Treatment of invasive candidiasis with caspofungin in the intensive care unit

Background

Invasive candidiasis (IC) is increasingly recognized as an important complication of intensive care, and yet remains difficult to diagnose. Standard therapies have included amphotericin B (AmB), despite concerns about its toxicity, or fluconazole, even though some non-albicans Candida species may be azole-resistant. Caspofungin (CAS) is a novel, generally well-tolerated antifungal drug with fungicidal activity against both C. albicans and non-albicans Candida species. We retrospectively examined the demographics, risk factors, baseline characteristics, and outcomes of patients initially treated in an intensive care unit (ICU) enrolled in a randomized study of CAS vs AmB for IC.

Methods

Adults with symptoms or signs of IC and positive cultures for Candida from blood and/or another normally sterile site were eligible for participation in a double-blind, randomized trial comparing CAS (50 mg/day after a 70 mg/day loading dose) with AmB (0.6–1.0 mg/kg per day). Antifungal therapy was to be continued for 14 days after the last positive Candida culture, but could be completed with oral fluconazole after 10 days of intravenous (IV) study drug. A favorable outcome required complete resolution of symptoms and eradication of Candida pathogen(s). We have retrospectively analyzed results from all patients who received their first dose of study drug while in the ICU. All treated patients with a confirmed diagnosis were included in the modified intention-to-treat (MITT) analysis at the completion of IV study therapy; missing assessments were counted as unfavorable. Mortality rates include death due to any cause from the initiation of the study through the 6–8 weeks following completion of IV therapy. Relapse rates represent documented relapses in the 6–8 weeks after completion of IV therapy in those patients who achieved a favorable response at the completion of IV study therapy.

Results

Ninety-seven (43%) of the 224 MITT patients received their first dose of study drug in an ICU, including 40/109 (37%) of the CAS-treated patients and 57/115 (50%) of the AmB-treated patients (P = 0.06). Medians (range) for age and APACHE II score were 59 (17–84) and 17 (6–36). Investigator-specified risk factors present in > 20% of patients were: broad-spectrum antibiotics (92%), central venous catheters (84%), recent surgery (70%), hyperalimentation (47%), and underlying cancer (22%). Eighty-one percent of the ICU patients were candidemic, including three who also had pleural or peritoneal candidiasis. Among the ICU patients, there were no differences between the two treatment arms with regard to age, APACHE II scores, risk factors, or site of Candida infection. ICU and non-ICU patients had comparable baseline characteristics, except for lower APACHE scores (13; 0–28) and less frequent surgery (35%) in the non-ICU group. Favorable response, relapse, and mortality rates were as presented in Table 1.

Table 1 :

Conclusions

In this post hoc subgroup analysis, the efficacy of CAS was similar to AmB for IC in patients whose treatment was initiated in the ICU. CAS provides another therapeutic option for seriously ill patients with documented IC.