a $ulfonamlde-realstant organisms have been reported as a Despite several reports of in vitro assays of the antifrequent consequence of the clinical use of sulfaelazine silver, microbial activity of sulfadiazine silver, the specific role of At this bum center, sultfnmide resistance occurred in more sulfadiazine in the antibacterial activity of this salt has not than 80% of gram-negative Isolates. We tested the requirement been defined.' The question of whether sulfadiazine plays a for the Individual antimicrobial activities of sulfadlatine and direct antibacterial role as a sulfonamide, behaves as a sllver tor In vitro activity of sulfsdiazine sliver. The sulfadlazine chemical coordinator of silver ion, or has both functions in component Is not necessary for In vitro sensitivity. In vitro sensitivity to sulfadlazlne sliver does not consistently predict vitro has not been answered. We have used a bacteriologthe presence of therapeutic activity In Pseudomonas aeruglnically inactive analogue of sulfadiazine, 2-benzenesulosa-inected rats with burns. We describe an example of a fonamidopyrimidine (ISR-44), as a control molecule to test tranoferable multiple-antiblotic resistance plasmid that con-the specific silver and sulfonamide activities of sulfadiazine tains selectable sulfonamide resistance. The use of sulftdla-silver in vitro.' The analogue ISR-44 has been shown to have zine slilver cn, therefore, lead to the selection of organisms silver-coordinating properties similar to sulfadiazine.' that are resistant not only to sulfonamides but to antiblotlcs of Sulfadiazine and ISR-44 were examined in vitro as both clinical consequence, and this possible risk must be considsodium and silver salts and also in vivo, using rats with swed in electing to use the agent.burns that were infected with sulfonamide-sensitive and a (Arch Surg 1983;118:161-166) sulfonamide-resistant strain of Pseudomonas aeruginosa.We report our findings, define the sulfonamide requirehe silver salt of sulfadiazine is the chemotherapeutic ment for in vitro activity of sulfadiazine silver, and address T agent most commonly used in the topical treatment of the significance of in vitro sensitivity to sulfadiazine silver hospitalized patients with burns. Shortly after first using in therapeutic activity against experimental P aeruginosa this agent, Lowbury et al' observed increased sulfonamide burn wound sepsis. Additionally, we present an example of resistance among gram-negative organisms isolated from the potential risk inherent in maintaining sulfonamide burns. We have noted a similar phenomenon. At our burn resistant plasmids in the clinical burn environment. center, sulfadiazine (in sulfadiazine silver salt) is the only bacteriologically active para-aminobenzoic acid antagonist MATERIALS AND METHODS iThe analogue ISR-44 was synthesized by condensation in pyridine of benzene sulfonyl chloride and 2-aminopyrimidine. The

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