Antimicrobial Pharmacodynamics in Theory and Clinical Practice

The second edition of Antimicrobial Pharmacodynamics in Theory and Clinical Practice has expanded information on malaria, antivirals, and other newer drug classes as compared with the previous edition. As the title implies, the text thoroughly describes numerous pharmacodynamic principles but also contains informative pharmacokinetic information. This makes the chapter titles somewhat misleading, since some include the pharmacodynamic/pharmacokinetic phrasing in their titles when essentially all the chapters contain information relative to both principles. While the chapter titles are inconsistent, the section titles are distinct. In general, the chapters are independent of each other and if read successively will regress at times, with redundant explanations of these principles. The authors appear to be from varied backgrounds, and while affiliations are included, credentials are not, which can alter the perception of the information presented.

The text starts with a comprehensive introduction on the application of pharmacodynamic and pharmacokinetic data and the relation to antimicrobials. Even a discussion of more recent principles related to antimicrobials such as area under the curve/MIC (minimum inhibitory concentration), peak/MIC, and time above MIC are included. The authors go on to offer a thorough review of break points, Monte Carlo simulations, and the Clinical and Laboratory Standards Institute as compared to the European Committee on Antimicrobial Susceptibility Testing. The reviews of pharmacokinetic simulations, which include many equations, may be of limited clinical usefulness, perhaps due to the lack of clinical examples/relevance.

Chapter 4 provides a careful overview of the use of animal models of infection to elucidate the pharmacodynamic properties of antimicrobials. It describes the usefulness of these infection models, which are often used to more accurately quantify the insight gained from in vitro studies. It also describes some of the shortcomings seen when attempting to extrapolate these animal data to humans. Current information on the use of laboratory methods to assess the efficacy of combinations of antimicrobials is included in the subsequent chapter. The authors discuss some of the lack of standardization in methods used in various tests (checkerboards, time-kill curves, and diffusion models) and thereby illuminate the difficulties in extrapolation to the bedside. This chapter provides a pragmatic discussion of the differences in these models and their advantages and disadvantages in predicting the likelihood of synergism, additiveness, or antagonism during combination treatment in humans.

Section 3 begins the class-specific reviews, starting with a review of β-lactam pharmacodynamics by authors from Japan, hence the referral to various medications not available, or used clinically, in the United States. In addition, some information appears to be outdated due to statements such as third-generation cephalosporins have “become available” or “there is no oral cephalosporin that can be used to treat severe infections.” In addition, this chapter contains numerous grammatical and typographical errors, making it difficult to read. Subsequent chapters review aminoglycosides (includes dosing nomograms), quinolones, and glycopeptides (of which vancomycin has been the sole representative for more than 50 years). While the latter chapter contains useful information on vancomycin dosing, appropriate use, and recent controversies surrounding monitoring, some of the information on Clinical and Laboratory Standards Institute break points is out of date.¹ Additional chapters on macrolides and relatives, streptogramins and oxazolidinones, and tetracyclines finish out the coverage of the antibacterial agents. These last 3 chapters are generally quite good, but because of less pharmacodynamic data, they focus more on agent pharmacokinetics and provide a review of general clinical efficacy.

Section 4 begins with a chapter on the clinical pharmacology of nucleoside reverse transcriptase inhibitors, with adequate coverage of their development and pharmacokinetic characteristics. The subsequent chapter provides a general overview of pharmacodynamic variables of antivirals, with coverage of in vitro simulations and use of Monte Carlo simulations to assess the impact of these on mammalian systems.

Three chapters follow in section 5 on the antifungal agents, one of which is entitled glucan synthase inhibitors, meaning the more commonly referred to class of echinocandins. These are succinct reviews of available medications, which is challenging when new medications are being continually developed. For example, amphotericin is mentioned as the drug of choice for the treatment of Aspergillus sp, whereas newer guidelines recommend voriconazole.²

Section 6 contains one chapter on the antimalarial drugs, providing a succinct review of the pharmacokinetics and mechanism of many of the available agents. Pharmacodynamic data are limited with most of these agents; thus, this portion of the chapter is appropriately brief.

Subsequent sections include chapters on determining pharmacodynamic data from clinical research trials, applications of pharmacodynamics/pharmacokinetics in drug development, modeling of antibiotic toxicities, and pharmacodynamics and antibiotic resistance. These each provide a review of the importance of pharmacodynamics/pharmacokinetics to the future of new drug development as well as the important role this area of investigation has in understanding antibiotic action and the ways available to improve the outcomes of patients and reduce the development of resistance through greater understanding of the host-organism-drug interaction. The final section is a single chapter presenting a short primer on pharmacoeconomics methodology.

While this text may serve as a useful reference for antimicrobial/infectious disease researchers or those involved in antimicrobial drug development or clinical trials, it may not be helpful for the general practitioner.