What Do We Really Know About Antibiotic Pharmacodynamics?

Abstract

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, beta-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.

Post-antibiotic effect of colistin, alone and in combination with amikacin, on Pseudomonas aeruginosa strains isolated from cystic fibrosis patients

“…3 Besides quantitative pharmacodynamic parameters, such as AUC 0À24 :MIC, Cmax:MIC and T4MIC, which have been proposed as likely predictors of clinical and microbiological success, PAE provides potential influence on antimicrobial dosing regimens in clinical practice, where agents inducing a long PAE may be administered with longer dosing intervals than currently employed, without loss of efficacy. 9 Our experiments showed that durations of the PAE of amikacin were significantly increased in a concentration-dependent manner. When the concentration was increased to 20Â MIC, the increase in duration of PAEs were almost 2.5 times longer than when the agent was applied at concentrations equal to 1Â MIC (Po0.001; Figure 1).…”

Analysis of pharmacokinetics and PK/PD parameter Cmax/MIC for ciprofloxacin in patients with neutropenic fever

“…W przypadku antybiotyków wykorzystanie mierzalnej wrażliwo-ści czynnika etiologicznego in vitro (MIC) oraz podstawowych parametrów farmakokinetycznych pozwala określić efekt farmakodynamiczny [2,3]. Podstawowe wskaźniki PK/PD, dobrze korelujące ze skutecznością prowadzonej antybiotykoterapii, obejmują [4][5][6][7]:…”

“…W przypadku antybiotyków wykorzystanie mierzalnej wrażliwo-ści czynnika etiologicznego in vitro (MIC) oraz podstawowych parametrów farmakokinetycznych pozwala określić efekt farmakodynamiczny [2,3]. Podstawowe wskaźniki PK/PD, dobrze korelujące ze skutecznością prowadzonej antybiotykoterapii, obejmują [4][5][6][7]:• C max /MIC -stosunek szczytowego stężenia leku uzyskanego po pojedynczej dawce (C max ) do minimalnego stężenia hamującego MIC; • AUC 24 /MIC -stosunek pola pod krzywą zależności zmian stężenia leku we krwi od czasu w ciągu 24 godz. (AUC 24 ) do MIC; • T > MIC (%) -czas, w którym stężenie leku we krwi pozostaje powyżej MIC.…”

Antibacterial activity of Ampicillin trihydrate formulated in Aluminium-Magnesium Silicate, against <i>Salmonella gallinarum</i>

“…For Ampicillin, its antibacterial activity depends on its bioavailability and on length of time it is able to maintain high concentration in blood of treated animals [6]. Differences in therapeutic actions of drugs made from same medicinal active ingredients but manufactured by different companies are reported to be due to interactions of components used in formulating the drugs and on stabilizing agents used [7].…”