Timing for Step-Down Therapy of Candidemia in Non-Neutropenic Patients: An International Multi-Center Study.

BACKGROUND: Candida bloodstream infection (BSI) remains one of the leading causes of BSI in critically ill and immunosuppressed cancer patients. In light of the changing epidemiology and rising resistant species, duration of treatment and appropriate timing of stepdown therapy from intravenous (IV) to oral antifungal agents are crucial for utmost disease control and overall survival. METHOD: We performed a multicenter retrospective study, with 119 non-neutropenic patients enrolled from four different medical institutions in Brazil, Lebanon, Spain and the United States, to assess the duration of IV therapy and appropriate time to step-down to oral therapy in adult patients, 14 years of age and older, with documented candidemia. The analysis was done using the statistical program R and SAS v9.4. Descriptive statistics are presented as frequencies and tables and the Fisher exact test was used to test the association between the categorical variables: organism, cancer, country, antifungal drug and duration of therapy, and time of step-down. RESULTS: Candida albicans contributed to 45% of bloodstream infection versus 55% of infection caused by Candida non-albicans. The three most common Candida non-albicans are: Candida glabrata 24%, Candida parapsilosis 13% and Candida tropicalis 8%. Most (57%) of the patients were admitted to ICU, whereas 52% had underlying malignancy. Multivariate analysis showed that a stay at ICU or an underlying cancer requiring chemotherapy were independently associated with failure and death (p <0.001). The average total duration of therapy was 14 days in all patients and 16 days in those who responded and survived. Forty-five patients were stepped down to either fluconazole and/or voriconazole in association with clinical and microbiologic resolution of the candidemia. The average (and median) day of step-down was 5 days. Patients who had a stepdown had more favorable outcomes (78% survival) as compared to those with no stepdown (56% survival) (P = 0.022). However, the 20 patients who received 1-4 days of first IV treatment before a stepdown to oral azoles had a comparable outcome (20% mortality) to the 25 patients who received >5 days of treatment (24% mortality - p = 0.75). CONCLUSION: Our data support the IDSA guidelines in that the total duration of treatment for candidemia should be at least 14 days after a negative blood culture. However, in non-neutropenic cancer patients with candidemia, a step-down to oral azole therapy can safely take place early (within 4 days of initiating IV therapy) as long as the patient had clinical and microbiologic resolution of the bloodstream infections.

Treating invasive aspergillosis in patients with hematologic malignancy: diagnostic-driven approach versus empiric therapies.

BACKGROUND: Early antifungal therapy for invasive aspergillosis (IA) has been associated with improved outcome. Traditionally, of empiric antifungal therapy has been used for clinically suspected IA. We compared outcomes of patients with hematologic malignancy and IA who were treated with voriconazole using the diagnostic driven DDA (DDA-Vori) that includes galactomannan testing vs. empiric therapy with a non-voriconazole-containing regimen (EMP-non-Vori) or empiric therapy with voriconazole (EMP-Vori). METHODS: We retrospectively reviewed the medical records of 342 hematologic malignancy patients diagnosed with proven, or probable IA between July 1993 and February 2016 at our medical center who received at least 7 days of DDA-Vori, EMP-Vori, or EMP-non-Vori. Outcome assessment included response to therapy (clinical and radiographic), all-cause mortality, and IA-attributable mortality. RESULTS: By multivariate analysis, factors predictive of a favorable response included localized/sinus IA vs. disseminated/pulmonary IA (p <  0.0001), not receiving white blood cell transfusion (p <  0.01), and DDA-Vori vs. EMP-non-Vori (p < 0.0001). In contrast, predictors of mortality within 6 weeks of initiating IA therapy included disseminated/pulmonary infection vs. localized/sinus IA (p < 0.01), not undergoing stem cell transplantation within 1 year before IA (p = 0.01), and EMP-non-Vori vs. DDA-Vori (p < 0.001). CONCLUSIONS: DDA-Vori was associated with better outcome (response and survival) compared with EMP-non-Vori and with equivalent outcome to EMP-Vori in hematologic malignancy patients. These outcomes associated with the implementation of DDA could lead to a reduction in the unnecessary costs and adverse events associated with the widespread use of empiric therapy.

Emerging outbreaks associated with conflict and failing healthcare systems in the Middle East.

The escalating conflicts in the Middle East have been associated with the rapid collapse of the existing healthcare systems in affected countries. As millions of refugees flee their countries, they become vulnerable and exposed to communicable diseases that easily grow into epidemic crises. Here, we describe infectious disease epidemics that have been associated with conflicts in the Middle East, including cholera, poliomyelitis, measles, cutaneous leishmaniasis, and diphtheria, that call for appropriate preventive measures. Local ongoing wars and failing healthcare systems have resulted in regional and global health threats that warrant international medical interventions.

Appropriate Duration of Intravenous Treatment of Candidemia and Timing of Step Down to Oral Therapy in Non-neutropenic Patients.

In this review, we have analyzed the available literature pertaining to the total duration of intravenous (IV) therapy and the appropriate timing of step down to oral therapy in the management of candidemia. Overview of the guidelines and literature seem to indicate that a minimum of 14 days of antifungal therapy is required in the treatment of candidemia without deeply seated infection. However, this was never based on evidence. Furthermore, step down to oral therapy seems to be dependent on the clinical stability criteria of the patient with candidemia after 4 to 7 days of IV therapy. Further studies are required to evaluate the appropriate total duration of IV therapy, appropriate timing of step down to oral therapy and to validate the clinical criteria that would allow the switch to happen.