Cushman Lecture 22

Question 1

Cefotetan

Answer 1

Cephamycin antibiotic
Used parenterally and has broad spectrum of activity

Releases N-methylthitetrazole which causes hypoprothrombinemia and also reacts with alcohol

Always tell patients not to drink on this antibiotic

Generally stable to beta lactamases

Question 2

Imipenem

Answer 2

Carbapenem antibiotic
Parenteral administration
Broad spectrum (Gram + and Gram -)
Used in combo with cilastatin to treat infections of the gut, GU tract, bone, skin, and ednocardium

Imipenem is the N-Formiminoyl derivative of thienamycin
inhibits Beta lactamases

It is hydrolyzed by renal dehydropeptidase-1 but can be overcome by co-administration of the dehydropeptidase-1 inhibitor cilastatin

Question 3

Aztreonam Disodium

Answer 3

Synthetic monobactam antibiotic
Parenteral agent
Focus mainly on gram - bacteria and used mainly in the treatment of severe infections especially those by penicillin resistant organisms acquired in hospitals

the oxime either makes it resistant to hydrolysis by B-Lactamases

Question 4

Vancomycin MOA and Resistance

Answer 4

Glycopeptide antibiotics
An inhibitor of Gram + cell wall biosynthesis

MOA: binds to peptidyl side chain D-ala-D-ala terminus in the peptidoglycan precursor and inhibits crosslinking to transpeptidase

Resistance: due to a mutation in the peptidoglycan cell wall precursor to D-ala-D-Lactate and the vancomycin no longer works as affinity decreases

Question 5

Vancomycin Therapeutic use and toxicity/side effects

Answer 5

Given orally to treat C. Diff
Also used to treate methicillin-resistant staphylococcus aureus (MRSA)

Toxicity/side effects: Hypersensitive response - red skin rash, Very rare but nephrotoxicity and ototoxicity

Question 6

Oritavancin

Answer 6

Lipoglycopeptide antibiotics

inhibits transpeptidation and transglycosylation
Active against a broad spectrum of gram + bacteria, including MRSA (structure is huge and could not fit in gram negative porins)
Half life is 245h ans can be used as a single dose regamin

Question 7

Telavancin

Answer 7

Lipoglycopeptide antibiotics

Similar MOA as Vancomycin. It binds to D-Ala-D-Ala terminus and blocks transpeptidation and transglycosylation

Used for treatment of MRSA and other gram+ infections

Question 8

Dalbavancin

Answer 8

Lipoglycopeptide antibiotics

Similar MOA as Vancomycin. It binds to D-Ala-D-Ala terminus and blocks transpeptidation and transglycosylation

broad spectrum of gram + bacteria including MRSA and MRSE

Half life is 204h and can be used as a single dose regimen

Question 9

Synercid

Answer 9

Streptogramin Antibiotics
Parenterally administered
Made up of 30% quinupristin and 70% Dalfopristin

Each of these compounds is bacteriostatic alone. Synercid is bacteriostatic against enterococcus faecium and bactericidal against strains of methicillin-susceptible and methicillin-resistant staphylococci

Question 10

Dalfopristin MOA

Answer 10

70% of synercid
Directly interferes with the peptidyl transferase catalyzed step

Question 11

Quinupristin MOA

Answer 11

30% of Synercid
Binds in the ribosomal tunnel and causes blockage of the tunnel

Question 12

Synercid therapeutic use

Answer 12

IV treatment for
Vancomycin resistant enterococcus faecium bacteremia
skin infections caused by MRSA
Vancomycin-resistant enteroccus faecium UTI

Question 13

Synercid resistance

Answer 13

Resistance to quinupristin is due to adenine methylation of A2058 in the 23S rRNA (does not affect dalfopristin) - Extension of the dosing to 3 times a day is well tolerated and allows fopr more sustained tissue drug level

Another possible resistance mechanism is due to efflux and enzymatic inactivation by resistant bacteria

Question 14

Synercid side effects, PK, and drug interactions

Answer 14

No significant toxicity presented by synercid

Side effects: inflammation and pain at the site of injection, nausea, diarrhea, muscle weakness and rash

PK: Half life is 1.5 hours in serum with lindear relationship between the dose and the AUC

clearance is 75% through biliary excretion and the remainder appears in the urine

Interactions: Streptogramins inhibit CYP3A4

Question 15

Linezolid MOA

Answer 15

Oxazolidinones
Given orally and IV administration
interacts with 50S subunit and prevents the formation of the 70S initiation complex (interacts specifically with 23S rNA

Question 16

Linezolid therapeutic use

Answer 16

-Vancomycin resistant enterococcus faecium
-Nosocomial pneumonia cause by Methacillin resistant strains of staphylococcus aureus
-Skin infections caused by methicillin resistant strains of staphylococcus aureus

Question 17

Linezolid Resistance

Answer 17

Target site modification - G to U substitution in the peptidyl transferase center of 23S rRNA at position 2576

Question 18

Linezolid side effects and metabolism

Answer 18

Nausea, vomiting, diarrhea, headache, tongue discoloration and oral candidiasis, thrombocytopenia, GI bleeding and anemia, neuropathy

Metabolism: Excreted in the urine as the parent drug

Question 19

Linezolid Drug interactions

Answer 19

Inhibitor of monoamine oxidase
Patients taking linezolid should not consume large quanitites of food rich in tyramine (Cheese, processed meat, wine, beans)

Question 20

Tedizolid Phosphate

Answer 20

Second generation oxazolidinone
Oral or IV administration
used for treatment of acute bacterial skin and skin structure infections
It is more potent than Linezolid vs MRSA
Prodrug that interacts with 50S subunit and inhibits the making of the 70S subunit
Activated by plasma phosphatases to create tedizolid