akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

侵襲性カンジダ

侵襲性カンジダカンジダ血症

薬剤師の関わりが重要だと思います。
死亡率高く、遭遇することもしばしばです。

外れたマネジメントを避けたい疾患です。特に、CRBSIは、外せません。

抗真菌薬、眼科コンサル、血培陰性までの毎日血培などなど…

それでは、UpToDateを引用し復習

For nonneutropenic and neutropenic patients with candidemia, we recommend an echinocandin rather than fluconazole or amphotericin B (Grade 1B).

●The echinocandins are administered intravenously as follows:
  • Caspofungin is given at an initial dose of 70 mg on the first day of treatment, followed by 50 mg daily; dose reduction is required with hepatic dysfunction.
  • Anidulafungin is given at an initial dose of 200 mg on the first day, followed by 100 mg daily.
  • Micafungin is given at a dose of 100 mg daily for candidemia; no loading dose is needed.
●Nonneutropenic and neutropenic patients who are clinically stable, who have Candida isolates that are susceptible to fluconazole, and who have negative repeat blood cultures can be transitioned to oral fluconazole after five to seven days. For most Candida species, fluconazole should be given at a dose of 400 mg (6 mg/kg) orally once daily for step-down therapy.

Blood cultures should be checked daily or every other day after initiating antifungal therapy until they become negative

●All patients who have candidemia, whether or not they have ocular symptoms, should undergo an ophthalmologic examination by an ophthalmologist to look for evidence of endophthalmitis.

●In the patient with candidemia alone, treatment should be continued for 14 days after blood cultures have yielded no yeast. In addition, all patients should have resolution of symptoms attributable to candidemia and resolution of neutropenia before antifungal therapy is discontinued. Patients with candidemia and metastatic foci of infection (eg, eye, bone, heart, liver, spleen) require a longer duration of therapy.

●Central venous catheters (CVCs) should be removed from most patients with candidemia as soon as possible. In patients in whom candidemia is likely to come from the gastrointestinal tract in the setting of chemotherapy-induced mucositis, removal should be considered, acknowledging the risks of CVC removal in the setting of thrombocytopenia (which is common in such patients). Some clinicians will attempt to retain the catheter in these patients.

Empiric antifungal therapy recommendations in patients with neutropenic fever and antifungal prophylaxis in neutropenic patients are discussed in detail elsewhere.

f:id:akinohanayuki:20160131103905j:image


次に、IDSAガイドライン から 少しだけ抜粋。
無料なので全文は元ファイルを確認ください。
噂のevidence概念図は、私もまだしっくりきません。


Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America


I. What Is the Treatment for Candidemia in Nonneutropenic Patients?

Recommendations

1. An echinocandin (caspofungin: loading dose 70 mg, then 50 mg daily; micafungin: 100 mg daily; anidulafungin: loading dose 200 mg, then 100 mg daily) is recommended as initial therapy (strong recommendation; high-quality evidence).

2. Fluconazole, intravenous or oral, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily is an acceptable alternative to an echinocandin as initial therapy in selected patients, including those who are not critically ill and who are considered unlikely to have a fluconazole-resistant Candida species (strong recommendation; high-quality evidence).

3. Testing for azole susceptibility is recommended for all bloodstream and other clinically relevant Candida isolates. Testing for echinocandin susceptibility should be considered in patients who have had prior treatment with an echinocandin and among those who have infection with C. glabrata or C. parapsilosis (strong recommendation; low-quality evidence).

4. Transition from an echinocandin to fluconazole (usually within 5–7 days) is recommended for patients who are clinically stable, have isolates that are susceptible to fluconazole (eg, C. albicans), and have negative repeat blood cultures following initiation of antifungal therapy (strong recommendation; moderate-quality evidence).

5. For infection due to C. glabrata, transition to higher-dose fluconazole 800 mg (12 mg/kg) daily or voriconazole 200–300 (3–4 mg/kg) twice daily should only be considered among patients with fluconazole-susceptible or voriconazole-susceptible isolates (strong recommendation; low-quality evidence).

6. Lipid formulation amphotericin B (AmB) (3–5 mg/kg daily) is a reasonable alternative if there is intolerance, limited availability, or resistance to other antifungal agents (strong recommendation; high-quality evidence).

7. Transition from AmB to fluconazole is recommended after 5–7 days among patients who have isolates that are susceptible to fluconazole, who are clinically stable, and in whom repeat cultures on antifungal therapy are negative (strong recommendation; high-quality evidence).

8. Among patients with suspected azole- and echinocandin-resistant Candida infections, lipid formulation AmB (3–5 mg/kg daily) is recommended (strong recommendation; low-quality evidence).

9. Voriconazole 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily is effective for candidemia, but offers little advantage over fluconazole as initial therapy (strong recommendation; moderate-quality evidence). Voriconazole is recommended as step-down oral therapy for selected cases of candidemia due to C. krusei (strong recommendation; low-quality evidence).

10. All nonneutropenic patients with candidemia should have a dilated ophthalmological examination, preferably performed by an ophthalmologist, within the first week after diagnosis (strong recommendation; low-quality evidence).

11. Follow-up blood cultures should be performed every day or every other day to establish the time point at which candidemia has been cleared (strong recommendation; low-quality evidence).

12. Recommended duration of therapy for candidemia without obvious metastatic complications is for 2 weeks after documented clearance of Candida species from the bloodstream and resolution of symptoms attributable to candidemia (strong recommendation; moderate-quality evidence).

V. What Is the Role of Empiric Treatment for Suspected Invasive Candidiasis in Nonneutropenic Patients in the Intensive Care Unit?

Recommendations

28. Empiric antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis and no other known cause of fever and should be based on clinical assessment of risk factors, surrogate markers for invasive candidiasis, and/or culture data from nonsterile sites (strong recommendation; moderate-quality evidence). Empiric antifungal therapy should be started as soon as possible in patients who have the above risk factors and who have clinical signs of septic shock (strong recommendation; moderate-quality evidence).

29. Preferred empiric therapy for suspected candidiasis in nonneutropenic patients in the intensive care unit (ICU) is an echinocandin (caspofungin: loading dose of 70 mg, then 50 mg daily; micafungin: 100 mg daily; anidulafungin: loading dose of 200 mg, then 100 mg daily) (strong recommendation; moderate-quality evidence).

30. Fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily, is an acceptable alternative for patients who have had no recent azole exposure and are not colonized with azole-resistant Candida species (strong recommendation; moderate-quality evidence).

31. Lipid formulation AmB, 3–5 mg/kg daily, is an alternative if there is intolerance to other antifungal agents (strong recommendation; low-quality evidence).

32. Recommended duration of empiric therapy for suspected invasive candidiasis in those patients who improve is 2 weeks, the same as for treatment of documented candidemia (weak recommendation; low-quality evidence).

33. For patients who have no clinical response to empiric antifungal therapy at 4–5 days and who do not have subsequent evidence of invasive candidiasis after the start of empiric therapy or have a negative non-culture-based diagnostic assay with a high negative predictive value, consideration should be given to stopping antifungal therapy (strong recommendation; low-quality evidence).


最後に有名なRCT リンクちょこっと貼ります。

N Engl J Med. 1994;331(20):1325.
A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute.

Clin Infect Dis. 1996;23(5):964.
Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature.

Infection. 1996;24(6):426.
A randomized study comparing fluconazole with amphotericin B/5-flucytosine for the treatment of systemic Candida infections in intensive care patients.

Eur J Clin Microbiol Infect Dis. 1997;16(5):337.
Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group.

Intensive Care Med. 2002 Dec;28(12):1708-17. Epub 2002 Nov 1.
Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination.

Clin Infect Dis. 2003;36(10):1221.
A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects.

Lancet. 2007;369(9572):1519.
Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial.

N Engl J Med. 2007;356(24):2472.
Anidulafungin versus fluconazole for invasive candidiasis.

Clin Infect Dis. 2007;45(7):883.
Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis.

Ann Intern Med. 2008;149(2):83.
Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial.

Clin Infect Dis. 2009;48(12):1676.
A Multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis.

BMC Infect. Dis. 2011.:261.
Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcome.

Clin Infect Dis. 2012;54(8):1110.
Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials.

Clin Infect Dis. 2014 May;58(9):1219-26. Epub 2014 Feb 27.
MSG-01: A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting.

Clin Infect Dis. 2015 Dec;61(11):1671-8. Epub 2015 Aug 13.
A Randomized, Placebo-controlled Trial of Preemptive Antifungal Therapy for the Prevention of Invasive Candidiasis Following Gastrointestinal Surgery for Intra-abdominal Infections.