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Abstract

Bactericidal testing methods occasionally are used because of the awareness of the need for lethal antimicrobial activity to treat certain deep-seated infections, e.g., bacterial endocarditis. There also is an increased awareness of the need to consider the pharmacodynamics and pharmacokinetic principles of antimicrobial therapy. This often can be achieved by assessing both results of standardized susceptibility testing and of antimicrobial assays. The serum bactericidal test represents an alternative in vitro test that incorporates pharmacodynamics and pharmacokinetic principles. The test takes into consideration the susceptibility of the pathogen; measures the combined effect of absorption and elimination of the antibiotic; the binding of the drug to serum proteins; and the effect of the parent compound as well as any metabolites against the infecting organism. This assay also measures the effect of drug interactions. This includes both the synergistic or antagonistic effects of antibiotic combinations and the interactions of other drugs with antibiotics. Finally, the serum bactericidal test, by measuring the magnitude of antibiotic concentration relative to the MBC, allows a prediction of the aggregate time of bactericidal activity. Peak serum bactericidal titers of > 8, for example, assure measurable bactericidal activity in the serum for at least three half-lives of the drug being tested. Despite all of these potential advantages, the serum bactericidal test rarely is needed. Although the test provides another predictive estimate of bacterial eradication, clinical cure depends largely upon host factors and other factors, e.g., postantibiotic effect and the growth-inhibitory effects of sub-MIC concentrations of antibiotics. When needed, however, established, reproducible methods should be available to the clinical, reference, and/or research laboratory.