Antimicrobial synergy testing based on antibiotic levels, minimal bactericidal concentration, and serum bactericidal...

Area of Science:

• Pharmacology
• Infectious Diseases
• Clinical Microbiology

Background:

• In vitro methods for assessing antimicrobial therapy often use arbitrary drug concentrations that do not reflect actual patient drug levels.
• The ratio of antimicrobial agent concentrations during therapy can differ significantly from those used in standard in vitro testing.
• Previous research suggests serum bactericidal titer (SBT) using pooled normal human serum approximates in vivo drug effectiveness.

Purpose of the Study:

• To evaluate an alternative method for assessing antimicrobial interactions using patient serum.
• To compare the predictive accuracy of a serum dilution synergy method with traditional in vitro techniques (checkerboard and kill curve).
• To determine if patient serum accurately reflects in vivo antibiotic levels for predicting antimicrobial interactions.

Main Methods:

• Determined serum bactericidal titers (SBT) and drug levels from peak and trough serum specimens.
• Analyzed samples from ten patients undergoing multiple antimicrobial therapy for endocarditis or osteomyelitis.
• Compared results from the serum dilution synergy method with checkerboard and kill curve assays.

Main Results:

• The serum dilution synergy method predicted additive interactions more frequently than checkerboard and kill curve methods.
• The serum method predicted synergy less often than the kill curve method.
• The checkerboard method predicted antagonism more often and yielded equivocal results in 40% of cases.

Conclusions:

• A serum-based method may offer a more accurate assessment of antimicrobial interactions by utilizing actual in vivo drug levels.
• This approach provides an alternative to in vitro tests that rely on arbitrary drug concentrations.
• Further investigation is warranted to validate this patient serum-based method for clinical application.