Sulfonamides & Misc Abx

Question 1

Sulfonamide Drugs

Answer 1

Sulfamethoxazole+Trimethoprim, Co-trimoxazole, TMP-SMX (Bactrim) - oral and parenteral
Sulfamethoxazole - oral
Sulfasalazine - oral
Silver Sulfadiazine - topical

Question 2

DOC for UTI

Answer 2

Bactrim - slow excretion and high urine concentration

Question 3

Sulfasalazine Use

Answer 3

Ulcerative Colitis (GI action)

Question 4

Silver Sulfadiazine Use

Answer 4

Burns - topical application

Question 5

Sulfonamide MOA

Answer 5

Antimetabolite, competes with para-aminobenzoic acid (PABA) for incorporation into folic acid:
PREVENTS FOLIC ACID SYNTHESIS
Bacteriostatic, but becomes cidal in the urinary tract

Question 6

TMP-SMX MOA

Answer 6

SULFAMETHOXAZOLE inhibits folic acid synthesis
TRIMETHOPRIM prevents reduction of dihydrofolate to tetrahydrofolate essential for one carbon transfer
This is a SYNERGISTIC relationship when coadministered as in Bactrim

Question 7

Sulfonamide Resistance

Answer 7

Increased production of an essential metabolite or drug antagonist (PABA)
Efflux pumps
Decreased permeability
Alternative metabolic pathway for synthesis of essential metabolite (plasmid)

Question 8

Sulfonamide Spectrum

Answer 8

G+ and G- (generally static unless in the urinary tract)

Question 9

Sulfonamide Uses

Answer 9

UTI (first attacks) - DOC is Co-trimoxazole (Bactrim)
Chlamydia (second line) - DOC is azythro or tetracycline
Moraxella, E. Coli, Klebsiella, Proteus, Salmonella, Vibrio sp, Burkholderia, Nocardia

Question 10

Bactrim Administration

Answer 10

Oral - absorption is adequately rapid

Cotrimoxazole is available IV, but is RARELY used!

Question 11

Sulfa metabolism

Answer 11

Liver primarily as acetylated products and excreted through the kidney.
Urine concentration is 10-20x that of plasma

Question 12

Sulfa contraindications

Answer 12

Near term pregnancies (crosses placenta and bbb)
Nursing mothers (excreted in breast milk)
Premature or jaundiced infants (immature liver)
Infants <2 months (displaces bilirubin)

Question 13

Sulfa Toxicities

Answer 13

Aplastic anemia (G6PD deficient - avoid at end of preggo)
Photosensitivity
Hypersensitivity (2nd to PCNs)
SJS and TEN
Kidney and Liver damage, microscopic hematuria
Peripheral nerve damage
KERNICTERUS (bilirubin displacement)

Question 14

Daptomycin MOA

Answer 14

Binds bacterial membranes and causes rapid depolarization of membrane potential.
Bactericidal against G+ bacteria (MRSA, MSSA) - concentration dependent

Question 15

Daptomycin Spectrim

Answer 15

Aerobic and Anaerobic G+ bacteria

Question 16

Daptomycin Resistance

Answer 16

Exceedingly rare, but does exist. Unsure mechanism

Question 17

Daptomycin administration

Answer 17

IV

Question 18

Daptomycin Metabolism

Answer 18

Half life is 8-9 hrs: once daily dosing

Excreted unchanged by the kidneys

Question 19

Daptomycin Use

Answer 19

Suitable for EMPIRIC therapy in patients with SERIOUS G+ infections; alternate to Vancomycin
Very little is known about this drug!

Question 20

Mupirocin MOA

Answer 20

Binds bacterial isoleucyl-tRNA synthetase - every isoleucine that needs to be added, can’t! Protein and RNA synthesis are inhibited.
Bacteriostatic at LOW concentrations
Bacteriocidal at HIGH concentrations

Question 21

Mupirocin Spectrum

Answer 21

Good against G+ and some G-

Question 22

Mupirocin Administration

Answer 22

Topical (to skin or nares)

Question 23

Mupirocin Use

Answer 23

Impetigo (DOC) caused by S. aureus

Intranasal application of carriers of MRSA

Question 24

Mupirocin cross-resistance

Answer 24

Practically none b/c of its unique MOA

Question 25

Polypeptide Antibiotics

Answer 25

Polymyxin B | Colistin

Question 26

Polypeptide Spectrum

Answer 26

Mostly G- infections. No effect in G+ (lack endotoxin which is the binding site)

Question 27

Polymyxin B MOA

Answer 27

Binds to G- bacterial cell membrane phospholipids (lipid A of endotoxin), increasing permeability of the cell membrane. Bactericidal against most G- bacilli, except PROTEUS and NEISSERIA

Question 28

Polypeptide Administration

Answer 28

Topical - NO GI absorption (can't be oral) | Binds well to plasma proteins (distribution after parenteral use is poor)

Question 29

Polypeptide Metabolism

Answer 29

Slow excretion through the kidney (can cause nephrotoxicity especially if not topical)

Question 30

Polypeptide Toxicity

Answer 30

NEPHROTOXICITY - use topically Paresthesia, ataxia, dizziness Visual/speech disturbances, leukopenia, granulocytopenia

Question 31

Polypeptide Use

Answer 31

Topical in combination with neomycin and bacitracin. | Topical application to wounds, burns, and the eye (pseudomonas infections).

Question 32

Neosporin Abx

Answer 32

Bacitracin (G+) Neomycin (G-) Polymyxin B (G-)