There's indeed chemical cross-reactivity between sulfonamide antimicrobials and diuretics (furosemide, HCTZ and acetazolamide), but it's generally not clinically important. Most people who've previously reacted to sulfonamide antimicrobials, including the patients you describe, are able to tolerate these diuretics. This may be because the sensitivity is dose-related and they only react with very high doses of the cross-reacting medication, or they've lost their sensitivity, or their initial reaction wasn't due to the sulfa, but to the underlying infection. Patients with sulfonamide sensitivity can often be "desensitized," by starting at a very low dose and gradually raising it over a 10- to 30-day period. If they've shown that they can tolerate a sulfonamide, they should continue on it. If the dose needs to be increased, it's a good idea to do it slowly, to cut the risk of triggering a reaction. PK