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Cited by 1,440Antifungal resistance and susceptibilityFungal Infections and StudiesOcular Infections and Treatments

Guidelines for Treatment of Candidiasis

Open access
Pappas, Peter G., Rex, John H., Sobel, Jack D., Filler, Scott G., Dismukes, William E., Walsh, Thomas J., Edwards, John E.·2004·Clinical Infectious Diseases
DOI 10.1086/380796
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Abstract

Strength of recommendation AGood evidence to support a recommendation for use B Moderate evidence to support a recommendation for use C Poor evidence to support a recommendation D Moderate evidence to support a recommendation against use E Good evidence to support a recommendation against use Quality of evidence 1 Evidence from у1 properly randomized, controlled trial 2 Evidence from у1 well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies (preferably from 11 center); from multiple time-series; or from dramatic results from uncontrolled experiments 3 Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committeesegies for these situations are discussed in the guidelines and must consider the possibility of induction of resistance with prolonged or repeated exposure.Prevention of invasive candidiasis.Prophylactic strategies are useful if the risk of a target disease is sharply elevated in a readily identified patient group.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.

AI snapshot

Written from the paper’s full text.

TL;DR

These IDSA guidelines summarize treatment of candidiasis across invasive, mucocutaneous, and genital syndromes, with graded recommendations. They emphasize species/susceptibility, azoles, amphotericin B, echinocandins, catheter removal, and prophylaxis in high-risk groups.

Key findings

  • Candida species are the most common cause of fungal infections, ranging from non-life-threatening mucocutaneous illness to invasive disease involving virtually any organ.
  • For candidemia in nonneutropenic adults, fluconazole (400 mg/day) and amphotericin B deoxycholate (0.5–0.6 mg/kg per day) were similarly effective; caspofungin (70-mg loading dose then 50 mg/day) was equivalent to amphotericin B deoxycholate (0.6–1.0 mg/kg per day) for invasive candidiasis, and catheter removal is recommended when feasible.
  • Prophylaxis reduced invasive candidiasis in high-risk groups: fluconazole (400 mg/day) reduced fungal infections in liver transplant recipients from 23% to 6% (P<.001), and in preterm infants with birth weights <1000 g, fluconazole reduced invasive candidiasis from 20% to 0% (P=.008).
  • Mucosal and genital disease is dominated by azole therapy; uncomplicated vaginitis occurs in 90% of patients and responds to short-course therapy, whereas complicated vaginitis (~10%) requires ≥7 days of therapy or two 150-mg fluconazole doses 72 h apart.

Methods

  • Design: Infectious Diseases Society of America clinical practice guideline; recommendations are rated using the IDSA–USPHS grading system for strength (A–E) and quality of evidence (1–3).
  • Data: narrative synthesis of randomized trials, observational studies, case series, and expert opinion covering microbiology/susceptibility, invasive candidiasis, mucocutaneous candidiasis, and prevention.
  • Analysis: recommendations are organized by syndrome with objectives, treatment options, outcomes, evidence, values, benefits/harms/costs, and key recommendations; no formal systematic search or meta-analysis is described.

Limitations

  • The paper states that extensive randomized-trial data are available only for therapy of acute hematogenous candidiasis in the nonneutropenic adult; choice of therapy for other forms is based on case series and anecdotal reports.
  • The paper states that antifungal susceptibility testing is not standard of care, echinocandin susceptibility methods are not standardized, meaningful data are lacking for newer triazoles and echinocandins, and pediatric dosing data are limited.
  • Evident from the text: no formal systematic review or search strategy is described, and many recommendations are consensus-based with lower-quality grades (e.g., B-III, C-III).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1086/380796

Cites

324 of 324 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 217 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Variations of the M27-A2 methodology using different media, agar-based MIC methods, and measurements of minimum fungicidal concentrations appear to enhance detection of resistant isolates.

    “Variations of the M27-A2 methodology using different media [6], agar-based MIC methods [12,35,36], and measurements of minimum fungicidal concentrations [11] appear to enhance detection of resistant isolates.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [6] Rex, 1995, Detection of amphotericin B-resistant Candida isolates in a broth-based syste, Antimicrob Agents Chemother source

      Not checked in the free run.

    • cites [12] Wanger, 1995, Comparison of Etest and National Committee for Clinical Laboratory Standards broth macrodilution method for antifungal susceptibility testing: enhanced ability to detect amphotericin B-resistant Candida isolate, Antimicrob Agents Chemother source

      Not checked in the free run.

    • cites [35] Clancy, 1997, Correlation between in vitro susceptibility testing of Candida determined by E-test with microbiologic response to amphotericin B [abstract 14

      Not checked in the free run.

    • cites [36] Clancy, 1999, Correlation between in vitro susceptibility determined by Etest and response to therapy with amphotericin B: results from a multicenter prospective study of candidemi, Antimicrob Agents Chemother source

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    • cites [11] Nguyen, 1998, Do in vitro susceptibility data predict the microbiologic response to amphotericin B?. Results of a prospective study of patients with Candida fungemi, J Infect Dis source

      Not checked in the free run.

  • Premisecitation

    Azole resistance for C. albicans is well described among HIV-infected individuals with recurrent oropharyngeal candidiasis.

    “However, azole resistance for this species is now well described among HIV-infected individuals with recurrent oropharyngeal candidiasis and is also reported sporadically in critically ill adults with invasive candidiasis [25] or in healthy adults [26].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Marr, 1997, Development of fluconazole resistance in Candida albicans causing disseminated infection in a patient undergoing marrow transplantatio, Clin Infect Dis source

      Not checked in the free run.

    • cites [26] Xu, 2000, Clonal and spontaneous origins of fluconazole resistance in Candida albicans, J Clin Microbiol source

      Not checked in the free run.

  • Premisereasoning

    Individual Candida isolates do not necessarily follow the general species susceptibility pattern.

    “Although the susceptibility of Candida to the currently available antifungal agents can be predicted if the species of the infecting isolate is known (table 3) [1,4,6,[11][12][13][14][15][16][17][20][21][22][23][24], individual isolates do not necessarily follow the general pattern.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites table 3

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  • Premisecitation

    The NCCLS M27-A2 methodology does not reliably identify amphotericin B-resistant isolates.

    “The NCCLS M27-A2 methodology does not reliably identify amphotericin B-resistant isolates [6].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Rex, 1995, Detection of amphotericin B-resistant Candida isolates in a broth-based syste, Antimicrob Agents Chemother source

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  • Premisecitation

    The susceptibility of Candida to currently available antifungal agents can be predicted if the species of the infecting isolate is known.

    “Although the susceptibility of Candida to the currently available antifungal agents can be predicted if the species of the infecting isolate is known (table 3) [1,4,6,[11][12][13][14][15][16][17][20][21][22][23][24], individual isolates do not necessarily follow the general pattern.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites table 3

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    • cites [1] Pfaller, 1998, National surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE program. SCOPE Participant Grou, Diagn Microbiol Infect Dis source

      Not checked in the free run.

    • cites [4] Diekema, 2002, Epidemiology of candidemia: 3-year results from the emerging infections and the epidemiology of Iowa organisms stud, J Clin Microbiol source

      Not checked in the free run.

    • cites [6] Rex, 1995, Detection of amphotericin B-resistant Candida isolates in a broth-based syste, Antimicrob Agents Chemother source

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  • Classified as probably not a substantial claim. 34
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  • The quote only partly states this claim. 2

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    Premisereasoning

    The S-DD category indicates that maximization of dosage and bioavailability are critical to successful therapy.

    “The novel category”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Interpretive breakpoints should not be applied to other methods without extensive testing.

    “First, these interpretive breakpoints should not be applied to other methods without extensive testing.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Administration of twice the usual daily dose of fluconazole as a loading dose is a pharmacologically rational way to more rapidly achieve higher steady-state blood concentrations.

    “Although trials to date have not used this method, administration of twice the usual daily dose of fluconazole as a loading dose is a pharmacologically rational way to more rapidly achieve higher steady-state blood concentrations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Among 4 pediatric patients who received voriconazole as salvage therapy, candidemia cleared in 2 of 2 patients and disseminated candidiasis resolved in 1 of 2 patients.

    “Among 4 pediatric patients who received voriconazole as salvage therapy, candidemia cleared in 2 of 2 patients and disseminated candidiasis resolved in 1 of 2 patients [47].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Walsh, 2002, Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in childre, Pediatr Infect Dis J source

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    Premisecitation

    Not all C. lusitaniae isolates are resistant, but therapeutic failure of amphotericin B is well documented.

    “Not all isolates are resistant [11,23,37], but therapeutic failure of amphotericin B is well documented [38].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [11] Nguyen, 1998, Do in vitro susceptibility data predict the microbiologic response to amphotericin B?. Results of a prospective study of patients with Candida fungemi, J Infect Dis source

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    • cites [23] Pfaller, 1994, Strain delineation and antifungal susceptibilities of epidemiologically related and unrelated isolates of Candida lusitaniae, Diagn Microbiol Infect Dis source

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    • cites [37] Viudes, 2002, Two cases of fungemia due to Candida lusitaniae and a literature revie, Eur J Clin Microbiol Infect Dis source

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    • cites [38] Minari, 2001, Candida lusitaniae: a cause of breakthrough fungemia in cancer patient, Clin Infect Dis source

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    Premisecitation

    Voriconazole is as active as fluconazole against esophageal candidiasis, although it was associated with more adverse events in a recent study.

    “It is as active as fluconazole against esophageal candidiasis, although it was associated with more adverse events in a recent study [46].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Ally, 2001, A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patient, Clin Infect Dis source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    When amphotericin B deoxycholate is used to treat infections due to C. glabrata or C. krusei, doses of at least 1 mg/kg per day may be needed, especially in profoundly immunocompromised hosts.

    “When amphotericin B deoxycholate is used to treat infections due to C. glabrata or C. krusei, doses of at least 1 mg/kg per day may be needed, especially in profoundly immunocompromised hosts.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Tests for susceptibility to amphotericin B should always use the deoxycholate rather than the lipid formulation.

    “Also, because of in vitro effects of the lipid, tests for susceptibility to amphotericin B should always use the deoxycholate rather than the lipid formulation [39].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Swenson, 1998, In vitro and in vivo antifungal activity of amphotericin B lipid complex: are phospholipases important, Antimicrob Agents Chemother source

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  • Classified as probably not a substantial claim.

    Premisenone given

    The clinical relevance of the observations about amphotericin B resistance is uncertain.

    “Unfortunately, the clinical relevance of these observations is uncertain.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Susceptibility data may be used to support a change in therapy from a parenteral agent of any class to oral fluconazole.

    “Second, the data may be used to support a change in therapy from a parenteral agent of any class to oral fluconazole.”
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    • cites [27] Rex, 2002, Has antifungal susceptibility testing come of age, Clin Infect Dis source

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    Premisecitation

    Although C. parapsilosis caused only 19% of cases of fungemia in the caspofungin-treated group in the Mora-Duarte study, it was associated with 42% cases of persistent fungemia.

    “Although C. parapsilosis caused only 19% of cases of fungemia in the caspofungin-treated group in that study, it was associated with 42% cases of persistent fungemia.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Mora-Duarte, 2002, Comparison of caspofungin and amphotericin B for invasive candidiasi, N Engl J Med source

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  • Classified as probably not a substantial claim.

    Interpretationcitation

    Consideration of initial use of lipid-associated amphotericin B is appropriate for individuals at high risk of being intolerant of amphotericin B deoxycholate.

    “However, data showing that amphotericin B-induced nephrotoxicity may be associated with an up to 6.6-fold increase in mortality [80] makes consideration of initial use of lipid-associated amphotericin B appropriate for individuals who are at high risk of being intolerant of amphotericin B deoxycholate”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [80] Bates, 2001, Mortality and costs of acute renal failure associated with amphotericin B therap, Clin Infect Dis source

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    Premisecitation

    A phase I and II study of ABLC (2-5 mg/kg per day) in the treatment of hepatosplenic candidiasis in children found that the area under the curve and the maximal concentration of drug were similar to those of adults and that steady-state concentration appeared to be achieved after approximately 7 days of therapy.

    “A phase I and II study of ABLC (2-5 mg/kg per day) in the treatment of hepatosplenic candidiasis in children found that the area under the curve and the maximal concentration of drug were similar to those of adults and that steady-state concentration appeared to be achieved after ∼7 days of therapy [83].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Walsh, 1997, Safety, tolerance, and pharmacokinetics of amphotericin B lipid complex in children with hepatosplenic candidiasi, Antimicrob Agents Chemother source

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    Premisecitation

    Caspofungin has been shown to be as effective as both amphotericin B deoxycholate and fluconazole when used as therapy for oropharyngeal and esophageal candidiasis.

    “Caspofungin has been shown to be as effective as both amphotericin B deoxycholate and fluconazole when used as therapy for oropharyngeal and esophageal candidiasis [57][58][59][60].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [57] Sable, 2002, Safety and tolerability of caspofungin acetate in the treatment of fungal infection, Transpl Infect Dis source

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    • cites [58] Arathoon, 2002, Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiasi, Antimicrob Agents Chemother source

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    • cites [59] Villanueva, 2001, A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagiti, Clin Infect Dis source

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  • May combine two claims.

    Premisecitation

    Both in vivo and clinical studies indicate that lipid-associated amphotericin B compounds are less toxic but as effective as amphotericin B deoxycholate when used in appropriate dosages.

    “Both in vivo and clinical studies indicate that these compounds are less toxic but as effective as amphotericin B deoxycholate when used in appropriate dosages [76,77].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [76] Hiemenz, 1996, Lipid formulations of amphotericin B: recent progress and future direction, Clin Infect Dis source

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    • cites [77] Rex, 1998, Fungal infections in iatrogenically compromised host, Adv Intern Med

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  • May combine two claims.

    Interpretationreasoning

    These data suggest that echinocandins may be used successfully for treatment of C. parapsilosis fungemia but that the physician should be aware of the possibility that this species might respond less readily to this class of agents.

    “Thus, these data suggest that echinocandins may be used successfully for treatment of C. parapsilosis fungemia but that the physician should be aware of the possibility that this species might respond less readily to this class of agents.”
    Quote in the paperSubstantial claim

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    Premisecitation

    The echinocandin class agents do not appear to have significant activity against Cryptococcus neoformans or against filamentous fungi other than Aspergillus.

    “Of particular relevance for use as empirical treatment, the agents of this class do not appear to have significant activity against Cryptococcus neoformans or against filamentous fungi other than Aspergillus [56].”
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    • cites [56] Kurtz, 2001, Glucan synthase inhibitors as antifungal agent, Adv Protein Chem

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    Premisecitation

    Mora-Duarte et al. found that caspofungin (70 mg loading dose followed by 50 mg/day in adults) was equivalent to but better tolerated than amphotericin B deoxycholate (0.6-1.0 mg/kg per day) for cases of invasive candidiasis.

    “Likewise, Mora-Duarte et al. [17] found that caspofungin (70mg loading dose followed by 50 mg/day in adults) was equivalent to but better tolerated than was amphotericin B deoxycholate (0.6-1.0 mg/kg per day) for cases of invasive candidiasis (83% of which were candidemia, 10% of which were peritonitis, and 7% of which were miscellaneous cases).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Mora-Duarte, 2002, Comparison of caspofungin and amphotericin B for invasive candidiasi, N Engl J Med source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Candida bloodstream infections are often associated with clinical evidence of sepsis syndrome and high associated attributable mortality.

    “Candida bloodstream infections are increasingly frequent [101,102] and are often associated with clinical evidence of sepsis syndrome and high associated attributable mortality [103, 104].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [103] Hadley, 2002, Candidemia as a cause of septic shock and multiple organ failure in nonimmunocompromised patient, Crit Care Med source

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    • cites [104] Wey, 1988, Hospital acquired candidemia: the attributable mortality and excess length of sta, Arch Intern Med source

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  • May combine two claims.

    Premisecitation

    Candidemia due to C. parapsilosis has increased in frequency in pediatric populations and appears to be associated with a lower mortality rate than is candidemia due to other species of Candida.

    “Candidemia due to C. parapsilosis has increased in frequency in pediatric populations and appears to be associated with a lower mortality rate than is candidemia due to other species of Candida [110-113].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [110] Levy, 1998, Emergence of Candida parapsilosis as the predominant species causing candidemia in childre, Clin Infect Dis source

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    • cites [111] Kossoff, 1998, Candidemia in a neonatal intensive care unit: trends during fifteen years and clinical features of 111 case, Pediatr Infect Dis J source

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    • cites [112] Coleman, 1998, Importance of Candida species other than Candida albicans as opportunistic pathogen, Med Mycol

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    • cites [113] Viscoli, 1999, Candidemia in cancer patients: a prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC, Clin Infect Dis source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Candida bloodstream infections are increasingly frequent.

    “Candida bloodstream infections are increasingly frequent [101,102] and are often associated with clinical evidence of sepsis syndrome and high associated attributable mortality [103, 104].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [101] Asmundsdottir, 2002, Increasing incidence of candidemia: results from a 20-year nationwide study in Icelan, J Clin Microbiol source

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    • cites [102] Banerjee, 1991, Secular trends in nosocomial primary bloodstream infections in the United States, 1980–198, Am J Med source

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  • May combine two claims.

    Premisecitation

    Caspofungin was better tolerated and had a superior response rate in a predefined secondary analysis of evaluable patients.

    “Caspofungin was better tolerated and had a superior response rate in a predefined secondary analysis of evaluable patients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Mora-Duarte, 2002, Comparison of caspofungin and amphotericin B for invasive candidiasi, N Engl J Med source

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  • May combine two claims.

    Premisecitation

    Caspofungin has excellent clinical activity, broad-spectrum activity against Candida species, and a low rate of treatment-related adverse events.

    “its excellent clinical activity [17], its broad-spectrum activity against Candida species, and a low rate of treatment-related adverse events make it a suitable choice for initial therapy in adults (A-I).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Mora-Duarte, 2002, Comparison of caspofungin and amphotericin B for invasive candidiasi, N Engl J Med source

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  • May combine two claims.

    Premisecitation

    There are no randomized studies of catheter removal for candidemia, and a recent exhaustive review demonstrates the limitations of the available data.

    “There are, however, no randomized studies of this topic, and a recent exhaustive review [119] clearly demonstrates the limitations of the available data.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [119] Nucci, 2002, Should vascular catheters be removed from all patients with candidemia?. An evidence-based revie, Clin Infect Dis source

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    Interpretationcitation

    Breakthrough or persistence of candidemia during antifungal therapy suggests an infected intravascular device, significant immunosuppression, or microbiological resistance.

    “Breakthrough (or persistence of) candidemia in the face of ongoing antifungal therapy suggests the possibility of an infected intravascular device [135], significant immunosuppression [136], or microbiological resistance.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [135] Blumberg, 1996, Failure of systemic empirical treatment with amphotericin B to prevent candidemia in neutropenic patients with cance, Clin Infect Dis source

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    • cites [136] Uzun, 2001, Risk factors and predictors of outcome in patients with cancer and breakthrough candidemi, Clin Infect Dis source

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    Premisecitation

    Amphotericin B deoxycholate has a broader spectrum than fluconazole.

    “many authorities prefer amphotericin B deoxycholate (у0.7 mg/kg per day) [126, 127] because of its broader spectrum.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [126] Edwards, 1997, International conference for the development of a consensus on the management and prevention of severe candidal infection, Clin Infect Dis source

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    • cites [127] Buchner, 2002, Treatment of severe Candida infections in high-risk patients in Germany: consensus formed by a panel of interdisciplinary investigator, Eur J Clin Microbiol Infect Dis source

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    Premisecitation

    Candidemia increased the length of hospitalization by 22 days and increased costs by $34,000-$44,000.

    “One study found that candidemia increased the length of hospitalization by 22 days and increased costs by $34,000-$44,000 [138].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [138] Rentz, 1998, The impact of candidemia on length of hospital stay, outcome, and overall cost of illnes, Clin Infect Dis source

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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Early antifungal therapy is more likely to succeed in neutropenic patients.

    “Early antifungal therapy is more likely to succeed in neutropenic patients.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    Fluconazole has a limited spectrum.

    “Fluconazole may be inappropriate because of prior exposure and its limited spectrum.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Candida is the fourth most common bloodstream isolate and the most common invasive fungal infection in critically ill nonneutropenic patients.

    “Although Candida is now the fourth most common bloodstream isolate and is the most common invasive fungal infection in critically ill nonneutropenic patients, accurate early diagnostic tools for invasive candidiasis are lacking.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Advanced fungal infection is associated with high morbidity and mortality.

    “Advanced infection is associated with high morbidity and mortality.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Treatment of chronic disseminated candidiasis continues throughout chemotherapy.

    “Treatment of chronic disseminated candidiasis in such patients continues throughout chemotherapy [160].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [160] Walsh, 1995, Successful treatment of hepatosplenic candidiasis through repeated episodes of neutropeni, Cancer source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Amphotericin B is efficacious but must be administered intravenously; fluconazole can be given orally.

    “Amphotericin B, although efficacious, must be administered intravenously.Fluconazole can be given orally.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The neonatal candidiasis syndrome is thought to be secondary to contamination of the amniotic fluid, and in healthy-term infants it is usually limited to the skin and resolves with topical therapy.

    “This syndrome is thought to be secondary to contamination of the amniotic fluid, and, in healthy-term infants, this process is usually limited to the skin and resolves with topical therapy [164].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [164] Kam, 1975, Congenital cutaneous candidiasi, Am J Dis Child

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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Premature discontinuation of antifungal therapy may lead to recurrent infection.

    “Premature discontinuation of antifungal therapy may lead to recurrent infection.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Itraconazole has similar breakthrough fungal infection rates and mortality but significantly less toxicity compared with amphotericin B deoxycholate.

    “When compared with amphotericin B deoxycholate (mean daily dose, 0.7 mg/kg), itraconazole (200 mg iv q12h for 2 days, 200 mg iv per day for 12 days, and then 400-mg solution po per day) showed similar breakthrough fungal infection rates and mortality but significantly less toxicity (A-I) [144].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [144] Boogaerts, 2001, Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy—a randomized, controlled tria, Ann Intern Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Liposomal amphotericin B has similar overall clinical efficacy but superior safety and a decreased rate of documented breakthrough fungal infections compared with amphotericin B deoxycholate, particularly in bone marrow transplant recipients.

    “When compared with amphotericin B deoxycholate (median dose, 0.6 mg/ kg per day), liposomal amphotericin B (median dose, 3 mg/kg per day) showed similar overall clinical efficacy but demonstrated superior safety and a decreased rate of documented breakthrough fungal infections, particularly in recipients of bone marrow transplants (A-I) [151].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [151] Walsh, 1999, Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropeni, N Engl J Med source

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  • May combine two claims.

    Premisenone given

    Chronic disseminated candidiasis is not acutely life-threatening but requires prolonged therapy to produce a cure.

    “This syndrome is not acutely life-threatening but does require prolonged therapy to produce a cure.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Treatment of persistently febrile patients who have candiduria but who lack evidence for infection at other sites may treat occult disseminated candidiasis.

    “Treatment of persistently febrile patients who have candiduria but who lack evidence for infection at other sites may treat occult disseminated candidiasis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Inappropriate therapy may select for resistant organisms.

    “Inappropriate therapy may select for resistant organisms.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Treatment of appropriately selected patients may reduce the risk of ascending and/or hematogenously disseminated disease.

    “Treatment of appropriately selected patients may reduce the risk of ascending and/or hematogenously disseminated disease.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Candiduria may rarely be the source of subsequent dissemination or a marker of acute hematogenous dissemination.

    “candiduria may rarely be the source of subsequent dissemination [170] or a marker of acute hematogenous dissemination [166].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [170] Ang, 1993, Candidemia from a urinary tract source: microbiological aspects and clinical significanc, Clin Infect Dis source

      Not checked in the free run.

    • cites [166] Wise, 1993, Fungal infections of the genitourinary syste, J Urol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Candida species are now the organisms most frequently isolated from the urine of patients in surgical ICUs.

    “Candida species are now the organisms most frequently isolated from the urine of patients in surgical ICUs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Even with apparently successful local or systemic antifungal therapy for candiduria, relapse is frequent, and this likelihood is increased by continued use of a urinary catheter.

    “Even with apparently successful local or systemic antifungal therapy for candiduria, relapse is frequent, and this likelihood is increased by continued use of a urinary catheter.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Candiduria in neutropenic patients, critically ill patients in ICUs, infants with low birth weight, and recipients of a transplant may be an indicator of disseminated candidiasis.

    “Candiduria in neutropenic patients, critically ill patients in ICUs, infants with low birth weight, and recipients of a transplant may be an indicator of disseminated candidiasis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Urinary candidiasis includes an ill-defined group of syndromes.

    “Urinary candidiasis includes an ill-defined group of syndromes [166].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [166] Wise, 1993, Fungal infections of the genitourinary syste, J Urol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treatment with fluconazole will briefly clear funguria in approximately one-half of treated patients, but recurrence is prompt, selection of resistant Candida species is possible, and therapy does not appear to alter clinical outcome.

    “Treatment with fluconazole will briefly clear funguria in approximately one-half of treated patients, but recurrence is prompt, selection of resistant Candida species is possible, and therapy does not appear to alter clinical outcome [168].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [168] Sobel, 2000, Candiduria: a randomized, double-blind study of treatment with fluconazole and placeb, Clin Infect Dis source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most cases of laryngitis have been managed with amphotericin B therapy, but milder cases have been successfully managed with fluconazole therapy.

    “Most cases have been managed with amphotericin B therapy, but milder cases been successfully managed with fluconazole therapy [179,180].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [179] Wang, 1997, Laryngeal candidiasis in childre, Scand J Infect Dis source

      Not checked in the free run.

    • cites [180] Neuenschwander, 2001, Laryngeal candidiasi, Ear Nose Throat J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fluconazole (200 mg/day for 14 days) hastened the time to negative urine culture but the frequency of negative urine culture results was the same in both treatment groups 2 weeks after the end of therapy.

    “A recently completed placebo-controlled trial found that fluconazole (200 mg/day for 14 days) hastened the time to negative results of urine culture but that the frequency of negative urine culture results was the same in both treatment groups 2 weeks after the end of therapy (∼60% for catheterized patients and ∼73% for noncatheterized patients) [168].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [168] Sobel, 2000, Candiduria: a randomized, double-blind study of treatment with fluconazole and placeb, Clin Infect Dis source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisereasoning

    Management of Candida arthritis of the hip requires open drainage.

    “In particular, management of Candida arthritis of the hip requires open drainage.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    Because of the severe morbidity and potential mortality associated with laryngeal candidiasis, rapid clinical diagnosis and prompt initiation of therapy are important and outweigh any adverse effects of antifungal therapy.

    “because of the severe morbidity and potential mortality associated with laryngeal candidiasis, rapid clinical diagnosis and prompt initiation of therapy are important and outweigh any adverse effects of antifungal therapy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Definitive diagnosis of Candida pneumonia requires histopathological confirmation.

    “Definitive diagnosis of Candida pneumonia requires histopathological confirmation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). The quote only partly states this claim.

    Interpretationnone given

    The high morbidity associated with untreated candidal osteomyelitis makes aggressive surgical and medical therapy appropriate.

    “The high morbidity associated with untreated disease makes aggressive surgical and medical therapy appropriate.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Premisenone given

    Multiple observational studies have been reported, most of which have used intravenous amphotericin B as the primary therapy for candidal osteomyelitis, sometimes followed by an azole.

    “Multiple observational studies have been reported, most of which have used intravenous amphotericin B as the primary therapy, sometimes followed by a course of treatment with an azole antifungal agent.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Injudicious use of antifungal therapy for patients with tracheobronchial colonization or oropharyngeal contamination of respiratory secretions may lead to selection of resistant organisms.

    “Injudicious use of antifungal therapy for patients with tracheobronchial colonization or oropharyngeal contamination of respiratory secretions may lead to selection of resistant organisms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Firm diagnosis of Candida pneumonia and laryngitis is elusive and requires histopathological confirmation.

    “Firm diagnosis of these disease entities is elusive and requires histopathological confirmation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Case reports have documented cures of Candida arthritis with intravenous amphotericin B and with fluconazole when administered in conjunction with adequate drainage.

    “Case reports have documented cures with administration of intravenous amphotericin B [195] and with fluconazole when administered in conjunction with adequate drainage.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [195] Harris, 2000, Candidal arthritis in infants previously treated for systemic candidiasis during the newborn period: report of three case, Pediatr Emerg Care source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    If not diagnosed and treated promptly, laryngitis may lead to airway obstruction and respiratory arrest.

    “If not diagnosed and treated promptly, laryngitis may lead to airway obstruction and respiratory arrest.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Untreated candidal osteomyelitis leads to crippling disability.

    “Untreated disease leads to crippling disability.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Addition of amphotericin B deoxycholate to bone cement appears safe and may be of value in complicated cases.

    “Addition of amphotericin B deoxycholate to bone cement appears safe and may be of value in complicated cases [193].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [193] Marra, 2001, Amphotericin B-loaded bone cement to treat osteomyelitis caused by Candida albicans, Can J Surg

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both amphotericin B and fluconazole achieve therapeutic biliary concentrations.

    “Both agents achieve therapeutic biliary concentrations, and local instillation is not needed [215].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [215] Adamson, 1989, Amphotericin B in treatment of Candida cholecystiti, Pediatr Infect Dis J source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    These infections are associated with high morbidity and mortality, justifying aggressive medical and surgical therapy.

    “These infections are associated with high morbidity and mortality, justifying aggressive medical and surgical therapy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Routine treatment of Candida isolated following prompt and definitive repair of an acutely perforated viscus in otherwise healthy patients without signs of sepsis is probably not needed and could lead to selection of resistant organisms.

    “Routine treatment of Candida isolated following prompt and definitive repair of an acutely perforated viscus in otherwise healthy patients without signs of sepsis is probably not needed and could lead to selection of resistant organisms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Candida meningitis often follows candidemia in newborn infants and has a high propensity for relapse.

    “Candida meningitis often follows candidemia in newborn infants [234] and has a high propensity for relapse.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [234] Fernandez, 2000, Candidal meningitis in neonates: a 10-year revie, Clin Infect Dis source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Removal of infected valves, resection of infected peripheral veins, and debridement of infected pericardial tissue are almost always required for successful therapy of candidal endocarditis, pericarditis, and suppurative phlebitis.

    “removal of infected valves, resection of infected peripheral veins, and debridement of infected pericardial tissue are almost always required for successful therapy [218,219].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [218] Muehrcke, 1995, Surgical and long-term antifungal therapy for fungal prosthetic valve endocarditi, Ann Thorac Surg source

      Not checked in the free run.

    • cites [219] Schrank, 1995, Purulent pericarditis caused by Candida species: case report and revie, Clin Infect Dis source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    Surgical patients with recurrent gastrointestinal perforation are at increased risk for Candida peritonitis and may benefit from prophylactic antifungal therapy.

    “Surgical patients with recurrent gastrointestinal perforation are at increased risk for Candida peritonitis and may benefit from prophylactic antifungal therapy (B-I).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Candida is usually part of a polymicrobial infection, and therapy directed toward Candida species is indicated, particularly when Candida organisms are isolated as part of a complex infection or in an immunocompromised patient.

    “Candida is usually part of a polymicrobial infection, and case series suggest that therapy directed toward Candida species is indicated, particularly when Candida organisms are isolated as part of a complex infection or in an immunocompromised patient [205][206][207][208][209].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [205][206][207][208][209]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The required duration of therapy for all forms of Candida peritonitis is not well defined.

    “The required duration of therapy for all forms of Candida peritonitis is not well defined and should be guided by the patient's response.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Candida endocarditis has a propensity for relapse and requires careful follow-up for at least 1 year.

    “Candida endocarditis has a propensity for relapse and requires careful follow-up for at least 1 year [227].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [227] Johnston, 1991, Late recurrent Candida endocarditi, Chest source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Candidal myocarditis is usually part of the syndrome of disseminated candidiasis, is clinically silent, and is treated as part of the therapy of disseminated disease.

    “Candidal myocarditis is usually part of the syndrome of disseminated candidiasis, is clinically silent, and is treated as part of the therapy of disseminated disease [224].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [224] Nosanchuk, 2002, Fungal myocarditi, Front Biosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Voriconazole is as efficacious as fluconazole for esophageal candidiasis but is associated with a higher rate of treatment-related adverse events.

    “Voriconazole (200 mg b.i.d. for a median duration of 14 days) is as efficacious as fluconazole (400 mg loading dose followed by 200 mg/day for a median duration of 15 days) but is associated with a higher rate of treatment-related adverse events [46].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Ally, 2001, A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patient, Clin Infect Dis source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Uncomplicated vaginitis is seen in 90% of patients and responds readily to short-course oral or topical therapy with any of the listed therapies, including single-dose regimens.

    “Uncomplicated vaginitis is seen in 90% of patients and responds readily to short-course oral or topical therapy with any of the therapies listed above, including the single-dose regimens (A-I).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Complicated vaginitis is seen in approximately 10% of patients and requires antimycotic therapy for at least 7 days, either daily topical therapy or two 150-mg doses of fluconazole 72 h apart.

    “In contrast, the complicated vaginitis seen in ∼10% of patients requires antimycotic therapy for у7 days, either daily as topical therapy or as two 150-mg doses of fluconazole administered 72 h apart [314] (A-I).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [314] Sobel, 2001, Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazol, Am J Obstet Gynecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fluconazole is superior to ketoconazole, itraconazole capsules, and flucytosine for treatment of esophageal candidiasis.

    “Fluconazole is superior to ketoconazole, itraconazole capsules, and flucytosine for the treatment of esophageal candidiasis [278][279][280].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [278] Laine, 1992, Fluconazole compared with ketoconazole for the treatment of Candida esophagitis in AIDS: a randomized tria, Ann Intern Med source

      Not checked in the free run.

    • cites [279] Barbaro, 1996, Fluconazole versus itraconazole for Candida esophagitis in acquired immunodeficiency syndrome. Candida esophagiti, Gastroenterology source

      Not checked in the free run.

    • cites [280] Barbaro, 1995, Fluconazole vs. flucytosine in the treatment of esophageal candidiasis in AIDS patients: a double-blind, placebo-controlled stud, Endoscopy source

      Not checked in the free run.

74 of 74

  • The paper relies on this without support.

    Prophylactic strategies are useful if the risk of a target disease is sharply elevated in a readily identified patient group.

    “Prophylactic strategies are useful if the risk of a target disease is sharply elevated in a readily identified patient group.”

  • The paper relies on this without support.

    Selected patient groups undergoing therapy that produces prolonged neutropenia or who receive a solid-organ transplant have a sufficient risk of invasive candidiasis to warrant prophylaxis.

    “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.”

  • The paper relies on this without support.

    Susceptibility testing of fungi is not considered a routine testing procedure in many laboratories, is not always promptly available, and is not universally considered as the standard of care.

    “However, susceptibility testing of fungi is not considered a routine testing procedure in many laboratories, is not always promptly available, and is not universally considered as the standard of care.”

  • The paper relies on this without support.

    Extensive data from randomized trials are available only for therapy of acute hematogenous candidiasis in the nonneutropenic adult.

    “Extensive data from randomized trials are available only for therapy of acute hematogenous candidiasis in the nonneutropenic adult.”

  • The paper relies on this without support.

    Choice of therapy for other forms of candidiasis is based on case series and anecdotal reports.

    “Choice of therapy for other forms of candidiasis is based on case series and anecdotal reports.”

  • The paper relies on this without support.

    Azole antifungal agents are safe and efficacious for mucosal infections.

    “These drugs may be used topically or systemically and are safe and efficacious.”

  • The paper relies on this without support.

    A significant problem with mucosal disease is the propensity for a small proportion of patients to have repeated relapses.

    “A significant problem with mucosal disease is the propensity for a small proportion of patients to have repeated relapses.”

  • The paper relies on this without support.

    In some situations the explanation for mucosal relapse is obvious, but in other patients the cause is cryptic.

    “In some situations, the explanation for such a relapse is obvious (e.g., recurrent 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).”

  • The paper relies on this without support.

    Most Candida isolates appear to remain susceptible to amphotericin B.

    “On the other hand, most Candida isolates appear to remain susceptible to ampho-tericin B”

  • The paper relies on this without support.

    Recent data suggest that isolates of Candida glabrata and C. krusei may require maximal doses of amphotericin B.

    “although recent data suggest that isolates of Candida glabrata and C. krusei may require maximal doses of amphotericin B”

  • The paper relies on this without support.

    Antifungal susceptibility testing has not achieved the status of a standard of care and is not widely available.

    “Antifungal susceptibility testing has not achieved the status of a standard of care and is not widely available”

  • The paper relies on this without support.

    All the reviewed antifungal compounds appear to have significant activity against Candida species.

    “Although all these compounds appear to have significant activity against Candida species”

  • The paper relies on this without support.

    Itraconazole is well known to be active against mucosal forms of candidiasis.

    “Itraconazole is well known to be active against mucosal forms of candidiasis”

  • The paper relies on this without support.

    Caspofungin appears to be active against all Candida species.

    “This agent appears to be active against all Candida species”

  • The paper relies on this without support.

    The in vitro activity of anidulafungin and micafungin against Candida species appears quite similar to that of caspofungin.

    “The in vitro activity of the other 2 agents in this category (anidulafungin and micafungin) against Candida species appears quite similar to that of caspofungin”

  • The paper relies on this without support.

    The majority of the experience with amphotericin B is with its classic deoxycholate preparation.

    “The majority of the experience with amphotericin B is with its classic deoxycholate preparation.”

  • The paper relies on this without support.

    No form of candidiasis is known in which a lipid-associated formulation of amphotericin B is superior to amphotericin B deoxycholate.

    “We are not aware of any forms of candidiasis for which a lipid-associated formulation of amphotericin B is superior to amphotericin B deoxycholate [70]”

  • The paper relies on this without support.

    No situation is known in which a lipid-associated formulation of amphotericin B would be contraindicated.

    “but we are also not aware of any situations in which a lipid-associated formulation would be contraindicated.”

  • The paper relies on this without support.

    The optimal dosages of lipid-associated amphotericin B compounds for serious Candida infections are unclear.

    “The optimal dosages of these compounds for serious Candida infections is unclear”

  • The paper relies on this without support.

    Data on dosing for antifungal agents in pediatric patients are limited.

    “Data on dosing for the antifungal agents in pediatric patients are limited.”

  • The paper relies on this without support.

    Amphotericin B deoxycholate has low toxicity in neonates.

    “Neonates with disseminated candidiasis are usually treated with amphotericin B deoxycholate because of its low toxicity and because of the relative lack of experience with other agents in this population.”

  • The paper relies on this without support.

    There is a relative lack of experience with antifungal agents other than amphotericin B deoxycholate in neonates.

    “Neonates with disseminated candidiasis are usually treated with amphotericin B deoxycholate because of its low toxicity and because of the relative lack of experience with other agents in this population.”

  • The paper relies on this without support.

    Sterilization of CSF often precedes eradication of parenchymal infection in Candida meningitis.

    “Sterilization of the CSF often precedes eradication of parenchymal infection.”

  • The paper relies on this without support.

    Untreated Candida meningitis is lethal.

    “Untreated disease is lethal.”

  • The paper relies on this without support.

    Many individuals have asymptomatic oropharyngeal colonization with Candida species, and treatment frequently does not result in microbiological cure.

    “Many individuals have asymptomatic oropharyngeal colonization with Candida species, and treatment frequently does not result in microbiological cure.”
25 of 25

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Some Candida spp. including C. lusitaniae and C. guilliermondii, besides C. glabrata, are capable of expressing resistance to amphotericin B.

    “Additionally, some Candida spp. including C. lusitaniae and C. guilliermondii, besides C. glabrata, are capable of expressing resistance to amphotericin B [127].”

    From <i>Candida</i>Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents (2013) · cites this paper as [127]

  • Candida infections range from superficial mucosal and dermal infections to hematogenously disseminated infection with mortality approaching 40% in some cases.

    “These infections range from superficial mucosal and dermal infections, such as thrush, vaginal yeast infections, and diaper rash, to hematogenously disseminated infection with sizable mortality rates (approaching 40% in some cases) (21, 148, 202).”

    From <i>Candida albicans</i> Biofilms and Human Disease (2015) · cites this paper as [148]

Cites

Flagged first, then by citations

Research works printed but not linked: 33

  1. Ostrosky-Zeichner, 2002, Voriconazole salvage treatment of invasive candidiasis: experience from open-label compassionate use protocols [abstract 352
  2. Rex, 1998, Susceptibility testing of current Candida bloodstream isolates from Mycoses Study Group (MSG) Collaborative Study #34: isolates of C. krusei are often resistant to both fluconazole and amphotericin B [abstract 324, 136
  3. NCCLS, 2002, Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard. NCCLS document M27-A2
  4. Clancy, 1998, Correlation of fluconazole MIC and response to therapy for patients with candidemia due to C. albicans and non-C. albicans spp: results of a multicenter prospective study of candidemia [abstract 98
  5. Clancy, 1997, Correlation between in vitro susceptibility testing of Candida determined by E-test with microbiologic response to amphotericin B [abstract 14
  6. Boogaerts, 1996, Pharmacokinetics and safety of seven days of intravenous (IV) itraconazole followed by two weeks oral itraconazole solution in patients with hematological malignancy [abstract A87
  7. Hachem, 2000, An open, noncomparative multicenter study to evaluate efficacy and safety of posaconazole (SCH 56592) in the treatment of invasive fungal infections refractory to or intolerant of standard therapy [abstract 1109
  8. Skiest, 1999, Treatment of azole-refractory candidiasis in HIV disease [abstract 1162
  9. Nieto, 2000, Posaconazole equivalent to fluconazole in the treatment of oropharyngeal candidiasis [abstract 1108
  10. Vazquez, 2000, Posaconazole compared to fluconazole for oral candidiasis in HIV-positive patients [abstract 1107
  11. Beale, 2001, Randomized, double-blind study of the safety and antifungal activity of ravuconazole relative to fluconazole in esophageal candidiasis [abstract J-1621
  12. Pettengell, 1999, A multicenter study to determine the minimal effective dose of FK463 for the treatment of esophageal candidiasis in HIV-positive patients [abstract 1421
  13. Pettengell, 2000, A multicenter study of the echinocandin antifungal FK463 for the treatment of esophageal candidiasis in HIV positive patients [J-1104
  14. Suleiman, 2002, Open-label study of micafungin in the treatment of esophageal candidiasis [abstract M-892, 394
  15. Brown, 2000, Phase 1 dose optimization study for V-echinocandin [abstract 1105, 371
  16. Kohno, 2001, A multicenter, open-label clinical study of FK463 in patients with deep mycosis in Japan [abstract J-834
  17. Kontoyiannis, 2001, Initial experience with FK463 for the treatment of candidemia in cancer patients [abstract J-1629
  18. Van Burik, 2002, Randomized, double-blind trial of micafungin versus fluconazole for prophylaxis of invasive fungal infections in patients undergoing hematopoietic stem cell transplant, NIAID/BAMSG Protocol 46 [abstract M-1238
  19. Groll, 1997, Penetration of lipid formulations of amphotericin B into cerebrospinal fluid and brain tissu
  20. Townsend, 2001, Pharmacokinetic evaluation of echinocandin FK463 in pediatric and adult patients [abstract 024, 99
  21. Seibel, 2000, A phase I study to determine the safety and pharmacokinetics of FK463 (echinocandin) in febrile neutropenic pediatric patients [abstract J-1648
  22. Walsh, 2002, Pharmacokinetics of caspofungin in pediatric patients [abstract M-896
  23. Anaissie, 1995, Amphotericin B lipid complex (ABLC) versus amphotericin B (AMB) for treatment of hematogenous and invasive candidiasis: a prospective, randomized, multicenter trial [abstract LM21
  24. Sylvester, 2002, Site of Candida colonization and the risk of Candida infection in critically ill surgical patients [abstract 15
  25. Walsh, 2002, Decisions about voriconazole versus liposomal amphotericin B [letter, N Engl J Med, 346, 1499, 10.1056/NEJM200205093461915 · DOI · Paper page
  26. Walsh, 2002, Voriconazole versus liposomal amphotericin B for empirical antifungal therapy [reply, N Engl J Med, 346, 1746, 10.1056/NEJM200201243460403 · DOI · Paper page
  27. Kam, 1975, Congenital cutaneous candidiasi, Am J Dis Child, 129, 1215
  28. Results of the Endophthalmitis Vitrectomy Study: a randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis, 1995, Endophthalmitis Vitrectomy Study Grou, Arch Ophthalmol, 113, 1479
  29. Goldman, 2002, Randomized study of long-term chronic suppressive fluconazole vs. episodic fluconazole for patients with advanced HIV infection and a history of oropharyngeal candidiasis [abstract M-1241]. ACTG 323 and MSG 40 Study Grou
  30. Sobel, 2002, Management of recurrent vulvovaginal candidiasis with maintenance suppressive weekly fluconazole: a multicenter study [abstract LB-8
  31. Karchmer, 2002, Invasive fungal infections in liver transplant recipients considered at low risk [abstract 16
  32. Linden, 1996, Low-dose amphotericin B for the prophylaxis of serious Candida infections in high-risk liver recipients [abstract J47
  33. Grossi, 2000, Prevalence and outcome of invasive fungal infections in 1963 thoracic organ transplant recipients—a multicenter retrospective stud, Transplantation, 70, 112

Cited by

Sorted by citations

Related

Authors
Pappas, P. G., Rex, J. H., Sobel, J. D., Filler, S. G., Dismukes, W. E., Walsh, T. J., & Edwards, J. E.
Affiliations
  • University of Alabama at Birmingham (US)
  • AstraZeneca (United Kingdom) (GB)
  • Wayne State University (US)
  • University of California, Los Angeles (US)
  • National Institutes of Health (US)
ORCID
Venue
Clinical Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2004-01-15
Volume
38
Issue
2
Pages
161-189
ISSN
  • 1058-4838 (ISSN-L)
  • 1537-6591
DOI
10.1086/380796
OpenAlex
W2144495358
Semantic Scholar
0763f09361b8f9df9bd21f5385f453e6bf98a901
Cited by
1,440
References
324
Citations by year
2026: 8 · 2025: 9 · 2024: 21 · 2023: 22 · 2022: 29 · 2021: 27 · 2020: 29 · 2019: 35 · 2018: 33 · 2017: 36 · 2016: 37 · 2015: 43 · 2014: 42 · 2013: 46 · 2012: 58
FWCI
99.02
Type
journal article
Language
en
Open access
Locations
  • Clinical Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
Keywords
candidiasis, invasive candidiasis, antifungal therapy, antifungal prophylaxis, neutropenia, bone marrow transplant recipients, solid organ transplant recipients, antifungal resistance, treatment guidelines
MeSH terms
Antifungal Agents, Candida, Candidiasis, Humans, Microbial Sensitivity Tests

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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