Class
Drug
Trimethoprim/Sulfamethoxazole
MOA
–Blocks folic acid synthesis
-SMX: sel toxic to bacteria
b/c mammalian cells lack
dihydropteroate synthetase
Spectrum
Flurinated
quinolones
Blocks the uncoiling of
DNA by preventing the
action of topoisomerase
II and IV (DNA gyrase)
- CIDAL
Blks topoisomerase II &
IV
Damage DNA, bacteria
convert to highly
reactive intermediates
Converted to
formaldehyde &
ammonia in ACID
environment only
-cidal G- UTI
Urinary tract
antiseptics
Ciprofloxacin
Norfloxacin
Nalidixic acid
Nitrofurantoin
Methenamine
Resistance
Dist/Elim
-Staic & cidal
G-/+
Broad
spectrum
Mutation of
binding site
on
topoisomerase
-pseudomonas
-cidal
limited
Conc in the urine
Conc in the urine,
contraindicated
w/renal failure
Everywhere, but only
converted in acid
environ. (urine!)
1. Summary
a. Multiple drug treatments for urinary infections
i. Empirical treatment typically involves Fluoroquinolone (Ciprofloxacin),
Trimthoprim/Sulfamethoxazole and/or Nitrofurantoin
ii. Drugs that are not excreted in their active form in urine are erythromycin,
Chloramphenicol, Rifampin
iii. Drugs with known toxicity in pregnancy are tetracyclines (brown teeth)
and sulfa drugs
1. Suspect that there is toxicity (from animal studies) for
trimethoprim, clarithromycin, ciprofloxacin, fluconazole,
miconazole, terconazole, isoniazid, rifampin and mebendazole
2. No known toxicity (in pregnancy) for amoxicillin, ampicillin,
dicloxicillin, nitrofurantoin, metronidazole, Cephalosporins,
clindamycin, erythromycin, azithromycin, famciclovir, acyclovir,
clotrimazole
3. No fetal harm from Nystatin
b. Emphasize mechanism of action for:
i. nitrofurantoin –
1. damage to DNA by reactive metabolites
2. Secreted into renal tubules to have a selective urinary antiseptic
effect
ii. Nalidixic Acid
1. Quinoloine affecting DNA gyrase
2. Similar concentration mechanism
iii. Methenamine
1. Generates formaldehyde in an acidic environment
c. Know that dose adjustments relate to creatinine clearance if drug is cleared by
kidney and the effect of age on creatinine clearance
d. Know generalities about time- and concentration-dependent killing
Practice Questions:
1.
2.
3.
The key concept behind the effectiveness of urinary tract antiseptics is_____________.
If a patient as decreased renal function, should you change antibiotic dosing? What are your
options for dosing changes?
Match the UTI antibiotic with the mechanism of action:
A. Trimeth/Sulfmeth.
B. Ciprofloxacin
C. Nalidixic acid
D. Nitrofurantoin
E. Methenamine
MOA:
1. blocks topoisomerase II & IV (2 drugs)
2. blocks folate metabolism
3. converted to formaldehyde & ammonia in acidic environment
4. damages DNA, bacteria convert it to highly reactive intermediates
4. Patient present in clinic with UTI. Empirically, what three drug classes could you use to treat the
patient?
5. A pregnant patient presents in clinic with a UTI. What drug/drug classes would you avoid using
because they are Class D teratogens (2)? What teratogenic classes do the other options belong to?
A. Nystatin
B. tetracyclines
C. sulfa drugs
D. nitrofurantoin
E. ciprofloxacin
Answers:
1. they are concentrated in the urine.
2. Yes, either reduce dose or change time interval between dosing.
3. A, 2; B, 1, C, 1; D, 4; E, 3
4. T/S, fluorinated quinolones, urinary tract antiseptics.
5. Class D = B &C, A, Nystatin is class A (not harmful); D, nitrofurantoin is class B; E,
Ciprofloxacin is class C.