Page 848 - Basic _ Clinical Pharmacology ( PDFDrive )

46 Sulfonamides,
P
T
A
C
H
R
E

Trimethoprim, &

Quinolones

*
Camille E. Beauduy, PharmD, & Lisa G. Winston, MD

C ASE STUD Y

A 59-year-old woman presents to an urgent care clinic with tract infections in the past year. Each episode was uncom-
a 4-day history of frequent and painful urination. She has plicated, treated with trimethoprim-sulfamethoxazole, and
had fevers, chills, and flank pain for the past 2 days. Her promptly resolved. She also has osteoporosis for which she
physician advised her to come immediately to the clinic for takes a daily calcium supplement. The decision is made to
evaluation. In the clinic she is febrile (38.5°C [101.3°F]) treat her with oral antibiotics for a complicated urinary
but otherwise stable and states she is not experiencing any tract infection with close follow-up. Given her history,
nausea or vomiting. Her urine dipstick test is positive for what would be a reasonable empiric antibiotic choice?
leukocyte esterase. Urinalysis and urine culture are ordered. Depending on the antibiotic choice are there potential drug
Her past medical history is significant for three urinary interactions?

■ ANTIFOLATE DRUGS Mechanism of Action & Antimicrobial
Activity
SULFONAMIDES Sulfonamide-susceptible organisms, unlike mammals, cannot

use exogenous folate but must synthesize it from PABA. This
Chemistry pathway (Figure 46–2) is thus essential for production of
The basic formulas of the sulfonamides and their structural simi- purines and nucleic acid synthesis. As structural analogs of
larity to p-aminobenzoic acid (PABA) are shown in Figure 46–1. PABA, sulfonamides inhibit dihydropteroate synthase and folate
Sulfonamides with varying physical, chemical, pharmacologic, production. Sulfonamides inhibit both Gram-positive bacteria,
and antibacterial properties are produced by attaching sub- such as Staphylococcus sp and Gram-negative enteric bacteria such
stituents to the amido group ( ⎯ SO ⎯ NH ⎯ R) or the amino as Escherichia coli, Klebsiella pneumoniae, Salmonella, Shigella, and
2
group ( ⎯ NH ) of the sulfanilamide nucleus. Sulfonamides tend Enterobacter sp, as well as Nocardia sp, Chlamydia trachomatis, and
2
to be much more soluble at alkaline than at acid pH. Most can some protozoa. Rickettsiae are not inhibited by sulfonamides but
be prepared as sodium salts, which are used for intravenous are instead stimulated in their growth. Activity is poor against
administration. anaerobes. Pseudomonas aeruginosa is intrinsically resistant to
sulfonamide antibiotics.
Combination of a sulfonamide with an inhibitor of dihy-
* The authors thank Henry F. Chambers, MD and Daniel H. Deck, for drofolate reductase (trimethoprim or pyrimethamine) provides
their contributions to previous editions.
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