Fungi are common causes of clinical illness and, in at-risk individuals, this can lead to significant morbidity and mortality. While fungal diseases in otherwise immunocompetent individuals are mainly localized, it may become ‘opportunistic’ and invade tissues and disseminate or embolize to distant sites in immune-compromised populations. Indeed, there has been an emergence of various fungal diseases in recent decades, and this has understandably paralleled the rise in the number of individuals whose immune function is markedly impaired by immunosuppressive drugs, cytotoxic chemotherapeutic agents, biological therapies or HIV infection. In addition, medical practice continues to advance with the introduction of devices that improve quality of life (e.g., joint prosthesis) and prolong survival (e.g., cardiac devices), which also creates unique patient populations predisposed to these ‘opportunistic’ fungal infections.
With the increased appreciation of the role of fungi in human illness, there has been renewed interest in the clinical development of newer antifungal drugs that have now expanded the previously limited armamentarium for the treatment of these infectious diseases. To provide a comprehensive yet insightful examination of the current state of antifungal therapy in modern medicine, the textbook Antifungal Therapy was developed, with the practicing clinician as the major target for readership. World-renowned editors Mahmoud A Ghannoum and John Perfect assembled a cadre of established and rising mycology experts to review and discuss the epidemiology, pathogenesis, diagnostics, prevention and treatment of fungal infections in humans. It is noteworthy that the majority of contributing authors are colleagues of the two editors in their respective institutions, although a few experts were also recruited from other centers, including those from international locations in China, Japan, Lebanon and Turkey. All the authors involved have done a great job in discussing the various aspects of clinical mycology.
While Antifungal Therapy is divided into four different sections, it is evident that each of the sections cannot be considered independent of the others. Section one, which is a collection of nine chapters discussing the general issues with antifungal therapy, commences with a brief history of antifungal drug development. This chapter provides a succinct narrative of the evolution of antifungal drug therapies from the use of potassium iodide and griseofulvin for cutaneous fungal infections, to the rise of polyenes as a standard antifungal drug for several decades, to the introduction of the azoles, and later, the echinocandins. Some drugs that failed in clinical development, such as systemic nystatin and its liposomal formulation, are also briefly highlighted in this chapter. Perhaps one of the strongest chapters in the first section is the ‘Epidemiology of Fungal Infections’ chapter; I am particularly impressed by the comprehensive nature of this chapter, which serves as an excellent foundation for understanding the management issues in subsequent chapters.
The textbook is limited by the lack of a comprehensive chapter that deals with the pathogenesis of fungal infections, although three independent chapters in this first section attempted to discuss this. At first glance, I expected to read about various mechanisms of how fungi invade tissues in the chapter ‘Experimental Animal Models of Invasive Fungal Infections,’ but soon discovered that this chapter was devoted mainly to the discussion of animal models of antifungal drug discovery and preclinical testing. Subsequent editions of this book should include a chapter dealing with fungal disease pathogenesis, as this may provide insight into potential novel avenues for antifungal therapy. At the cutting edge of clinical mycology is the chapter devoted to ‘Fungal Biofilms and Catheter-Associated Infections,’ which is important in understanding the pathogenesis of fungal persistence, antifungal resistance and clinical failures. While the chapter succeeded in providing a very detailed discussion on experimental models of biofilm-related infection, it was lacking in its clinical translation (and as I perused the subsequent chapters of this book, I was surprised that there was no chapter devoted to the clinical management of device-associated fungal infection in section four, and I suggest the addition of this chapter in future editions of this textbook). The chapter on the host–fungi relationship (‘The Immune Response to Fungal Challenge’) attempted to discuss the role of innate and adaptive immunity in the control of fungal infections, although the inclusion of molecules that are not yet associated with fungal disease pathogenesis (such as Toll-like receptors 3 and 7, which are generally considered to be viral sensors) reduced the focus on important molecules that are specific to fungal pathogenesis. Here, I was expecting discussions on the potential contributions of immune gene polymorphisms in the predisposition to the development of invasive fungal infections. Nonetheless, this chapter nicely compliments and introduces the succeeding chapter on ‘Immunomodulators: What is the Evidence for use in Mycoses?’, which reviewed the evidence for and against the use of granulocyte infusions, colony-stimulating factors, IFN-γ, various interleukins and immunoglobulins for the treatment of invasive fungal infections. The discussion on immune reconstitution syndrome is also a timely addition to this chapter.
The first section also contains two very important chapters dealing with the two major strategies for the prevention of fungal infections, namely antifungal prophylaxis and pre-emptive therapy. These two chapters serve to introduce the principles and some of the management issues discussed in later chapters (sections three and four). Antifungal prophylaxis entails the administration of antifungal drugs to all patients at risk of fungal infection and disease, while in principle, pre-emptive therapy requires routine monitoring and surveillance for the presence of fungi, and the administration of antifungal therapy as soon as it is detected and prior to the onset of clinical illness. I was surprised that the chapter on antifungal prophylaxis was very brief, and that it was more concise than the chapter on pre-emptive therapy. I found this ironic since antifungal prophylaxis is used more often than pre-emptive therapy in modern-day clinical practice. Antifungal prophylaxis is common practice in the care of vulnerable patient populations, such as premature newborns, certain high-risk patients in the intensive care unit, and immunocompromised hosts such as transplant recipients and those with anticipated prolonged neutropenia. Hence, the discussion in this chapter was supposedly tailored towards antifungal prophylaxis in risk-specific patient populations, such as intensive care unit patients, transplant recipients, AIDS patients, newborns and those with hematologic malignancies. However, the bulk of the discussion was mainly on hematologic malignancies and stem cell transplant recipients, and the reader was directed to later chapters for the use of antifungal prophylaxis in solid organ transplants (however, the reference cited was mistakenly the chapter on ‘Prophylaxis and Treatment of Invasive Fungal Infections in Neutropenic Cancer and Hematopoietic Stem Cell Transplant Patients’). For this reader, a brief discussion on antifungal prophylaxis in the other high-risk patient populations would have been desirable, even if only to introduce the basic principles of this practice and its potential benefits and pitfalls. The chapter on ‘Pre-emptive Antifungal Therapy’ was comparatively stronger, although this would have been more aptly titled ‘Diagnosis of Fungal Infections’ since the majority of the data cited were on the use of various diagnostic assays for the detection of established fungal disease and, as the author emphasized, their use for pre-emptive therapy remains limited. For pre-emptive antifungal therapy to work, a highly sensitive and specific laboratory marker that is predictive of invasive fungal disease should be available in real-time. In this chapter, the author discussed the data and the principles behind the use of galactomannan, (1,3)-β-d-glucan and molecular diagnostics (fungal DNA detection), although admittedly, their role in pre-emptive antifungal treatment is still not well defined.
Section two of this textbook consists of five well-crafted chapters discussing the various antifungal drug classes. All the chapters are written comprehensively, with the authors discussing, whenever appropriate, the history of each drug class, the mechanism of action and resistance, pharmacodynamics, pharmacokinetics, spectrum of antifungal activity (including some nonfungal activity such as leishmaniasis), adverse effects, dosing and administration, drug interactions and the overview of clinical applications. It was apparent that the authors were following a similar format of presentation, although the chapter on ‘Pharmacology of Azole Antifungal Agents’ was missing a section on the overview of its clinical application, and in its place a discussion on the benefits and logistics of therapeutic drug monitoring was included. While a full chapter was devoted to flucytosine, there was no chapter dedicated to the other antifungal agents such as griseofulvin, tolnaftate, terbinafine and potassium iodide. There was also no chapter discussing the issues and the data on combination antifungal therapy, which is undoubtedly a highly debated controversial topic with plenty of data that have emerged in recent years. There was also no chapter dedicated to novel drugs in the pipeline. Perhaps, the editors should strongly consider adding this to future editions of this book. The last chapter of section two discusses the other modes of antifungal drug delivery, but while the title is ‘Novel Administrations of Antifungals,’ these modes are not entirely new as they have been used for many years. Indeed, the author even cited the experimental use of aerosolized nystatin as early as 1956. In addition to aerosol, the chapter nicely outlines nonsystemic and noncutaneous methods such as intrathecal, intra-articular, intra-ocular and intrabladder irrigation, and administration via vascular lock and its incorporation in bone cement.
There are nine independent chapters dealing with the management of specific fungal syndromes or pathogens in section three of this book. While most chapters presented comprehensive reviews of various mycoses by discussing the aspects of epidemiology, pathogenesis, clinical features, diagnosis and treatment (chapters on dermatophytosis, invasive candidiasis, invasive aspergillosis, human jyalohyphomycoses, phaeohyphomycoses and pneumocystis), others were specifically focused mainly on management (cryptococcosis, endemic mycoses and zygomycosis). Perhaps a better standardization of the format of every chapter should be considered in subsequent editions. Overall, each chapter provides very practical, evidence-based and/or the most up-to-date information on clinical management of various mycoses, and all chapters cite the most recent guidelines for the management of various fungal infections from the Infectious Disease Society of America. It is generally the case that the information presented in reference textbooks is outdated when it comes out in print, but this textbook contains the most recently published guidelines (references as late as 2009 are included). The authors should be commended for this great effort to keep the content of this textbook as contemporary as possible (although some of the earlier chapters still cite older versions of guidelines [such as the 2004 guidelines for candidiasis], the chapters in section three were noticeably updated prior to print).
The final section consists of seven chapters on fungal infections in specific patient populations. The chapter on ‘Antifungal Management in Risk Groups: Transplant Recipients’ discusses the epidemiology, prevention and treatment of fungal infections in both the solid organ and hematopoietic stem cell transplant populations. It was, therefore, a surprise to read in the subsequent chapter another extensive discussion on fungal infections in stem cell transplants (‘Prophylaxis and Treatment of Fungal Infections in Neutropenic Cancer and Hematopoietic Stem Cell Transplant Patients’). Hence, it would have been preferable to have one full chapter to focus in-depth specifically on issues related to solid organ transplant recipients and discuss the details of fungal disease risk inherent to the various solid organ transplant types. The two chapters that dealt with the pediatric population are a very welcome addition to this general reference textbook since issues related to this vulnerable population are distinct from those of adults. The scientific data presented in this section and the clinical experience and insight of the expert authors on the use of newer antifungal drugs in the pediatric population will be particularly useful in guiding practicing pediatricians in the care of their patients.
The last three chapters of the textbook discuss the issues related to fungal infections in burn patients, the syndrome of allergic bronchopulmonary aspergillosis and fungal infections of the genito-urinary tract. I also suggest that future editions of this textbook should include specific chapters on fungal infections in AIDS patients, fungal infections in patients receiving biological therapies and fungal infections associated with indwelling foreign devices, such as joint prosthesis and cardiac assist devices.
In summary, Antifungal Therapy is a comprehensive textbook that reviews the current state of antifungal therapy in humans. Issues related to drug discovery and clinical development were highlighted, the pharmacology and clinical application of various major antifungal drugs were reviewed, and the management issues of various mycoses and the major at-risk patients were up-to-date and discussed in detail. While a few topics were notably missing or under-emphasized, the textbook succeeds overall as an important reference book that will be useful to students and specialists in infectious diseases and mycology, and other healthcare providers with a specific interest in the care of patients with fungal infections.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.