Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Comparison of β-D-Glucan Surveillance With Preemptive Anidulafungin Versus Standard Care for the Management of Invasive Candidiasis in Surgical Intensive Care Unit Patients
Brief Summary: This is a single center, prospective, open label assessment of β-D-glucan surveillance with preemptive anidulafungin therapy versus standard care for the prevention of invasive candidiasis in at-risk surgical intensive care unit (SICU) patients. Subjects will be stratified by APACHE II score and randomized in 3:1 fashion to either biweekly surveillance using the β-D-glucan assay or standard care. Subjects in the active monitoring arm will receive intravenous anidulafungin should the β-D-glucan exceed 60 pg/mL on a single determination. Subjects in the standard care arm will have biweekly blood draws for β-D-glucan, but the specimens will be batched and tested retrospectively. Antifungal use in the standard care arm is at the discretion of the treating physicians. The primary study end-points are the feasibility of a preemptive antifungal strategy in a SICU setting, β-D-glucan test characteristics, and the safety and tolerability of preemptive anidulafungin. Risks associated with study participation include the risks associated with blood draws, study drug related side effects, and the potential for loss of confidentiality.


Options:
A: Inclusion Criteria:

1. Adult patients (\>18 years old)
2. In the ICU \> 48 hours
3. Mechanically ventilated (\>48 hours)
4. Grow a Candida spp. on respiratory tract secretion culture (either by Bronchoalveolar Lavage or Endotracheal Aspirate) taken on or between 48 hours before or after the day of their suspicion of respiratory tract infection.
5. Develop a clinical suspicion of respiratory tract infection while ventilated as defined by the following criteria (as defined previously in our VAP trial)5:

   * The presence of new, worsening or persistent radiographic features suggestive of pneumonia without another obvious cause AND
   * The presence of any two of the following:

     * Fever \> 38C (core temperature)
     * Leukocytosis (\>11.0 x109/L) or neutropenia (\<3.5 x109/L)
     * Purulent endotracheal aspirates or change in character of aspirates
     * Isolation of pathogenic bacteria from endotracheal aspirates
     * Increasing oxygen requirements

Exclusion Criteria:

1. Patients not expected to be in ICU for more than 72 hours (due to imminent death, withdrawal of aggressive care or discharge).
2. Patients with Candida spp. in the blood or another sterile body site.
3. Patients colonized at other non-pulmonary body site(s) with Candida.
4. Already being treated with antifungal drugs (because of documented fungal infection, pre-emptive therapy, or prophylaxis).
5. Allergy to study drugs (Fluconazole or the Echinocandin on formulary at treating institution).
6. Immunocompromised patients (post-organ transplantation, Acquired Immunodeficiency Syndrome \[AIDS\], neutropenia \[\<1000 absolute neutrophils\], corticosteroids \[\>20 mgs/day of prednisone or equivalent for more than 6 months\]). These patients are excluded since Candida may be more invasive and these patients are much more likely to require systemic antifungal therapy.
7. Patients with fulminant liver failure or end stage liver disease (Child's Class C).
8. Women who are pregnant or lactating.
9. Enrollment in industry sponsored interventional trial (co-enrollment in other academic studies would be allowed with the proviso that there was no potential interaction between the protocols).
10. Prior randomization in this study.
B: Inclusion Criteria:

* Age ≥18 years
* Admission to the intensive care unit for ≥ 72 hours and expected to stay an additional 48 hours
* IV access for administration of study drug
* Subject (or subject's legal representative) able to give written informed consent

Exclusion Criteria:

* History of hypersensitivity or intolerance to echinocandin antifungals
* Liver function test (ALT, AST (aspartate aminotransferase), and/or total bilirubin) greater than 10 times the upper limits of normal (ULN)
* Pregnant or lactating women
* Treatment with systemic antifungal therapy within the preceding 7 days
* Documented invasive fungal infection at baseline/screening
* Life expectancy less than 2 days or moribund
C: Inclusion Criteria:

* Non-pregnant \>18 yrs of age
* Subjects admitted to ICU during the preceding 3 days and expected to stay in the ICU for at least another 48 hours.Subjects can be enrolled on days 3-5 of ICU admission.
* Subjects meeting the clinical prediction rule

Exclusion Criteria:

* Subjects with an allergy/intolerance to caspofungin or echinocandin analog
* absolute neutrophil count \<500/mm3 at study entry or likely to develop such a count during therapy
* acquired immunodeficiency syndrome, aplastic anemia or chronic granulomatous disease
* moderate or severe hepatic insufficiency
* subjects who are pregnant or lactating
* unlikely to survive \< 24 hours
* subjects who have received systemic antifungal therapy within 10 days prior to study entry
* Documented active proven or probable invasive fungal infection upon enrollment
* previously enrolled in this study
* Currently on another investigational agent or have received an investigational agent within 10 days prior to study entry.
D: Inclusion Criteria:

* surgical patients admitted to our ICU older than 18 years of age and expected to require invasive mechanical ventilation for more than 48 h.

Exclusion Criteria:

* pregnancy,
* proven Candida infection,
* prophylactic or curative antifungal treatment within the last 2 months,
* contraindication to oral drug administration,
* known allergy to nystatin or its derivatives, and prior inclusion in the study

Answer: B