Micro - Antimicrobials (Antimicrobials inhibiting Protein Synthesis)

Question 1

How do protein synthesis inhibitors affect bacteria and spare humans?

Answer 1

Specifically target smaller bacterial ribosome (70S, made of 30S and 50S subunits), leaving human ribosome (80S) unaffected

Question 2

Which antimicrobials affecting protein synthesis are 30S versus 50S inhibitors?

Answer 2

30S inhibitors: A = Aminoglycosides [bactericidal], T = Tetracyclines [bacteriostatic]; 50S inhibitors: C = Chloramphenicol, Clindamycin [bacteriostatic}, E = Erythromycin (macrolides) [bacteriostatic], L = Linezolid [variable]; Think: “Buy AT 30, CCEL (sell) at 50”

Question 3

Again, what are the 30S inhibitors? Which are bacteriostatic versus bactericidal?

Answer 3

Aminoglycosides (bacteriocidal), Tetracyclines (bacteriostatic)

Question 4

Again, what are the 50S inhibitors? Which are bacteriostatic versus bactericidal?

Answer 4

Chloramphenicol [bacteriostatic], Clindamycin [bacteriostatic], Erythromycin (macrolides) [bacteriostatic], Linezolid [variable]

Question 5

What are 5 examples of aminoglycosides?

Answer 5

(1) Gentamicin (2) Neomycin (3) Amikacin (4) Tobramycin (5) Streptomycin; Think: “‘Mean’ (aMINoglycoside) GNATS caNNOT kill anaerobes”

Question 6

Are aminoglycosides bacteriostatic or bactericidal? What is their specific mechanism?

Answer 6

Bactericidal; Inhibit formation of initiation complex and cause misreading of mRNA. Also block translocation; Think: “A initiates the Alphabet”

Question 7

What do aminoglycosides require for uptake, and what is a clinical implication/consequence of this?

Answer 7

Require O2 for uptake; therefore ineffective against anaerobes

Question 8

What is the coverage/clinical use of aminoglycosides?

Answer 8

Severe gram-negative rod infections

Question 9

With what other type of antimicrobials are aminoglycosides synergistic?

Answer 9

Synergistic with Beta-lactam antibiotics

Question 10

Which aminoglycoside is used for bowel surgery?

Answer 10

Neomycin for bowel surgeryh

Question 11

What are 4 toxicities to associate with aminoglycosides?

Answer 11

(1) Nephrotoxicity (especially when used with cephalosphorins) (2) Neuromuscular blockade (3) Ototoxicity (especially when used with loop diuretics) (4) Teratogen; Think: “‘Mean’ (aMINoglycoside) GNATS caNNOT kill anaerobes”

Question 12

Using aminoglycosides along with what other antimicrobials makes them especially nephrotoxic?

Answer 12

Nephrotoxicity (especially when used with cephalosporins)

Question 13

Using aminoglycosides along with what other drug class makes them especially ototoxic?

Answer 13

Ototoxicity (especially when used with loop diuretics)

Question 14

What is the mechanism of resistance against aminoglycosides?

Answer 14

Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation

Question 15

What are 3 examples of tetracyclines?

Answer 15

(1) Tetracycline (2) Doxycycline (3) Minocycline

Question 16

Are tetracyclines bacteriostatic or bactericidal? What is their specific mechanism?

Answer 16

Bacteriostatic; Bind to 30S and prevent attachment of aminoacyl-tRNA

Question 17

What part of the body has limited penetration of tetracyclines?

Answer 17

Limited CNS penetration

Question 18

In what particular patient population can tetracycline be used, and why?

Answer 18

Doxycycline is fecally eliminated and can be used in patients with renal failure

Question 19

What are 3 things that you should not take with tetracyclines, and why?

Answer 19

Do not take with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-containing preparations because divalent cations inhibit its absorption in the gut

Question 20

What is the bacterial coverage of tetracyclines? For what medical condition are tetracyclines also used?

Answer 20

Borrelia burgdorferi, M. pneumoniae. Drug’s ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia. Also used to treat acne.

Question 21

What are 4 toxicities associated with tetracylines?

Answer 21

(1) GI distress (2) Discoloration of teeth in children (3) Inhibition of bone growth in children (4) Photosensitivity

Question 22

In what medical condition/patient population are tetracyclines contraindicated?

Answer 22

Contraindicated in pregnancy

Question 23

What is the mechanism of resistance against tetracyclines?

Answer 23

Decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps

Question 24

What are 3 examples of macrolides?

Answer 24

(1) Azithromycin (2) Clarithromycin (3) Erythromycin

Question 25

What is the specific mechanism of macrolides? Are they bacteriostatic or bactericidal?

Answer 25

Inhibit protein synthesis by blocking translocation ("macroSLIDES"); bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic

Question 26

What is the coverage/clinical use of Macrolides?

Answer 26

Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STDs (for Chlamydia), and gram-positive cocci (streptococcal infections in patients allergic to penicillin)

Question 27

What are 5 toxicities to associated with macrolides?

Answer 27

MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT, acute Cholestatic hepatitis, Rash, eOsinophlia

Question 28

What 2 substances increase in serum concentration upon macrolide use?

Answer 28

Increases serum concentration of the theophyllines, oral anticoagulants

Question 29

What is the mechanism of resistance against macrolides?

Answer 29

Methylation of 23 rRNA-binding site prevents binding of drug

Question 30

What is the specific mechanism of chloramphenicol? Is it bacteriostatic or bactericidal?

Answer 30

Blocks peptidyltransferase at 50S ribosomal subunit; Bacteriostatic

Question 31

What are clinical uses for chloramphenicol?

Answer 31

Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and Rocky Mountain spotted fever (Rickettsia rickettsii)

Question 32

What are the limitations of chloramphenicol? Where is it used, and why?

Answer 32

Limited use owing to toxicities but often still used in developing countries because of low cost.

Question 33

What are 3 toxicities associated with chloramphenicol? What are details to remember about each of these?

Answer 33

(1) Anemia (dose dependent) (2) Aplastic anemia (dose independent) (3) Gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase)

Question 34

What is the mechanism of resistance against chloramphenicol?

Answer 34

Plasmid-encoded acetyltransferase inactivates the drug

Question 35

What is the specific mechanism of clindamycin? Is it bacteriostatic or bactericidal?

Answer 35

Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic.

Question 36

What is the clinical use/coverage of clindamycin?

Answer 36

Anaerobic infections (e.g., Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive Group A streptococcal (GAS) infection.

Question 37

Compare/Contrast clindamycin and metronidazole in terms of clinical use/coverage.

Answer 37

Clindamycin treats anaerobes above the diaphragm vs. metronidazole (anaerobic infections below diaphragm)

Question 38

What are 3 toxicities to associate with clindamycin?

Answer 38

(1) Pseudomembranous colitis (C. difficile overgrowth) (2) Fever (3) Diarrhea