Practice Guidelines for the Treatment of Candidiasis

Abstract

Infections due to Candida species are the most common of the fungal infections. Candida species produce a broad range of infections, ranging from non-life-threatening mucocutaneous illnesses to invasive process that may involve virtually any organ. Such a broad range of infections requires an equally broad range of diagnostic and therapeutic strategies. This document summarizes current knowledge about treatment of multiple forms of candidiasis and is the guideline of the Infectious Diseases Society of America (IDSA) for the treatment of candidiasis. Throughout this document, treatment recommendations are scored according to the standard scoring scheme used in other IDSA guidelines to illustrate the strength of the underlying data. The document covers 4 major topical areas. The role of the microbiology laboratory. To a greater extent than for other fungi, treatment of candidiasis can now be guided by in vitro susceptibility testing. The guidelines review the available information supporting current testing procedures and interpretive breakpoints and place these data into clinical context. Susceptibility testing is most helpful in dealing with infection due to non-albicans species of Candida. In this setting, especially if the patient has been treated previously with an azole antifungal agent, the possibility of microbiological resistance must be considered. Treatment of invasive candidiasis. In addition to acute hematogenous candidiasis, the guidelines review strategies for treatment of 15 other forms of invasive candidiasis. Extensive data from randomized trials are really available only for therapy of acute hematogenous candidiasis in the nonneutropenic adult. Choice of therapy for other forms of candidiasis is based on case series and anecdotal reports. In general, both amphotericin B and the azoles have a role to play in treatment. Choice of therapy is guided by weighing the greater activity of amphotericin B for some non-albicans species (e.g., Candida krusei) against the lesser toxicity and ease of administration of the azole antifungal agents. Flucytosine has activity against many isolates of Candida but is not often used. Treatment of mucocutaneous candidiasis. Therapy for mucosal infections is dominated by the azole antifungal agents. These drugs may be used topically or systemically and have been proven safe and efficacious. A significant problem with mucosal disease is the propensity for a small proportion of patients to suffer repeated relapses. In some situations, the explanation for such a relapse is obvious (e.g., relapsing oropharyngeal candidiasis in an individual with advanced and uncontrolled HIV infection), but in other patients the cause is cryptic (e.g., relapsing vaginitis in a healthy woman). Rational strategies for these situations are discussed in the guidelines and must consider the possibility of induction of resistance over time. Prevention of invasive candidiasis. Prophylactic strategies are useful if the risk of a target disease is sharply elevated in a readily identified group of patients. Selected patient groups undergoing therapy that produces prolonged neutropenia (e.g., some bone-marrow transplant recipients) or who receive a solid-organ transplant (e.g., some liver transplant recipients) have a sufficient risk of invasive candidiasis to warrant prophylaxis. Relationship between epidemiology of candidal infections and therapy. Although Candida albicans remains the most common pathogen in oropharyngeal and cutaneous candidiasis, non-albicans species of Candida are increasingly frequent problems in both invasive candidiasis [1] and vaginal candidiasis [2]. This is particularly problematic in patients with acutely life-threatening invasive candidal infections. Although the susceptibility of Candida to the currently available antifungal agents can be predicted if the species of the infecting isolate is known (table 1) [1, 3–13], individual isolates do not necessarily follow the general pattern. For example, C. albicans is usually susceptible to all major agents. However, azole resistance for this species is now well described among HIV-infected individuals with relapsing oropharyngeal candidiasis and is also reported sporadically in critically ill adults with invasive candidiasis [14]. For this reason, susceptibility testing for azole resistance is increasingly important in the management of candidiasis in patients. On the other hand, most Candida isolates appear to remain susceptible to amphotericin B, although recent data suggest that isolates of Candida glabrata and C. krusei may require maximal doses of amphotericin B (see below). General patterns of susceptibility of Candida species. Susceptibility testing and drug dosing. Intensive efforts to develop standardized, reproducible, and clinically relevant susceptibility testing methods for the fungi have resulted in the development of the NCCLS M27-A for susceptibility testing of interpretive breakpoints this are available for testing the susceptibility of Candida species to and of these breakpoints are these interpretive breakpoints not be used with other methods testing. Although the M27-A is not the only to a of the M27-A interpretive breakpoints with other methods be with small may produce that are not by of these these interpretive breakpoints place a on in the of the of the azole antifungal The that of and are to therapy. In the case of both and data suggest that isolates may be treated with Although trials to have not used this administration of the of a is a to the of In the case of is and of of by important to therapy. these breakpoints have been on the of data from groups of patients with oropharyngeal and candidiasis and and patients with invasive candidiasis nonneutropenic patients with only Although these are to of interpretive breakpoints for and although of these to other on the of data from in therapy is to consider the of the data of the and drug must be with susceptibility of a therapy. For example, most isolates of Candida are susceptible to but this a and has been only a treatment for mucosal infections. and interpretive breakpoints are not available for amphotericin The NCCLS M27-A not amphotericin isolates of the M27-A methods and of appear to of Although these methods are to are amphotericin B resistance among isolates of C. Candida and Candida isolates of Candida most often readily and clinically amphotericin B However, the of this is and not all isolates are a of data that a proportion of the isolates of C. glabrata and C. krusei may be to amphotericin B of amphotericin B by of a of amphotericin B may not be to this resistance of in vitro of the for susceptibility to amphotericin B amphotericin B than a of the drug the and clinical of these is current therapy for infections due to these species C. and C. krusei) of the possibility of microbiological resistance among the species and and of susceptibility testing. amphotericin B is used to infections due to C. glabrata or C. doses or may be especially in amphotericin B of amphotericin B have been and for in amphotericin B amphotericin B and amphotericin B and amphotericin B have been for in proven candidiasis. These are for therapy of patients who are of or to therapy with amphotericin B in of amphotericin B, or a significant in for adults or for or acute with invasive candidiasis also have been treated with in and clinical that these are but amphotericin B used in and the of randomized trials in proven invasive candidiasis in these infections. These agents the of amphotericin B, and the of these are not known with to Candida infections, amphotericin B remains the standard discussed in the for these guidelines a amphotericin B be in patients who are to this of this or risk of of this (e.g., risk for due to or of agent, such an or These agents are and amphotericin The of these for Candida infections is and the agents appear of appear for treatment of most candidal infections. for patients. The of antifungal in and has been in on of the antifungal agents in patients are B to have in and adults A of in the treatment of candidiasis in that the the and the maximal of drug to of adults and that to be by A of amphotericin B is currently in of is to may of The of with of in be for treatment of life-threatening infections. In with the of in adults may have a of that to by of In with the of in adults have a prolonged of this prolonged in and who are treated for candidiasis. A of has been used and in this to and to therapeutic in The than in patients with particularly in to A recent of and of in HIV-infected document in the treatment of oropharyngeal candidiasis in patients The of has not been in the These guidelines recommendations for treatment of forms of candidiasis. 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To Candida Treatment amphotericin B or or in and of development of candidal infection and the of candidiasis. 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The data have with in bone-marrow transplant The of other agents B, may be by toxicity or Prevention of invasive fungal infection on have been or but both a in the of and of in patient that for the of neutropenia is in patients who are significant risk of invasive candidiasis Such patient groups patients standard for acute bone-marrow or bone-marrow However, in this is important to among these or bone-marrow transplant do not all produce risk and that with and be used to the of To development of invasive fungal infections of Treatment amphotericin B, or Prevention of of and of invasive candidiasis. undergoing liver who have of a group of risk of of of fungal the have been identified risk for invasive fungal infections, especially invasive candidiasis In randomized amphotericin B amphotericin B and may have both fungal and the risk of Candida infections The risk for candidiasis may be to that liver A recent review of transplant a of fungal infections in who for with for also significant of and in patients who and to the of patients risk for invasive candidiasis and the of prophylaxis. The risk of invasive candidiasis of other to be to warrant prophylaxis. Prevention of the significant with invasive candidiasis is and of in to of