The same anti-infective solutions were compared by MIC values in Table IV. The MIC values represent the bacteriostatic effect of each solution expressed as the percent of product required to inhibit growth; the lower the MIC, the more the test solution can be diluted and still inhibit microbial proliferation. Sulfacetamide solutions preserved with thimerosal have MIC values ranging from 0.2 to 2.8 for the five test microorganisms. The solutions preserved with parabens exhibit slightly higher MIC values for Pseudomonas, Serratia, and spores of Aspergillus (1.5-6.5) and significantly higher MIC values for Staphylococcus and Candida (19.6 and 5.0, respectively).
The effect of steroids and EDTA on the antimicrobial efficacy of the solutions was evaluated using the kill rate and MIC methods. The kill rates appear to be unaffected by the presence of steroids (Table V). The MIC values agree with this observation (Table VI). However, the addition of 0.1% EDTA to the sulfacetamide solutions significantly reduced the D-value for Pseudomonas, Serratia, and Candida regardless of the preservative (Table VII). This increase in antimicrobial activity, as indicated by smaller D-values, is not reflected by significantly different MIC values (Table VIII).
Discussion
The results of both kill rate and MIC methods used to evaluate ophthalmic anti-infective solutions provide a better understanding of the antimicrobial effects of sulfacetamide and the clinical use of products containing this drug. Both methods indicate greater antimicrobial activity when thimerosal is used as the solution preservative than that seen with parabens: the kill rate for Serratia is increased and the MIC values for Staphylococcus, Candida, and possibly Aspergillus are decreased. The results using both methods also indicate that the addition of steroids to sulfacetamide formulations does not affect kill rates or MIC values.
However, only one method could detect the effect of EDTA on the antimicrobial activity of sulfacetamide. The kill rate for Pseudomonas, Serratia, and possibly Candida increased with the addition of EDTA, yet no differences in MIC values were observed. Thus, evaluation of antimicrobial activity using just one technique may not be adequate in determining the efficacy of ocular anti-infective products. MIC values are routinely used to evaluate the microbial sensitivity of parenterally administered antibiotics, yet this method of evaluation may miss interactions of other agents important in ocular therapy. This study shows that sulfacetamide solutions containing EDTA and thimerosal as preservatives are more effective against the organisms tested than sulfacetamide solutions containing paraben preservatives without EDTA. The antipseudomonal activity of thimerosal-preserved sulfacetamide solutions is particularly interesting, since they are usually not considered effective against this microorganism.