Trimethoprim-Sulfamethoxazole

Question 1

Structure

Answer 1

Sulfonamide antibiotics are derivatives of para-aminobezenesulfonamde

Trimethoprim is a diaminopyrimidine

Question 2

MOA

Answer 2

Sequential inhibition of microbial folic acid synthesis pathway by inhibiting bacterial dihydropteroate synthetase and dihydrofolate reductase

Bactericidal–>Time-dependent

Question 3

MOR

Answer 3

Mutation in dihydrofolate reductase or dihydropteroate synthase

Question 4

Spectrum of activity

Answer 4

Gram (+) aerobes–> MRSA, CA-MRSA

Gram (-) aerobes–> HENPEACKSSSS
- TMP-SMX is NOT active against pseudomonas aeruginosa

Pneumocystis carinii/jirovecii–> DOC

Question 5

Absorption

Answer 5

Rapidly and well absorbed after oral administration

Question 6

Distribution

Answer 6

Distributes in most tissues including the CSF in the presence of inflamed meninges

Urine, uninflamed prostatic tissue

Question 7

Elimination

Answer 7

Excreted in the urine

Dose adjustments in patients with CrCl < 30 mL/min

Question 8

Clinical uses

Answer 8

Acute, chronic, or recurrent infections of the urinary tract

Acute or chronic bacterial prostatitis

Pneumocystis carinii/jirovecii pneumonia–> DOC

Skin and soft tissue infections due to CA-MRSA

Stenotrophomonas maltophilia infections

Question 9

Adverse effects

Answer 9

Hematologic: leukopenia

Hypersensitivity reactions: rash

Others: renal insufficiency, crystalluria

Pregnancy category D–> should not be used in pregnant women or lactation due to kernicterus in the newborn due to bilirubin displacement from protein binding sites

Question 10

Drug interactions

Answer 10

Warfarin