Bacteria and antibiotics

Question 1

Gram positive vs gram negative

Outer membrane?

Answer 1

Gram negative

Question 2

Gram positive vs gram negative

Techoic acid?

Answer 2

Gram positive

Question 3

Gram positive vs gram negative

Capsule?

Answer 3

Some of both

Question 4

Gram positive vs gram negative

Lipopolysaccharide (endotoxin)

Answer 4

Gram negative

Question 5

Gram positive vs gram negative

Internal cell membrane and cell wall made of peptidoglycan?

Answer 5

Both

Question 6

Gram positive vs gram negative

Thinner cell wall?

Answer 6

Gram negative

Question 7

Gram positive vs gram negative

Periplasmic space?

Answer 7

Gram negative

Question 8

Antibiotics that inhibit bacterial cell wall synthesis

Answer 8

B-lactam antibiotics

block the cross-linking of PG units by inhibiting the peptide bond formation reaction catalyzed by transpeptidases, which are also known as penicillin-binding proteins (PBP)

Question 9

B-lactam antibiotics examples

Answer 9

penicillin
Cephalosporin
Carbapenems (imipenem, meropenem)

resistance to these antibiotics is mediated by bacterially synthesized B-lactamase enzymes that destroy the B-lactam ring

Question 10

Clavulanic acid and sulbactam?

Answer 10

inhibitors of B-lactamase, thereby reducing resistance of bacterial species to the penicillins

Question 11

ceftriaxone

Answer 11

third generation cephalosporin
more resistant to beta-lactamases than narrow spectrum penicillins

Parenteral, broad spectrum beta-lactams such as ceftriaxone are the preferred antibiotics for initial empiric therapy of pyelonephritis caused by most pathogens (e.g. E. coli, Proteus, Klebsiella).

Question 12

peptidoglycan

Answer 12

a covalently cross-linked polymer matrix composed of peptide-linked β-(1–4)-N-acetyl hexosamine

The mechanical strength afforded by this layer of the cell wall is critical to a bacterium’s ability to survive environmental conditions that may alter prevailing osmotic pressures; of note, the degree of PG cross-linking can be correlated with the structural integrity of the cell

Question 13

Maintenance of the peptidoglycan layer

Answer 13

Maintenance of the PG layer is accomplished by the activity of transglycosylase and transpeptidase enzymes, which add disaccharide pentapeptides to extend the glycan strands of existing PG molecules and cross-link adjacent peptide strands of immature PG units, respectively

Question 14

Why treat with cell wall synthesis inhibitor

Answer 14

Successful treatment with a cell wall synthesis inhibitor can result in changes to cell shape and size, induce cellular stress responses, and culminate in cell lysis

Question 15

classes of antibiotics that interfere with specific steps in homeostatic cell wall biosynthesis.

Answer 15

β-lactams and glycopeptides

Question 16

MOA Beta lactams

Answer 16

binds to penicillin-binding proteins (PBPs). This binding inhibits transpeptidation. Crosslinked peptidoglycan chains form the bacterial cell wall.

block the cross-linking of PG units by inhibiting the peptide bond formation reaction catalyzed by transpeptidases, which are also known as penicillin-binding proteins (PBP)

This inhibition is achieved by penicilloylation of a PBP’s transpeptidase active site –- the β-lactam drug molecule (containing a cyclic amide ring) is an analog of the terminal D-alanyl-D-alanine dipeptide of PG, and acts a substrate for the enzyme during the acylation phase of cross-link formation –- which disables the enzyme due to its inability to hydrolyze the bond created with the now ring-opened drug

Question 17

Glycopeptide antibiotics example

Answer 17

Vancomycin

Glycopeptides (vancomycin) is a large bulky molecule that can’t cross the outer membrane of gram-negative bacteria, such as E. coli.

Question 18

MOA glycopeptide antibiotics

Answer 18

inhibit PG synthesis through binding with PG units (at the D-alanyl-D-alanine dipeptide) and by blocking transglycosylase and transpeptidase activity

generally act as steric inhibitors of PG maturation and reduce cellular mechanical strength, although some chemically-modified glycopeptides have been shown to directly interact with the transglycosylase enzyme

Question 19

β-lactams vs glycopeptides

Answer 19

β-lactams can be used to treat Gram-positive and Gram-negative bacteria, whereas glycopeptides are effective only against Gram-positive bacteria due to low permeability

Question 20

MOA Fosfomycin

Answer 20

Inhibit the synthesis of individual PG units

It is a structural analog of phosphoenolpyruvate, and inhibits an enzyme (enolypyruvate transferase) involved in a very early intracellular stage of cell wall synthesis. It is used for treating uncomplicated UTIs (and not pyelonephritis).

Question 21

MOA Bacitracin

Answer 21

Inhibit the transport of individual PG units

Question 22

Daptomycin?

Answer 22

Lipopeptide: affect structural integrity via their ability to insert into the cell membrane and induce depolarization.

not effective against gram-negative bacteria

Question 23

Transglycosylase activity?

Answer 23

add disaccharide pentapeptides to extend the glycan strands of existing PG molecules

Question 24

50S ribosome inhibitors

Answer 24

include the macrolide (e.g., erythromycin), lincosamide (e.g., clindamycin), streptogramin (e.g., dalfopristin/quinupristin), amphenicol (e.g., chloramphenicol) and oxazolidinone (e.g., linezolid) classes of antibiotics86, 87.

In general terms, 50S ribosome inhibitors work by physically blocking either initiation of protein translation (as is the case for oxazolidinones), or translocation of peptidyl-tRNAs, which serves to inhibit the peptidyltransferase reaction that elongates the nacent peptide chain.

Question 25

30S ribosome inhibitors

Answer 25

include the tetracycline and aminocyclitol families of antibiotics.

aminoglycosides, tetracyclines & tigecycline

Question 26

Cross reactivity among b-lactams

Answer 26

Drugs that start with “cef” or “ceph” are cephalosporins. These drugs have a 6-membered ring structure fused to the beta-lactam ring (as compared to penicillins that have a 5-member ring attached to the beta-lactam core). Cephalosporins are structurally different enough than penicillins to have only ~1-2% cross-reactivity. This risk of cross-reactivity is acceptable when the patient has a history of a minor allergic-like reaction, but the risk is generally considered NOT acceptable if the patient has a history of an anaphylactic reaction to another beta-lactam antibiotic.

shares a common mechanism, but would be very unlikely to produce a similar allergic reaction

Question 27

Penicillin is administered IV. T/F?

Answer 27

false. Penicillin is given orally

Question 28

Side effect of vancomycin

Answer 28

Red man syndrome / Red neck syndrome

hypotension, as well as marked flushing & itching over the upper portion of his chest, neck and face.
These symptoms result from histamine release when vancomycin is infused too rapidly.

Question 29

Side effect of linezolid

Answer 29

This drug can inhibit monoamine oxidase (MAO) and produce a serotonin-excess or tyramine-excess type reaction when drugs or foods are consumed that elevate these compounds. This reaction could elevate blood pressure

Question 30

Side effect of daptomycin

Answer 30

affecting skeletal muscle, producing myalgia & weakness with increased CPK (creatine kinase) levels.

Question 31

Kirby-Bauer test

Answer 31

disc-diffusion test.
Bacterial sensitivity to antibiotics can be evaluated by the disc-diffusion (Kirby-Bauer) test where thin filter-paper wafers impregnated with antibiotics are placed on the surface of an agar plate swabbed uniformly with bacteria.

Question 32

sulfonamides?

Answer 32

Inhibit folic acid synthesis

Question 33

Amongst those antibiotics that act by inhibiting protein synthesis, several members this drug class are known to produce side effects related to both drug interactions caused by inhibition of P-450 and cardiac effects (QT prolongation/Torsade de pointes). Which drug class is this?

Answer 33

Macrolides

Question 34

fluroquinolones can cause QT prolongation T/F

Answer 34

True

Question 35

Major side effects of aminoglycosides

Answer 35

Ototoxicity - both reversible auditory & irreversible vestibular toxicity due to damage of hair cells;
2) nephrotoxicity - caused by damage to the renal proximal convoluted tubule, and 3) neuromuscular blockade - more rare & most commonly seen in patients with myasthenia gravis.

Question 36

These drugs are known for their effects on bone and teeth, and for causing some degree of increased photosensitivity.

Answer 36

Tetracyclines

They are cleared by the kidney. Nephrotoxicity possible

Question 37

Antibacterials regarded as generally safe to prescribe in pregnancy.

Answer 37

Most penicillins, erythromycins and cephalosporins are not teratrogenic and are considered safe to use in pregnant patients; however, tetracyclines can cause pancreatitis and fatty necrosis of the liver in preganant individuals.