A clinical isolate has MIC and MBC determined as follows: MIC = 1 µg/mL; MBC = 32 µg/mL. Another antibiotic shows MIC = 4 µg/mL; MBC = 8 µg/mL. For a severe infection in a patient where bactericidal therapy is preferred, how should these data influence antibiotic selection if achievable serum concentrations for agent A top out at 4 µg/mL and for agent B at 16 µg/mL?

• A. Neither agent can be used because both have MBC values inconsistent with MIC breakpoints; therapy should be withheld until a new antibiotic with equal MIC and MBC values is available in the formulary.
• B. Agent A is preferable because its lower MIC (1 µg/mL) guarantees better clinical success even though its MBC is high; MIC is always the primary determinant and MBC can be ignored in severe infections if MIC is low.
• C. Choose agent A at the highest tolerated dose because lower MICs reduce resistance development, and achieving sub-MBC exposures is desirable to limit selective pressure and thus is preferable for long-term stewardship despite immediate clinical needs.
• D. Agent B (MIC 4 µg/mL, MBC 8 µg/mL) is preferable because its MBC (8 µg/mL) is below the achievable serum peak of 16 µg/mL so bactericidal concentrations are attainable; agent A cannot reach its MBC (32 µg/mL) at achievable serum levels and thus is unlikely to be bactericidal in vivo despite a lower MIC.

Answer: (D)