DNA Inhibitors

Question 1

What is the MOA of Fluoroquinolones?

Answer 1

Inhibit DNA gyrase (topoisomerase II), inhibits DNA synthesis, bactericidal dose dependent

Question 2

How does resistance for quinolones happen?

Answer 2

Alterations in DNA gyrase binding, mutation in the QRDR of DNA gyrase enzyme

Decreased accumulation of porin proteins, energy dependent efflux system

Question 3

Classify the generation and activity of fluoros?

Answer 3

1st - Nalidixic acid - Uncomplicated UTI
2nd - Cipro, Ofloxacin - Improved systemic activity, Gram - activity (P. aeruginosa with Cipro)
3rd - Levo, Gemifloxacin - Extended activity of Gram +, retains Gram - (P. aeruginosa with Levo)
4th - Moxifloxacin - Additional anaerobic activity

Question 4

What is the spectrum of Moxifloxacin?

Answer 4

Gram + organisms such as Strep. sps, S. pneumoniae, Enterococcus, S. aureus (MSSA), anaerobes, atypical bacteria

Question 5

What is the spectrum of Cipro and Levoflox?

Answer 5

Gram - organisms such as H. influenzae, Enterobacteriaceae (EPK), P. aeruginosa

Levo also does Gram + such as Strep sps, S. pnmae, Enterococcus, atypical bacteria

Question 6

What are some ADEs of quinolones?

Answer 6

Avoid in pregnancy and children, Rash/photosensitivity, Tendon rupture (incr. risk if above 60 y/o, steroids), Dysglycemia, QTc prolongation, C. diff colitis, False + opioids on urine screen, CNS/neurologic effects

Question 7

Gemifloxacin can cause what?

Answer 7

Rash/photosensitivity especially females below 40 yo

Question 8

What is the MOA of Folate antagonists?

Answer 8

Inhibit sequential steps in folate metabolism, bacteriostatic

Question 9

How does resistance happen for folate antagonists?

Answer 9

Sulfonamides: Alteration in enzyme requiring PABA, Increased inactivation of drug, Alternative metabolic pathway, Increased production of PABA

Trimethoprim: Altered DHFR (lower affinity)

Question 10

What is the drug target for Sulfonamides?

Answer 10

DHPS (dihydropteroate synthase)

Question 11

Drug target for Trimethoprim?

Answer 11

DHFR (dihydrofolate reductase)

Question 12

Spectrum for TMP/SMX?

Answer 12

Gram +: Listeria if allergic to penicillin, mild MRSA

Gram -: UTI (70% EPK), Steno malthophilia, Burkholderia sps, Pneumocystis, Toxoplasmosis, Nocardia

Question 13

What is the elimination route for TMP/SMX? Combination for TMP/SMX?

Answer 13

Renal, 1 part trimethoprim to 5 part sulfa

Question 14

Specific dosing and indications?

Answer 14

1 DS daily (SBP, PcjP prophylaxis)
1 DS Q12h (UTI, SSTI)
2 DS Q6-12h by weight (PcjP treatment)

Question 15

What are the ADEs of TMP/SMX?

Answer 15

Rash - can progress to Steven Johnson syndrome
Heme - Neutropenia, Anemia in G6PD deficiency
Renal - K+ (hyperkalemia), AIN
Neural tube defect risk
Sulfa allergy - Sulfamethoxazole, sulfadiazine, sulfisoxazole, sulfacetamide

Question 16

Drug interactions with TMP/SMX?

Answer 16

Warfarin - SMX inhibits CYP 2C9

Phenytoin, oral hypoglycemics

Question 17

What is Dapsone used for?

Answer 17

Mycobacterium leprae, causes hemolytic anemia, CI in patients deficient in G6PD

Question 18

What is Sulfadiazine with Pyrimethamine used for?

Answer 18

Toxoplasmosis treatment

Question 19

What is fosfomycin tromethamine?

Answer 19

Phosphonic antibiotic, inhibits bacterial cell wall synthesis (bactericidal), inhibits PEP transferase blocking formation of cell wall precursors

Question 20

Which drug acts before beta lactams or vancomycin?

Answer 20

Fosfomycin tromethamine

Question 21

Fosfomycin is helpful for?

Answer 21

Active and clinically useful for UTI and prostatitis caused by enterococcus (including vancomycin resistant strains), enterobacteriaceae (ESBL strains)

Question 22

What is the MOA of Nitrofurantoin?

Answer 22

Nitroaromatic antibacterial, inhibits DNA and RNA functions through unclear mechanism

Question 23

Is nitrofurantoin bactericidal or static?

Answer 23

Bactericidal in urine

Question 24

What is the activity for nitrofurantoin?

Answer 24

Active against strep and staphylococcus, Enterococcus including VRE, E. coli, Klebsiella, Enterobacter (including ESBLS)

Question 25

How is nitrofurantoin absorbed and eliminated?

Answer 25

Orally, no IV formulation, achieves therapeutic concentrations in bladder
Eliminated rapidly by kidney (20 min half life)

Question 26

What are the two nitrofurantoin drugs and what are they used for?

Answer 26

Macrodantin, Macrobid (ER)

Used for prevention and treatment of UTIs

Question 27

What are the ADEs of nitrofurantoin?

Answer 27

Pulmonary (hypersensitivity, interstitial pneumonitis, pulmonary fibrosis), hepatic necrosis, peripheral neuropathy, hematologic (agranulocytosis, anemia)
CI in renal impairment (<30 CrCl)