Sulfonamides, Trimethoprim, and Fluoroquinolones

Question 1

Sulfonamides

Answer 1

• Short acting: Sulfisoxazole (oral agent)
• Intermediate agting: Sulfamethoxazole
• Long acting: Sulfadoxine
  Sulfacetamide (local agent)

Question 2

Sulfonamides: Mechanism of Action

Answer 2

• Bacteriostatic inhibitors of folic acid synthesis
• Competitive inhibitors of dihydropteroate synthase (enzyme that transform p-aminobenzoic acid (PABA) to dihydrofolic acid)
• They can also act as substrate for this enzyme, resulting in the synthesis of nonfunctional forms of folic acid

Question 3

Sulfonamides: Clinical use

Answer 3

• Active against gram-positive and gram-negative organisms, Chlamydia, and Nocardia
• Simple UTI: triple sulfa, sulfisoxzole (oral)
• Ocular infections: sulfacetamide (topical)
• Burn infections: mafenide, silver sulfadiazine (topical)
• Ulcerative colitis, rheumtoid arthritis: sulfasalazine (oral)
• Toxoplasmosis: sulfadiazine + pyrimethamine + folinic acid (oral)

Question 4

Trimethoprim

Answer 4

• Inhibitor of folic acid synthesis

- Selective inhibits dihydrofolate reductase (enzyme that transform dihydrofolic acid to tetrahydrofolic acid

Question 5

Trimethoprim-sulfamethoxazole (TMP-SMX)

Answer 5

• Antimicrobial synergi causing sequential blockade of folate synthesis
• Bactericidal
• Treatment of UTI and in respiratory, ear, and sinus infections caused by H. influenza and Moraxella catarrhalis
• Used for infections due to Aeromonas hydrophila, and the drug of choice for prevention and treatment of pneumocystis pneumonia in immunocompromised patients
• Drug of choice in nocardiosis
• Backup drug for cholera, typhoid fever, and shigellosis

Question 6

Fluoroquinolones: First generation

Answer 6

• Nalidixic acid

- Norfloxacin

Question 7

Fluoroquinolones: Second generation

Answer 7

• Ciprofloxacin

- Ofloxacin

Question 8

Fluoroquinolones: Third generation

Answer 8

• Levofloxacin
• Gatifloxacin
• Sparfloxacin

Question 9

Fluoroquinolones: Fourth generation

Answer 9

• Moxifloxacin

- Trovafloxacin

Question 10

Fluoroquinolones: Mechanism of Action

Answer 10

• Bactericidal
• Exhibit postantibiotic effect
• Inhibit microbial nucleic acid metabolism
• Inhibit topoisomerase II (DNA gyrase) –> block the relaxation of supercoiled DNA that is catalyzed by DNA gyrase, a step required for normal transcription and duplication
• Inhibit topoisomerase IV that is required by bacteria for cell division

Question 11

Ciprofloxacin

Answer 11

• Alternative to third-generation cephalosporines in gonorrhea

Question 12

Ofloxacin

Answer 12

• Alternative to third-generation cephalosporines in gonorrhea
• Eradicate accompanying organisms such as Chlamydia (7-day course of treatment is required)

Question 13

Levofloxacin

Answer 13

• Activity against organisms associated with community-aquired pneumonia, including atypical such as M. pneumonia

Question 14

Sparfloxacin

Answer 14

• Activity against gram-positive organisms, including penicillin-resistant pneumococci
• Can cause prolongation of QT interval, with possible risk of cardiac arrhythmias

Question 15

Moxifloxacin, Trovafloxacin

Answer 15

• Fluoroquinolones with the wides spectrum of activity, which includes both gram-positive and gram-negative organisms and anaerobic bacteria

Question 16

Norfloxacin

Answer 16

• Activity against common pathogens that cause UTI