Introduction

Abstract

Invasive fungal infections (IFIs) have increased in significance in accordance with an increase in the population of at-risk patients, which in turn has been fueled largely by improvements in medical technology. Despite the availability of a greater number of antifungal drugs and drug classes to treat IFIs, outcomes for patients with these infections are still unacceptably poor, including high mortality rates and longer hospital stays, together with increased healthcare-associated costs. A number of factors contribute to the generally poor outcomes in patients with IFIs, including delays in diagnosis (and, hence, delayed initiation of appropriate antifungal therapy) with standard diagnostic techniques, increasing resistance of common fungal pathogens to antifungal agents, and various other drug-, pathogen-, or host-related factors that must be carefully considered when making decisions about how best to individualize and optimize therapy for a particular patient with an IFI. The articles in this supplement to The American Journal of Medicine have been written by widely recognized experts in the field, who examine the various factors that contribute to either a successful or unsuccessful outcome for a patient with an IFI. The focus of the articles is on strategies to improve management of these troublesome and costly infections that are commonly encountered in today's hospital environment. In the first article, Dr. Michael A. Pfaller examines the role of in vitro susceptibility testing in IFI management, with a particular emphasis on its use to detect resistance. Unlike the newer diagnostic techniques, standardized methods are available from both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for reliable in vitro antifungal susceptibility. Dr. Pfaller describes the latest data concerning use of these standardized tests to calculate clinical breakpoints and epidemiologic cutoff values, and how this information may be used to identify fungal strains with different mechanisms of acquired resistance, and to generally improve antifungal management of common IFIs. In the second article, Dr. Luis Ostrosky-Zeichner discusses the drawbacks associated with standard histopathologic and culture-based diagnostics that commonly lead to delayed diagnosis and implementation of appropriate antifungal therapy, thereby enabling fungal burden to increase and lowering the likelihood of a successful outcome. There is a significant need for well-standardized, non–culture-based assays of surrogate markers that may be utilized to enable earlier diagnosis and treatment, provide prognostic information, and/or permit therapeutic monitoring. In this context, Dr. Ostrosky-Zeichner discusses the galactomannan and β-glucan assays, and such newer potential surrogates as mannan antigen, antimannan antibodies, and d-arabinitol, as well as diagnostics based on polymerase chain reaction (PCR). The third article, by Dr. Dimitrios P. Kontoyiannis, focuses on various strategies to manage IFIs, including prophylactic, preemptive, empiric, and targeted therapy approaches, and the incorporation of information about local epidemiology; the spectrum of activity, pharmacokinetic and pharmacodynamic parameters, and the safety profile of different antifungal agents; and unique host-related factors that may affect antifungal activity or safety when optimizing therapy for individual patients. In addition, Dr. Kontoyiannis discusses the potential utility of employing therapeutic monitoring when using lipophilic triazoles as therapy. Focal points of the article include antifungal-related hepatotoxicity, and strategies to diagnose and manage mucormycosis. The final article, by Dr. John R. Perfect, provides an interesting look at how host immunity, and its changes over time, may affect outcomes in patients with IFIs. In particular, Dr. Perfect discusses the phenomenon of immune reconstitution syndrome (IRS) as it pertains to patients with IFIs. There is an increasing appreciation that IRS can complicate the management of patients with IFIs; optimal patient management requires consideration of the possibility of IRS under appropriate circumstances, and application of the “art” of medicine to best manage these patients. Each of the articles in this supplement uses a case-based approach to highlight key points about management of patients with IFIs. It is our hope that readers will find the information in these articles useful in their clinical practice. The author of this article has disclosed the following industry relationships: John R. Perfect, MD, has received a grant from Merck & Co., Inc. and Pfizer for contracted research. Editorial support for this publication was provided by Global Education Exchange, Inc., Freehold, New Jersey.