penetration

Question 13

Glycopeptides

Answer 13

Vancomycin and Teicoplanin

Glycopeptides include vancomycin and teicoplanin, both of which are active against a wide range of Gram-positive organisms including MRSA and methicillin-resistant S. epidermidis (MRSE).

Question 14

Aminoglycosides

Answer 14

Aminoglycosides (gentamicin, tobramycin, netilmicin, amikacin, streptomycin, neomycin and framycetin) are active against most Gram-negative pathogens including Pseudomonas aeruginosa, but have no substantive Grampositive activity as monotherapy.

Question 15

Macrolides

Answer 15

Macrolides include erythromycin, roxithromycin, azithromycin and clarithromycin. They have a wide spectrum of activity including Gram-positive cocci such as streptococci and staphylococci, as well as so-called “atypical” pathogens such as Legionella, Mycoplasma and Chlamydia spp.

They are also active against Bordetella pertussis (whooping cough), Corynebacteria and some strains of H. influenzae. Notably, they have no activity against enteric Gram-negative bacilli and resistance among S. pneumoniae and S. aureus is increasing.

Azithromycin and clarithromycin are newer agents and have longer half lives

Clarithromycin has Mycobacterium avium activity

Question 16

Tetracyclines

Answer 16

Tetracyclines have a broad range of activity against many Gram-positive and Gram-negative bacteria, mycoplasma, chlamydia, rickettsia and some spirochaetes.

Bacteriostatic

Emergence of resistance has limited the role of tetracyclines for treating some infections.

Photosensitive skin rash

IV tigecycline only efficicaous for MRSA, VRE, resistant mycoplasma (m. abscessus), poor choice for sepsis

Anaerobe and atypical activity, not pseudomonas activity

Question 18

Anti-folate agents

Answer 18

Trimethoprim and sulfamethoxazole both have anti-folate activity that impairs satisfactory DNA production. Except in combination with trimethoprim as cotrimoxazole,

sulphonamides used in the treatment of cerebral toxoplasmosis

Cotrimoxazole is a useful antibiotic for a broad range of indications, but especially for the treatment and prophylaxis of Pneumocystis carinii, the treatment of Listeria monocytogenes, Nocardia spp. and Stenotrophomonas maltophilia infections, and as an alternative for the treatment of infections due to “ESCAPPM” organisms.

Stevens-Johnson syndrome is one extreme of this allergic spectra, with marked muco-cutaneous desquamation and potentially fatal outcome. Patients with a history of sulpha allergy should not be given cotrimoxazole.

Question 19

Fluroquinolone

Answer 19

Fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin and enoxacin) broad range of activity against most Gramnegative bacteria (including Pseudomonas aeruginosa).

In addition, however, ciprofloxacin has excellent intra- cellular penetration and good oral availability, such that oral ciprofloxacin provides similar serum concentrations to intravenous ciprofloxacin.

Moxifloxacin extended Gram-positive spectrum to include activity against S. pneumoniae have recently been developed. Anaerobic, MSSA and atypical activity. No pseudomonas activity.

Side effects to fluoroquinolones include photosensitive skin rash, CNS toxicity (e.g. nightmares) and some agents interact with theophylline and caffeine.

Fluoroquinolones have been shown to damage the joints of immature animals and are therefore recommended to be used with caution in children under the age of 14 years.

Question 20

Rifamycins

Answer 20

Rifabutin and rifampicin

Largely active against gram positive species including MRSA and mycobacterium

Inducers of P450

Rifampicin needs to be used in combination with fusidic acid or ciprofloxacin to avoid resistant emergence

Question 21

Nitroimidazoles

Answer 21

Effective against gram positive and gram negative anaerobes

Anaerobic protozoa - trichomonas, giardia, entamoeba

C. diff infections

Effective in combination for intra-abdominal sepsis

Do not use with alcohol, disulfram-like activity occurs

Question 22

Lincosamides

Answer 22

Clindamycin

Most anaerobes and gram positive aerobes

Toxoplasma gondii activity

Question 23

Chloramphenicol and nitrofurantoin

Answer 23

Chrlorampenicol causes aplastic anaemia and dental issues in for unborn children

nitrofuratoin causes pulmonary fibrosis, polyneuropathy and acute hepatitis. Only used for UTIs

Question 24

Linezolid

Answer 24

Binds to the 50S subunit of bacterial ribosomes

Its main indication is treatment of methicillin-resistant Staph aureus, vancomycinresistant Staph aureus and vancomycin-resistant Enterococcus.

Adverse reactions include: myelo-suppression, polyneuropathy taste perversion and abnormal liver function.

Question 25

Cyclic lipopeptides

Answer 25

Daptomycin

Daptomycin retains potency against antibiotic resistant Gram positive bacteria, including isolates resistant to methicillin, vancomycin and linezolid.

Binds and depolarises bacterial cell membrane

Poor lung penetration

Question 26

Bacteriocidal agents

Answer 26

Beta-lactams

Fluroquinolones

Aminoglycosides

Glycopeptides

Question 27

Bacteriostatic agents

Answer 27

Anti-folate agents

Rifamycins

Colistins

Clindamycin

Tetracyclines

Macrolides

Fusidic acid

Question 28

Mechanisms of antibiotic resistance

Answer 28

1. Antibiotic inactivation
2. Alteration of antibiotic target sites
3. Decreased antibiotic permeability of the cell wall preventing drug access to its target
4. Active antibiotic efflux from the bacteria

Question 29

Types of beta-lactamases

Answer 29

• class A- plasmid mediated resistance (may be chromosomally encoded)
• class B - metalloenzymes NDM-1
• class C - Intrinsically resistant (Amp C, inactivate cephalosporins)
• class D - Oxacillin hydrolysing enzymes OXA-1

Question 30

Examples of altered antibiotic binding sites

Answer 30

• Altered DNA gyrase resulting in poor DNA gyrase activity
• Beta subunit RNA polymerase for rifampicin
• Altered penicillin binding protein sites in MRSA and penicillin resistant strep. pneumoniae