Recently, the Infectious Diseases Society of America (IDSA) published new guidelines for the treatment of candidiasis [Clin Infect Dis 2009, 48(5):503], replacing the 2004 version. 2004 has seen the introduction of new antifungal drugs such as echinocandins and new triazoles, and papers have been published on them. The new guidelines use these results to answer 15 questions commonly asked in the treatment of candidiasis. We invited experts to analyze the more important of these issues. 1 Candidaemia treatment regimen without neutrophil deficiency a For the initial treatment of most adult patients, fluconazole [loading dose 800 mg (12 mg/kg); followed by 400 mg (6 mg/kg), qd] or echinocandins (caspofungin: loading dose 70 mg, followed by 50 mg/d; micafungin: 100 mg/d; anidulafungin: loading dose 200 mg, followed by 100 mg/d). Echinocandins are recommended for patients with moderate to severe infections or a history of recent azole exposure; fluconazole is recommended for patients with mild to moderate infections and no recent history of azole exposure. The regimen for children is the same as for adults (with dose adjustment). b If cultures are positive for azole-susceptible Candida (e.g., Candida albicans) and the patient is stable, fluconazole may be substituted for echinocandins. c For smooth Candida infections, echinocandins are recommended. Fluconazole or voriconazole is not recommended if not confirmed by drug sensitivity testing. For patients with initial treatment with fluconazole or voriconazole, if clinical symptoms improve and blood cultures are rechecked negative, the course of treatment can be continued with azoles to complete. d For near-smooth Candida infections, fluconazole is recommended. Patients who are initially treated with echinocandins may continue with these drugs to complete the course if clinical symptoms improve and blood cultures are negative. e If the patient is intolerant or does not receive these drugs, amphotericin B [0.5-1.0 mg/(kg・d)] or its liposomes [3-5 mg/(kg・d)] may be used. If the culture result is an azole-susceptible Candida (e.g., Candida albicans) and the patient is stable, fluconazole may be used instead of amphotericin B or its liposomes. f Voriconazole [400 mg (6 mg/kg), bid; followed by 200 mg (3 mg/kg), bid] is effective, but not superior to fluconazole, for Candidaemia. Voriconazole is selected as oral maintenance therapy only for patients with Candida cladococcal or voriconazole-sensitive smooth Candida infections. g In patients with Candidaemia without significant comorbidities, the course of treatment is maintained for 2 weeks after negative blood cultures and significant clinical remission. h Removal of central venous cannula is strongly recommended. Neutrophil deficient i Echinocandins (caspofungin: 70 mg loading dose followed by 50 mg/d; micafungin: 100 mg/d; anidulafungin: 200 mg loading dose followed by 100 mg/d) or liposomal amphotericin B [ 3-5 mg/(kg・d)] are recommended for most patients. j For patients with mild to moderate infection and no recent history of azole exposure, fluconazole [loading dose 800 mg (12 mg/kg); followed by 400 mg (6 mg/kg), qd] may be used. If the patient is suspected of having a co-infection with mycobacteria, voriconazole [400 mg (6 mg/kg) first day, bid; followed by 200 mg (3 mg/kg), bid] may be used. k For smooth Candida infections, the echinocandins are recommended. Liposomal amphotericin B is equally effective, but is more expensive and potentially toxic. In patients who have been treated with voriconazole or fluconazole, azoles may be used to complete the course if clinical symptoms improve and blood cultures are rechecked negative. For Candida subtilis infections, fluconazole or liposomal amphotericin B is recommended for initial treatment and may be used to complete the course in patients who have been treated with echinocandins if clinical status is stable and blood cultures are negative. For Candida graminearum infection, echinocandins, liposomal amphotericin B, or voriconazole may be used. m In patients with Candidaemia without significant comorbidities, the course of treatment is maintained for 2 weeks after negative blood cultures and significant resolution of clinical symptoms and granulocyte deficiency. n Recommend removal of the central venous cannula. Commentary The new guidelines favor echinocandins as the first choice for patients with Candidaemia, with or without granulocyte deficiency. The vast majority of Candida are susceptible to these drugs in vitro, with only a minority of near-smooth Candida being resistant to them. Fluconazole is preferred in those without granulocyte deficiency, but is preferred for patients with mild disease and no history of azole exposure. In granulocyte-deficient individuals, fluconazole is often used prophylactically, thereby reducing its value as a therapeutic agent. In granulocyte-deficient patients, liposomal amphotericin B is preferred; in those without granulocyte deficiency, amphotericin B or its liposomes are used only as a substitute. The guidelines emphasize the selection of drugs based on the results of culture strains, which shows that identification to the level of the species is necessary for pathogenic bacteria of blood-borne infections. However, clinical improvement and fungal clearance should be the main basis when adjusting drugs, and in vitro drug sensitivity results are only for reference. 2 Empirical treatment regimen for suspected invasive candidiasis without neutrophil deficiency a Empirical treatment is the same as that for confirmed diagnosis. Initial treatment is recommended with fluconazole [loading dose 800 mg (12 mg/kg); followed by 400 mg (6 mg/kg), qd] or echinocandins (caspofungin: loading dose 70 mg, followed by 50 mg/d; micafungin: 100 mg/d; anidulafungin: loading dose 200 mg, followed by 100 mg/d). Echinocandins are recommended for patients with moderate to severe infection, or a history of recent azole exposure, or Candida smoothus/Candida klebsiella infection. b If these drugs are not tolerated or available to the patient, amphotericin B [0.5-1.0 mg/(kg・d)] or its liposomes [3-5 mg/(kg・d)] may be used. c Empiric treatment should be reserved for severely ill patients with no known cause of fever in the presence of risk factors for invasive candidiasis and should be based on clinical evaluation of risk factors, serologic markers of invasive candidiasis, and/or culture results from non-sterile sites. Neutrophil deficient patients d Recommend liposomal amphotericin B [3-5 mg/(kg・d)], caspofungin (loading dose 70 mg, followed by 50 mg/d) or voriconazole (6 mg/kg, bid; followed by 3 mg/kg, bid). e Fluconazole [loading dose of 800 mg (12 mg/kg); followed by 400 mg (6 mg/kg), qd] and itraconazole [200 mg (3 mg/kg), bid] may be used as alternatives. f Amphotericin B is also an option, but is more toxic. g If azoles have been used for prophylaxis, they should not be used for empiric therapy. Commentary The empirical treatment options for patients without granulocyte deficiency and for patients with granulocyte deficiency differ widely. For the former, fluconazole and echinocandins are preferred, with amphotericin B or its liposomes as an alternative. It is difficult to define the clinical criteria for empirical treatment of such patients, and a comprehensive judgment should be made based on risk factors, serologic findings, broad-spectrum antibiotic efficacy, and Candida colonization as much as possible to avoid overapplication leading to toxic reactions and drug resistance. For the latter, although empirical treatment can reduce the mortality rate of fungal infection, the number of patients receiving empirical treatment should be minimized, and full use should be made of serological and imaging diagnostic methods to convert empirical treatment to targeted treatment. In such patients, the possibility of mycobacterial infection should be considered in addition to Candida infection, and drugs that can cover both, including liposomal amphotericin B, caspofungin, or voriconazole, should be selected. Amphotericin B is more toxic and fluconazole has a narrow antibacterial spectrum, both of which should not be used. There is less experience with micafungin, anidulafungin and posaconazole. 3 Prophylactic treatment of patients at high risk of candidiasis a For patients with liver, pancreas and small intestine transplantation, fluconazole [200-400 mg (3-6 mg/kg), qd ] or liposomal amphotericin B [1-2 mg/(kg・d)] is recommended as a prophylactic option after surgery for at least 7-14 days. b For ICU patients, prophylactic fluconazole [400 mg (6 mg/kg), qd] is recommended. c For patients with granulocyte deficiency due to chemotherapy, prophylactic fluconazole [400 mg (6 mg/kg), qd], posaconazole (200 mg, tid), or caspofungin (50 mg/d) is recommended in the post-chemotherapy granulocyte deficiency phase. Oral itraconazole (200 mg/d) may also be an alternative, but is less well tolerated by patients. d For patients undergoing stem cell transplantation, prophylactic use of fluconazole [400 mg (6 mg/kg), qd], posaconazole (200 mg, tid), or micafungin (50 mg/d) is recommended during the granulocyte-deficient phase. Commentary Invasive candidiasis occurs in liver, pancreas, and small bowel transplant patients, with liver transplant patients at the highest risk. Despite the lack of research evidence, experts believe that prophylactic treatment should also be administered to small bowel transplant patients. Prophylactic treatment is not required for other solid organ transplant patients. Prophylaxis significantly reduces the incidence of invasive candidiasis in ICU patients, but has not shown an advantage in improving patient survival. Prophylactic antifungal therapy with fluconazole, posaconazole, and echinocandins should be given to patients receiving chemotherapy and stem cell transplantation during the granulocyte-deficient phase. 4 Implications of isolation of Candida from airway secretions a Candida growth in airway secretions is rarely indicative of invasive candidiasis and therefore antifungal therapy should not be administered to such patients. Numerous prospective and retrospective studies, including autopsies, have shown that in invasive candidiasis, culture of airway secretions (including bronchoalveolar lavage fluid) with Candida growth has very low predictive value and should not be used as a basis for initiating antifungal therapy. Commentary Candida pneumonia and lung abscesses are extremely rare. Histologic evidence is required for diagnosis. Studies have confirmed that Candida can often be isolated from airway secretions and is an airway or oropharyngeal colonizing organism with no pathogenic significance. The new guidelines clearly state that antifungal therapy should not be initiated based solely on the isolation of Candida from airway secretions. Such patients do not require antifungal therapy. 5 Other considerations a All patients with Candidaemia should receive an ophthalmologic examination, usually after disease control or correction of granulocyte deficiency. The purpose is to detect and intervene in endophthalmitis in a timely manner, to speculate on the presence of tissue dissemination, and to determine whether a prolonged course of therapy is warranted. b Starting antifungal therapy within 24 hours of a positive blood culture may reduce patient mortality. v Blood cultures should be retested daily or every other day after treatment until the results are negative.