Tuesday, January 12, 2016

Updated guidelines for the treatment of candida infections

Published here. The guideline opens with this disclaimer, which acknowledges the first principles of EBM:

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.


Candidemia in nonneutropenic patients

An echinocandin is first choice. Fluconazole is considered an alternative in selected patients, not critically ill and considered unlikely to have resistance. (Note that in candidemia the blood cultures initially come back as showing “yeast” rather than “candida.” Although the guideline doesn't specifically address this real world issue treatment needs to be started without delay at that point).

Concerning susceptibility testing in these patients:

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..

Transition to fluconazole from an ecinocandin is recommended if all the following conditions are met: the patient is clinically stable; the isolates are sensitive to fluconazole on susceptibility testing; repeat blood cultures after initiation of treatment are negative.

Such patients are recommended to have an ophthalmology exam, preferably by an ophthalmologist, within the first week of diagnosis. (This recommended timing for the exam differs from that of neutropenic patients as will be mentioned below. Different types of occular involvement have specific treatment indications including intraoccular injections in some).

Follow up blood cultures are recommend at least every other day until clearance. The duration of treatment, absent metastatic complications, is two weeks post documented blood culture clearance and symptom resolution.

Regarding central venous catheters, form the paper:

Central venous catheters (CVCs) should be removed as early as possible in the course of candidemia when the source is presumed to be the CVC and the catheter can be removed safely; this decision should be individualized for each patient

Candidemia in neutropenic patients

An ecinocandin is recommend as first choice. Lipid based amphotericin, fluconazole and voriconazole are discussed for certain situations as alternatives.

Duration of therapy is essentially the same as in nonneutropenic patients provided the neutropenia has resolved.

The ophthalmologic exam, in contrast to nonneutropenic patients, is deferred until within one week of recovery from neutropenia, since manifestations are minimal during neutropenia.

The recommendation for central venous catheter removal is similar to that for nonneutropenic patients: clinical judgment, with the understanding that non-CVC sources such as the GI tract figure prominently in neutropenic candidemia.

Hepatosplenic candidiasis

Ecinocandins and lipid based amphotericin are recommend with equal strength. Treatment is continued until lesions resolve on imaging, often a matter of several months.

Empiric treatment in critically ill patients when candida is suspected but not confirmed

From the paper:

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).

This seems to me like a low threshold for adding antifungal agents and this is in reference to nonneutropenic patients. Oddly enough neutropenia is not mentioned in this portion of the guideline but I would think an even lower threshold might apply.

Prophylaxis against invasive candidiasis in critically ill patients

Here a low level and somewhat vague recommendation is given:

34. Fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily, could be used in high-risk patients in adult ICUs with a high rate (greater than 5%) of invasive candidiasis (weak recommendation; moderate-quality evidence).

35. An alternative is to give an echinocandin (caspofungin: 70-mg loading dose, then 50 mg daily; anidulafungin: 200-mg loading dose and then 100 mg daily; or micafungin: 100 mg daily) (weak recommendation; low-quality evidence).

Intra-abdominal candidiasis

From the paper:

Empiric antifungal therapy should be considered for patients with clinical evidence of intra-abdominal infection and significant risk factors for candidiasis, including recent abdominal surgery, anastomotic leaks, or necrotizing pancreatitis (strong recommendation; moderate-quality evidence).

Concerning necrotizing pancreatitis most general recommendations are against antimicrobial treatment unless there is evidence of infected necrosis.

Oropharyngeal candidiasis

From the paper:

122. For mild disease, clotrimazole troches, 10 mg 5 times daily, OR miconazole mucoadhesive buccal 50-mg tablet applied to the mucosal surface over the canine fossa once daily for 7–14 days are recommended (strong recommendation; high-quality evidence).

123. Alternatives for mild disease include nystatin suspension (100 000 U/mL) 4–6 mL 4 times daily, OR 1–2 nystatin pastilles (200 000 U each) 4 times daily, for 7–14 days (strong recommendation; moderate-quality evidence).

124. For moderate to severe disease, oral fluconazole, 100–200 mg daily, for 7–14 days is recommended (strong recommendation; high-quality evidence).

Esophageal candidiasis

From the document:

131. Systemic antifungal therapy is always required. A diagnostic trial of antifungal therapy is appropriate before performing an endoscopic examination (strong recommendation; high-quality evidence).

132. Oral fluconazole, 200–400 mg (3–6 mg/kg) daily, for 14–21 days is recommended (strong recommendation; high-quality evidence).

133. For patients who cannot tolerate oral therapy, intravenous fluconazole, 400 mg (6 mg/kg) daily, OR an echinocandin (micafungin, 150 mg daily, caspofungin, 70-mg loading dose, then 50 mg daily, or anidulafungin, 200 mg daily) is recommended (strong recommendation; high-quality evidence).

There is much more in the body of the paper. I have only provided highlights of things I think hospitalists might need for quick reference.

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