Faculty Bibliography

The antifungal activity of echinocandins is concentration dependent. Previously, we demonstrated that high-dose caspofungin (HD-CSP; 100 mg daily) was well tolerated in 34 immunosuppressed patients with cancer and may have favorably influenced outcomes. We retrospectively assessed all 91 patients in whom HD-CSP was given for the treatment of invasive fungal disease (IFD). The median number of doses was 18.5 +/- 21.5, and in 8 (9%) patients more than 40 doses were given. Most (62%) of the patients had leukemia. A total of 45 (49%) patients had undergone stem cell transplantation; 80% received allogeneic grafts and 47% had graft-versus-host disease. High-dose corticosteroids were given during antifungal therapy in 26 (29%) patients. In all, 8 (9%) patients had new elevation in serum bilirubin during HD-CSP therapy; normalization occurred after voriconazole and HD-CSP were discontinued in 4 patients each. No other short-term or delayed adverse events were observed. In all, 40 (44%) patients died of IFD. High-dose corticosteroids during HD-CSP (odds ratio [OR] 8, 95% confidence interval [CI] 2.1-30.4; P < .002) and starting HD-CSP in the critical care unit (OR 67.5, 95% CI 5.25-868.9; P < .001) were associated with death from fungal disease. Prolonged HD-CSP therapy was well tolerated. Drug-induced hyperbilirubinemia may pose a potential limitation for continued HD-CSP use in highly susceptible patients with hematologic neoplasms and stem cell transplantation.

Fidaxomicin was given to treat proven Clostridium difficile infection (CDI) in 20 patients receiving care in critical care units (CCUs) and compared with 30 patients on general medical floors. At baseline, CCU patients had more initial CDI episodes, severe and complicated disease, and concurrent broad-spectrum antibiotic coverage. On multivariate analysis, response of fidaxomicin therapy among critically ill patients was comparable to that among patients in the general medical wards.

Objectives: Accurate diagnosis of infections in transplant recipients remains a daunting task. To address the diagnoses dilemma, we assessed feasibility of procalcitonin (PCT), a recently approved biomarker in patients at a major University Medical Center in New York. Methods: All data was retrieved retrospectively after approval from Institutional Review Board. Transplant recipients were compared with general medicine patients, and patients with hematologic neoplasia and those being cared for in medical and surgical intensive care units between April 2012 and February 2013. Chi-square and Mann Whitney U test were used for statistical analysis. PCT (ng/ml) and other values are given as median [range]. Results: Among 342 patients studied, transplant recipients (n=26) were younger (60 vs. 69 years; p<0.01), had fewer cardiovascular diseases (19.2% vs. 44.3%; P<0.05), whereas diabetes was more common compared with other patients (53.8% vs. 21.8%; P<0.05). APACHE II scores was not different in either group (15 vs. 17; p=0.06). Similarly, there were no differences for corticosteroid use, chemotherapy and surgeries (P>0.05). PCT values were higher in transplant recipients with bacteremia, Gram-negative infections, and pneumonia (Table 1). There were no significant differences in PCT values among recipients of SOT vs. HSCT (1.62 [0.05-197] vs. 0.28 [0.05-13.1], respectively; P=0.3) during early (<1 month) or later transplant period (1.9 [0.05-13.10] vs. 1.15 [0.015-197], respectively; P=0.8). Conclusions: PCT appears as a promising diagnostic tool for transplant recipients with bacteremia, Gram-negative infections and pneumonia. Further validation studies are underway. TABLE 1. Comparison of PCT in transplant and other patients. (Table Presented)

Abstract The T-SPOT.TB test (TS.TB), an interferon-gamma (IFN-gamma) release assay (IGRA), is superior in diagnosing latent tuberculosis infection compared with the conventional tuberculin skin test (TST). However, whether cytotoxic chemotherapy and treatment with new-generation antineoplastic monoclonal antibodies affects the TS.TB is not certain. We evaluated the feasibility of using the TS.TB in this population. Sixteen cancer patients at high risk for tuberculosis exposure were prospectively evaluated with the TST and TS.TB. Blood samples were obtained 7.5 +/- 89.3 days after the most recent cycle of antineoplastic therapy. Six patients (38%) were febrile within 24 h of blood sampling; high-dose corticosteroid therapy and profound treatment-induced neutropenia were present in 1 patient each. In all patients, TS.TB showed no evidence of latent tuberculosis infection. A robust mitogen-induced IFN-gamma response was seen in samples from 14 patients (88%) despite therapy with high-dose corticosteroids, cyclophosphamide, fludarabine, gemtuzumab ozogamicin, and alemtuzumab. The presence of fever or profound neutropenia did not negatively impact mitogen response by peripheral lymphocytes. The 2 patients whose peripheral blood lymphocytes (> 500 cells/ml) failed to generate a cytokine response to ex vivo mitogen stimulation had refractory advanced cancer. Unlike the TST, a negative TS.TB provided interpretable results even in cancer patients undergoing new-generation immunosuppressive therapy.

BACKGROUND/AIMS: Despite limited evidence for efficacy, granulocyte transfusions (GTX) are used to prevent and treat opportunistic infections in patients with neutropenia. METHODS: Three hundred and seventy-three GTX given to 74 patients were assessed retrospectively. RESULTS: GTX were discontinued because of clinical improvement more often in patients with severe infections than in patients without severe infections (27 vs. 12%; p