Chemical stability and in vitro antimicrobial efficacy of diluted silver sulfadiazine powder and cream over a six-month period.

Abstract

BACKGROUND: Silver sulfadiazine (SSD) is commonly formulated into otic preparations to treat otitis externa, although evidence of stability and antimicrobial efficacy with long-term storage is lacking. OBJECTIVES: To evaluate the effect of storage time on chemical stability and in&#xa0;vitro antimicrobial activity of SSD diluted in sterile water, including two 1% suspensions using SSD pharmaceutical-grade powder stored at room temperature (RT) in plastic or sterile glass bottles, and a 1:9 dilution using prescription SSD 1% cream stored at RT in a sterile glass bottle. MATERIALS AND METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assessed chemical stability. Trimethoprim/sulfamethoxazole-susceptible and trimethoprim/sulfamethoxazole-resistant strains of Staphylococcus pseudintermedius (SP), meticillin-resistant (MR) SP, S.&#x2009;schleiferi (SS), MRSS, Pseudomonas aeruginosa, Proteus mirabilis and Escherichia coli evaluated by 24&#x2009;h time-kill analysis assessed in&#xa0;vitro antimicrobial efficacy. Each assessment was performed at zero, one, three and six&#x2009;months of storage. RESULTS: LC-MS/MS showed no significant change in concentration over time for any suspension. When adjusted for time and species/strain, all SSD suspensions showed significant reductions in colony forming units (cfu)/mL at 24&#x2009;h (p&#x2009;<&#x2009;0.001). Including all suspensions, a bactericidal effect (minimum 3-log cfu/mL reduction at 24&#x2009;h) occurred against 94% of total isolates, with failure against 33 of 552 isolates (6%). Bactericidal failure was more likely with the cream-based suspension (p&#x2009;<&#x2009;0.05) and at six&#x2009;months (p&#x2009;<&#x2009;0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Powder-based and cream-based SSD/sterile water suspensions showed no significant change in concentration and demonstrated in&#xa0;vitro antimicrobial activity for six&#x2009;months. Bactericidal failure was more likely with the cream-based suspension and after six&#x2009;months of storage.