Why does combining a sulfonamide (enzyme A inhibitor) with trimethoprim (enzyme B inhibitor) reduce the probability that a bacterial population will develop clinically important resistance compared to monotherapy?

• A. Because the two drugs chemically react with each other to form a new compound that irreversibly modifies bacterial DNA, making resistance mechanically impossible.
• B. Because resistance would require simultaneous independent mutations or mechanisms conferring resistance to both drugs; inhibition at two sequential steps makes escape via a single mutation unlikely.
• C. Because host immune responses are suppressed differentially by each drug, and suppression of immunity is what prevents the emergence of resistant bacterial clones during therapy.
• D. Because combining two inhibitors increases the metabolic rate of the pathway so bacteria exhaust their substrates more quickly, preventing resistant mutants from growing.

Answer: (B)