What Do We Really Know About Antibiotic Pharmacodynamics?
What Do We Really Know About Antibiotic Pharmacodynamics?
Antibiotic pharmacodynamics is an evolving science that focuses on the relationship between drug concentration and pharmacologic effect, which is an antibiotic-induced bacterial death that also can manifest as an adverse drug reaction. The pharmacologic action of antibiotics usually can be described as concentration dependent or independent, although such classifications are highly reliant on the specific antibiotic and bacterial pathogen being studied. Quantitative pharmacodynamic parameters, such as ratio of the area under the concentration-time curve during a 24-hour dosing period to minimum inhibitory concentration (AUC0-24:MIC), ratio of maximum serum antibiotic concentration to MIC (Cmax:MIC), and duration of time that antibiotic concentrations exceed MIC (T>MIC), have been proposed as likely predictors of clinical and microbiologic success or failure for different pairings of antibiotic and bacteria. Thus far, most pharmacodynamic data reported have focused on fluoroquinolones, but work has been conducted on vancomycin, ß-lactams, macrolides, aminoglycosides, and other antibiotics. Despite the development of a number of different pharmacodynamic modeling systems, remarkable agreement exists between in vitro, animal, and limited human data. Although still somewhat premature and requiring additional clinical validation, antibiotic pharmacodynamics will likely advance on four fronts: the science should prove to be extremely useful and represent a cost-effective and efficient method to help develop new antibiotics; formulary committees will likely use pharmacodynamic parameters to assist in differentiating antibiotics of the same chemical class in making antibiotic formulary selections; pharmacodynamic principles will likely be used to design optimal antibiotic strategies for patients with severe infections; and limited data to date suggest that the application of pharmacodynamic concepts may limit or prevent the development of antibiotic resistance. The study of antibiotic pharmacodynamics appears to hold great promise and will likely become a routine part of our daily clinical practices.
Overall, the antibiotic prescribing process has been extremely subjective and has promoted a naïve understanding of how to optimize antibiotic performance. During the past 30 years, clinicians have become very familiar with the science of pharmacokinetics, which is a very useful tool for describing how drugs behave in the human host, but it does not promote an understanding of a drug's desired or undesired pharmacologic effects. Pharmacodynamics has the potential to provide clinicians with the missing tools required to make antibiotic prescribing more objective and to expand our understanding of the interaction between bacteria and antibiotics.
During the past 10 years, investigators have been able to identify possible pharmacodynamic outcome predictors and assign quantitative values that predict the success or failure of antibiotic regimens. In addition, pharmaco-dynamics offers a way to expedite the antibiotic development process and provide an additional dimension for distinguishing various members of a particular antibiotic class.
Antibiotic pharmacodynamics is an evolving science that focuses on the relationship between drug concentration and pharmacologic effect, which is an antibiotic-induced bacterial death that also can manifest as an adverse drug reaction. The pharmacologic action of antibiotics usually can be described as concentration dependent or independent, although such classifications are highly reliant on the specific antibiotic and bacterial pathogen being studied. Quantitative pharmacodynamic parameters, such as ratio of the area under the concentration-time curve during a 24-hour dosing period to minimum inhibitory concentration (AUC0-24:MIC), ratio of maximum serum antibiotic concentration to MIC (Cmax:MIC), and duration of time that antibiotic concentrations exceed MIC (T>MIC), have been proposed as likely predictors of clinical and microbiologic success or failure for different pairings of antibiotic and bacteria. Thus far, most pharmacodynamic data reported have focused on fluoroquinolones, but work has been conducted on vancomycin, ß-lactams, macrolides, aminoglycosides, and other antibiotics. Despite the development of a number of different pharmacodynamic modeling systems, remarkable agreement exists between in vitro, animal, and limited human data. Although still somewhat premature and requiring additional clinical validation, antibiotic pharmacodynamics will likely advance on four fronts: the science should prove to be extremely useful and represent a cost-effective and efficient method to help develop new antibiotics; formulary committees will likely use pharmacodynamic parameters to assist in differentiating antibiotics of the same chemical class in making antibiotic formulary selections; pharmacodynamic principles will likely be used to design optimal antibiotic strategies for patients with severe infections; and limited data to date suggest that the application of pharmacodynamic concepts may limit or prevent the development of antibiotic resistance. The study of antibiotic pharmacodynamics appears to hold great promise and will likely become a routine part of our daily clinical practices.
Overall, the antibiotic prescribing process has been extremely subjective and has promoted a naïve understanding of how to optimize antibiotic performance. During the past 30 years, clinicians have become very familiar with the science of pharmacokinetics, which is a very useful tool for describing how drugs behave in the human host, but it does not promote an understanding of a drug's desired or undesired pharmacologic effects. Pharmacodynamics has the potential to provide clinicians with the missing tools required to make antibiotic prescribing more objective and to expand our understanding of the interaction between bacteria and antibiotics.
During the past 10 years, investigators have been able to identify possible pharmacodynamic outcome predictors and assign quantitative values that predict the success or failure of antibiotic regimens. In addition, pharmaco-dynamics offers a way to expedite the antibiotic development process and provide an additional dimension for distinguishing various members of a particular antibiotic class.
