Abstract
Objective: To determine the Minimum Inhibition Concentration of Sofinox cream, Fucidin cream, T Bact ointment against Staphylococcus aureus and to screen for the development of resistant mutants and Whole Genome Sequencing(WGS) of the strains used and the strains showing raised MIC following serial passages.
Material and Methods: An in vitro study was conducted to determine the Minimum Inhibition Concentration of Sofinox cream, Fucidin cream, T Bact ointment against seven strains of Staphylococcus aureus (ATCC 25923, ATCC 43300, ATCC 700699, 2 clinical isolates of methicillin-sensitive S. aureus (MSSA) and 2 methicillin-resistant S. aureus (MRSA). We also screened the same strains for the development of resistant mutants of Staphylococcus aureus by sub MIC exposure to Sofinox cream, Fucidin cream and T Bact ointment up to 70 serial passage and their WGS.
Results: The MIC values of the three topical antibiotics ranged between 16 µg to 64 µg for all the strains of Staphylococcal strains tested. The MIC value did not change for three strains of Staphylococcus aureus and a one-fold rise in MIC value occurred for four strains of the Staphylococcus aureus strains for Sofinox cream after 70 passages at sub MIC concentration. WGS analysis of the strains with Sofinox cream treatment, it was noted that 150 number significant genetic variations to MSSA (ATCC 25923) and 84 number for MRSA (ATCC 700699) and no significant changes with other strains.
For two of the strains the MIC value remained the same, three strains showed the one-fold rise and two strains showed a four-fold rise in MIC value for Fucidin cream after 70 passages at sub MIC concentration. Through the WGS analysis of the strains, it was noted that 185 significant genetic variations to one of the clinical isolates of MSSA followed by 102 to MRSA standard strain ATCC700699, the strains showing a one-fold rise in MIC showed 95, 85 and 76 number of genetic variations respectively.
All the strains of Staphylococcus aureus showed a rise in MIC for T Bact which ranged from one to four-fold rise. WGS analysis of the strains with T Bact ointment treatment, it was noted the variations ranging from 85 to 158 with a one-fold rise to a four-fold rise in MIC value.

Conclusions: In the present study it was observed that Sofinox cream had low resistance potential in vitro compared to Fucidin cream whereas T bact ointment had more resistance potential when exposed to sub MIC concentration of the cream/ointment. Even the WGS analysis showed variations correlating with MIC values. Hence there is a less likely chance of development of resistant mutants with the topical use of Sofinox cream even up to 8 weeks.

Key words: Minimum Inhibitory Concentration, Sofinox cream, Fucidin cream, T Bact ointment, resistant mutants