Honar Cherif

The admission of patients with hematological disorders to the intensive care unit (ICU) involves a complex resource usage and may be associated with high mortality. The decision making to transfer a severely ill patient to the ICU, therefore, presents an ethical dilemma. We assessed both early and long-term outcomes in relation to clinical characteristics with the aim to facilitate clinical decision making. We performed a cohort study of hematological patients admitted to ICU at a university hospital. During a 6-year period (1996–2001), 85 patients with a median age of 59 years were admitted to ICU. The majority of patients (88%) suffered from hematological malignancies. Major reasons for ICU admission were respiratory failure (41%) and septic shock/pre-shock (24%). The median duration of ICU admission was 2 (1–67) days. Crude in-ICU, 30-day, and 6-month mortality rates were 30, 49, and 62%, respectively. Overall 5-year survival rate was 20%, and 13 (15%) patients were alive at time of follow-up (median 7.4 years). Respiratory failure requiring ventilatory support and a high Acute Physiology and Chronic Health Evaluation II score was significantly correlated to high in-ICU mortality, but not to long-term outcome. Type of hematological malignancy, neutropenia, thrombocytopenia, bacteremia, prior administration of chemotherapy, age, or gender was not significantly associated with outcome. The current study provides encouraging results on long-term post-ICU outcome also in elderly patients with hematological diseases. For a substantial proportion of critically ill hematological patients, a short time care at an ICU is lifesaving. These patients should be offered intensive care unless or until it is clear that there is little prospect of recovery from the acute illness or that the underlying malignancy cannot be controlled.

Historically, treatment of invasive fungal infections (IFI) has consisted of amphotericin B. However, new therapeutic agents have recently been introduced. At the same time, the relatively low incidence of IFI and the progress in the diagnostic accuracy of IFI have made routine use of empirical antifungal therapy questionable. With the aim to define the present trends in the use of antifungal agents for the treatment of IFI, we prospectively observed type, safety, and efficacy of given antifungal treatment in patients with hematological malignancies during a recent 18-month period. We also analyzed the impact of restricted use of empirical antifungal therapy on IFI-related mortality. A total of 279 episodes of neutropenia and fever following the chemotherapy were recorded. Treatment of IFI was given during the management of 41 (14%) episodes. Voriconazole (27 episodes) and caspofungin (14 episodes) were the only antifungal agents used as initial therapy. The rate of antifungal therapy success outcome was 78%. The overall 4-week mortality rate was 8%. Two patients died of invasive pulmonary aspergillosis. Empirical antifungal therapy was given in 13 episodes with persistent febrile neutropenia (PFN) and resulted in successful outcome in 92% of cases. In general, antifungal agents were well tolerated and only two patients had to discontinue treatment because of severe adverse event. In 127 episodes of PFN, antifungal therapy was deemed unnecessary and accordingly was not administered. In this subgroup of patients, no IFI-related mortality occurred. A better tolerability and efficacy of voriconazole and caspofungin together with the availability of an oral formulation of voriconazole most probably contributed to the observed shift in the use of antifungal agents. A restricted use of empirical antifungal therapy was, in this setting, not associated with an increased IFI-related mortality.

It is now evident that patients experiencing febrile neutropenia induced by chemotherapy do not constitute a homogeneous group. With increasing accuracy it is now possible to identify low-risk patients for whom less intensive and more convenient treatment may be appropriate. In a cohort of such patients with hematologic malignancies, we prospectively validated the usefulness of the risk-index of the Multinational Association of Supportive Care in Cancer (MASCC) in identifying patients at low risk for the development of serious medical complications. Moreover, we studied the feasibility and safety of early discharge of these low-risk patients 24 hours after fever defervescence with subsequent oral antibiotic therapy. Of the 279 episodes of febrile neutropenia included, 105 (38%) had a MASCC risk-index score indicating low risk. Serious complications were reported in connection with 111 (63%) high-risk and 16 (15%) low-risk episodes (p<0.0001). The risk-index identified low-risk patients with a specificity, sensitivity and positive predictive value of 87%, 58%, and 84%, respectively. A substantial proportion of the low-risk patients (36%) were considered ineligible for oral therapy, while the remaining 67 (64%) received oral antibiotic treatment following discharge from the hospital 24 hours after defervescence. Upon final evaluation, 64 of the discharged patients (95%) remained afebrile, only three required readmission and there was no mortality in this group. The MASCC risk-index is a valuable tool for identifying febrile neutropenic patients at low risk for complications. Oral antibiotic treatment following discharge from the hospital 24 hours after defervescence offers a safe and cost-effective alternative to the conventional management of carefully selected low-risk patients.

The species distribution and antifungal susceptibility of yeasts isolated from colonization cultures, and the contribution of previous fluconazole prophylaxis to the emergence of resistance, was prospectively studied in 87 neutropenic patients treated for haematological malignancies. Minimal inhibition concentrations (MICs) to fluconazole, itraconazole and voriconazole for 123 yeast isolates (65 Candida albicans, 22 Candida glabrata, 15 Saccharomyces cerevisiae, 5 Candida krusei, 5 Candida norvegensis, 11 other Candida spp.) were determined by E-test. Fluconazole MICs for Candida species and S. cerevisiae isolated from patients given prophylaxis were > or =2 mg/l in 24 of 40 (60%) isolates compared with 26 of 83 (31%) isolates from patients in the non-prophylaxis group (p =0.002). Among the non-albicans yeast species reduced susceptibility was common against itraconazole but was rarely found against voriconazole. Cross resistance between fluconazole and itraconazole was observed in 14 of all isolates, 4 of them also showing reduced susceptibility to voriconazole (MICs 4-8 mg/l). Fluconazole prophylaxis may contribute to emergence of less susceptible yeast strains also in patients with haematological malignancies not treated with allogeneic bone marrow transplantation.