Year: 2009
Type: letter
Abstract: To the Editor—We appreciate the comments of Dr. Kontoyiannis [1] relating to the recently updated Infectious Diseases Society of America treatment guidelines for invasive candidiasis [2]. It is easy to understand his perspective, which represents that of someone who almost exclusively treats severely immunosuppressed individuals. Let us briefly comment on the 2 issues that he raises: (1) the applicability of findings from large, randomized candidemia treatment studies to highly immunosuppressed patients, including those with neutropenia, and (2) the initial approach to antifungal therapy in this patient population with yeast in the bloodstream. To address the first point, we agree that the numerous prospective, randomized trials for the treatment of candidemia have generally not enrolled significant numbers of neutropenic patients, stem cell transplant recipients, or other severely immunocompromised patients. In the earliest of these studies, neutropenic patients were specifically excluded from enrollment into these trials because it was believed that their outcomes might not necessarily reflect those of nonneutropenic patients and that adding this element of heterogeneity might further confound the interpretation of study results [3, 4]. Subsequent studies have allowed enrollment of neutropenic patients, but these patients still constitute a very small proportion of the total enrollment [5-7]. As an example, in the largest of these recent studies, only ∼10% of eligible patients were neutropenic at baseline [7]. Interestingly, the overall success seen in the neutropenic patients was similar to that seen in nonneutropenic patients. Still, these data do not sufficiently address the issue of optimal therapy for invasive candidiasis in the highly immunosuppressed patient. The obvious answer to this conundrum is to design and conduct a properly powered randomized trial comparing different therapies for an exclusively immunosuppressed and/or neutropenic population. Unfortunately, this has proven quite challenging. Large epidemiological surveys of candidemia in the United States demonstrate that only ∼10% of all patients with candidemia are neutropenic [8]. Because of this reality, to conduct a candidemia treatment trial involving exclusively neutropenic patients has been considered unfeasible if one uses conventional methods of determining eligibility (ie, positive culture of blood or specimen from an ordinarily sterile site). For the moment, we are left to make the best of the limited data that are available from small numbers of these patients in randomized clinical trials, nonrandomized studies, and our collective clinical experience. The second issue is equally difficult to address: how does one approach the neutropenic or severely immunosuppressed patient with fungemia due to non-Candida yeasts? Kontoyiannis correctly points out that non-Candida yeasts may account for up to 10% of all bloodstream yeast isolates in selected centers, but how commonly does this occur in the most centers? We simply do not have these data. From our perspective, this most important point emphasizes the need for constant vigilance in this area. We agree that less common yeasts can be important pathogens in these highly vulnerable patients and that any empirical choice for antifungal therapy may prove to be inadequate (eg, giving an echinocandin to treat Cryptococcus neoformans infection) for a particular heavily immunosuppressed patient with yeast in the bloodstream. Unfortunately, no single choice of an antifungal agent adequately addresses each of the possible pathogens. Fortunately, the recent development of early diagnostic techniques (eg, fluorescence in situ hybridization using peptide nucleic acid probes) that are able to reliably identify organisms as Candida spe cies could soon make antifungal selec tion more targeted. Finally, it is important to recognize the limitations of treatment guidelines in general. They are never intended to address every clinical situation, nor can they. Their main intent is to espouse the most reasonable and accepted treatment approaches, based on available data, for the more common and easily defined manifestations of a particular infectious process. With this in mind, we greatly value the perspective of those whose opinions differ from those offered in these guidelines. Potential conflicts of interest. P.G.P. has received research funding from Pfizer, Merck, Astellas, Basilea, and Schering-Plough and has been a consultant (ad hoc) for Merck, Basilea, and Optimer pharmaceuticals. C.A.K. has been on the speakers' bureau for Pfizer and Astellas and has received research grants from Astellas and Merck. T.F.C. has been a consultant for Pfizer, Merck, and Novartis and has received honoraria from Pfizer, Merck, Novartis, Schering-Plough, and Roche Diagnostics. B.-J.K. has been a consultant for Basilea, Novartis, Pfizer, and Schering-Plough and has been on the speakers' bureau for MSD, Pfizer, and Schering-Plough. J.D.S. has received research funding from Merck and Pfizer, has served as a consultant for Merck and Pfizer, and has been on the speakers' bureau for Pfizer, Merck, and Astellas.
Source: Clinical Infectious Diseases
DOI: 10.1086/603586
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1995241004