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Attending Pharmacologist in Medicine and Research Scientist Section of Clinical Pharmacology Department of Adult and Pediatric Medicine The Clinical Pharmacology Research Center Bassett Healthcare Cooperstown, New York
Published Online, January 23, 2004. www.theannals.com, DOI 10.1345/aph.1D429
Based on other details in the preface and my unfamiliarity with previous editions of this text, it appears as though this is the first edition for the current editors. The 4 editors of this edition are internationally respected in the areas of infectious diseases and antimicrobial pharmacology and were excellent choices to serve as editors for this book, which has been in print through now 8 editions since 1963. Even though the editors stated they wanted to maintain the excellence and respect that a text that has maintained itself for so many decades must have, like anyone else, given the opportunity, they obviously not only wanted to update it but also put their own imprint on it.
Although the finished product definitely meets the goal of being a user's guide based on its setup, especially throughout Section 2, there are several issues that I noted in my review of the author list, table of contents, preface, and selected chapters of each section. One of the first things that one would notice is that there appears to be an exorbitant number of chapters that have been written or cowritten by the editors. Twenty-four percent of this book is written/cowritten by the editors compared with another infectious diseases text, such as Principles & Practice of Infectious Diseases,1 with only 2% of the text written/cowritten by its editors. One wonders about the amount of bias contained in the book and its recommendations, as it is unlikely that the editors were unable to find competent authors to write the majority of chapters that the editors prepared. Evidence that the bias may be significant is contained in Chapter 47, which discusses "Infections of the Upper Respiratory Tract" (URTIs) and whose lead author is one of the editors. The chapter opens with a number of bulleted points that are supposed to be representative of the main problems associated with URTIs; however, some of the sentences come across as fairly strong conclusions that would not only apply to URTIs, but also to lower respiratory tract infections (LRTIs). The main point is that, due to resistance, macrolides are no longer considered first-line treatment options for infections caused by Streptococcus pneumoniae and Haemophilus influenzae. As these pathogens cause both URTIs and LRTIs, a reader may take these recommendations as being relevant to RTIs in general rather than to URTIs as the chapter suggests.
There are a number of reasons why macrolides may not be first-line choices for URTIs; however, resistance seems like an odd one when one considers that there is not an incidence of failures that has been reported with the macrolides due to resistance that even comes close to matching the incidence documented in vitro. The failures that have been reported for RTIs in general have been very isolated and/or collected over long periods of time and are minute when one considers the volume of these drugs used. Rather, it may easily be argued that they be reserved for RTIs in which atypical pathogens are commonly isolated, which are usually LRTIs rather than URTIs. This is because macrolides are second-line agents for the majority of infections described in this chapter, with the exception of sinusitis, in which they are used commonly as first-line or alternate first-line agents. The fact that this statement made by the editors can be extrapolated to LRTIs could be described by some as irresponsible and inappropriate.
First, like the URTIs, since no patient has a documented pathogen when
treatment is instituted, clinicians could assume that any presenting infection
may be pneumococcal as it is the most common community-acquired respiratory
pathogen in the world and avoid macrolides as first-line therapy. However, the
community-acquired pneumonia (CAP) treatment guidelines from the Infectious
Diseases Society of America, the American Thoracic Society, and the British
Thoracic Society recommend a macrolide in combination with a 
-lactam as
initial first-line empiric therapy for patients hospitalized with moderate to
severe CAP knowing full well that the infection could be pneumococcal.
In addition, numerous international papers have been published/presented, even from regions of the world that have both a high incidence of pneumococcal macrolide resistance and a high incidence of high-level resistance. These studies have documented either equal clinical outcomes in pneumococcal pneumonia when cases caused by susceptible isolates are compared with those caused by resistant isolates and/or that mortality is higher and length of stay longer if a macrolide was not a part of their treatment regimen. Based on these factors, it is important for practitioners to remember when authoring a chapter or editing a text that it is their responsibility not to put their bias into it. Rather, they are to explain and interpret the findings from the literature and update them when old theories no longer hold true. In this case, even though historically we have treated URTIs based on in vitro findings, outcomes and current treatment recommendations are in contrast to what we have thought and/or done in the past. As such, it is the mission of the editors to present this disparity and update the reader rather than reinforce recommendations that no longer hold true for at least this class of antibiotics.
Although some chapters in Section 1 were excellent, such as "Drug Interactions Involving Antimicrobial Agents," which was very complete and well laid out, others fell short either in content or accuracy. For example, the chapter "Pharmacodynamics of Anti-Infectives: Target Delineation and Target Attainment" was most likely meant to describe the various pharmacodynamic principles associated with various classes of anti-infectives. However, the reader is presented instead with an excellent, indepth review of the methods that are used in defining exposure-response (effect) relationships. As the book is a general overview of the various topics it discusses, rather than an in-depth discussion of the topics and their various nuances, this chapter should have presented a general overview and should have been titled: "Pharmacodynamics of Anti-Infectives." A general overview of how each class of antiinfectives should be dosed to optimize the clinical and microbiologic outcomes as has been defined to date would have fit the flow of the book better.
The chapter on "Antibiotics and the Immune System" discusses an important topic that should be part of any clinical text on infectious diseases; however, some of the data presented are incorrect and others have been omitted that should have been available to the authors when they were making their final changes. For example, the authors state macrolides are unable to eradicate intraphagocytic Staphylococcus aureus and that this may be due to them existing in the cytosol fraction of the cell rather than the lysosomes. In contrast to those statements, studies have been published demonstrating that macrolides are capable of eradicating intraphagocytic S. aureus. It has been known since the late 1980s that macrolides primarily reside in the lysosomes rather than the cytosol, which is where fluoroquinolones exist.
Although the book does discuss a study involving intraneutrophil pneumococci and the effects of a variety of antibiotics, the discussion is shorter than it should have been, as there are more interesting findings in the study than presented in the book. Rather, the discussion would have benefited from noting that there was increased suppression of growth as some of the antibiotics' intracellular concentrations increased, such as was seen with the macrolides. The concentrations used in that study were reflective of serum concentrations or just above serum concentrations rather than 1-2 log-fold higher concentrations that are usually found in neutrophils clinically. There was space for extrapolation of those findings by the chapter's authors as to what may happen to pneumococcal colony growth if clinically relevant concentrations beyond those measured in serum were used not just with the macrolides, but also with the fluoroquinolones and rifamycins.
The authors also omitted some important information released in 2002 by Dr. William Craig's group that demonstrated that members of a variety of classes of antibiotics were more effective in the mouse thigh infection model (pneumococcal infections) when they used immunocompetent as opposed to neutropenic mice. This, along with in vitro data, raises the question whether an additive or synergistic effect between antibiotics and the immune system exists in vivo that we have been missing in vitro. Such a highly energizing concept should have found its way into the book even if the chapter was at its galley proof stage.
The chapters found in Section 2 provide overviews of the class(es) of antimicrobials in the title of each chapter, as well as the agents in each class that are currently being used clinically. These chapters provide a nice brush-up for the average practitioner on the classes and their respective agents, but are far from being detailed about all the nuances that are encountered clinically. Nor do they provide any guide to the reader as to how to dose any of the agents that have historically needed individualized dosing. The absence of this dosing guidance is obvious in the chapter on aminoglycosides.
Other chapters have incorrect data (ie, the half-life of azithromycin is 68-72 hours, not 11-40 hours) or were written by industry people who, despite being experts in the field, have a financial stake in the perception of one or more of the drugs. This is most obvious in the macrolide chapter whose lead author is employed by Aventis, which is attempting to bring telithromycin to market. Possible evidence of bias is the fact that the monograph for telithromycin, which has yet to be launched in the majority of the world's markets, is larger than that of a drug like azithromycin that has been used extensively globally for over a decade. One may go so far as to say that the bias is also evident in the telithromycin monograph, which states that it was well tolerated during clinical trials with the main adverse event being diarrhea. As it is the tolerance (questions of QTc interval prolongation, hepatotoxicity, significant incidence of blurred vision after dose administration) and not the efficacy of telithromycin that has primarily held up its approval by the Food and Drug Administration for at least the last 2 years, as well as the potential for significant drug interactions due to CYP inhibition, the statement that it has been well tolerated appears a bit conveniently tame. The antiinfective class chapters would have also benefited from including trade names that are used in the US market rather than the foreign trade names if the text is to be marketed as an infectious diseases reference in this country.
In conclusion, it is my impression that this text provides a relatively accurate but general overview of the topics that are listed in its Table of Contents, and that it may be worth the listed cover price of $179 if that is all the reader wishes for it to provide. If the reader wants a more in-depth review of the topics in this text, they would be more likely to be satisfied with their purchase if it was the most recent edition of one of several other infectious diseases texts, such as Principles & Practice of Infectious Diseases,1 albeit most likely at a higher price.
Footnotes
By Roger G Finch MB BS FRCP FRCPath FRCPEd FFPM, David Greenwood BSc PhD DSc FRCPath, S Ragnar Norrby MD PhD FRCP(Edin), and Richard J Whitley MD. Published by Churchill Livingstone, an imprint of Elsevier Science Ltd., Philadelphia, PA, 2003. ISBN 0-443-07129-2. Clothbound, xii + 964 pp. (28.5 x 22.5 cm), $179. www.elsevierhealth.com
References
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