Invasive fungal infections are a major cause of morbidity and mortality in patients with prolonged neutropenia and in allogeneic hematopoietic stem cell transplant recipients. The degree and duration of neutropenia influence the risk of opportunistic fungal infections. Because Candida and Aspergillus species are the major causes of invasive fungal infections in neutropenic patients, the fungal section of the NCCN guidelines focus on these two pathogens. Effective prevention and therapy of invasive fungal pathogens is a priority in highly immunocompromised patients with cancer. Three strategies in preventing and treating patients at high risk for fungal infection will be considered: (1) prophylaxis; (2) empirical therapy; and (3) treatment for probable or proven fungal infection. In addition to more effective antifungal agents, growing interest has been noted in novel non-culture detection methods to facilitate early diagnosis of invasive fungal infections.
Thomas A. Cumbo and Brahm H. Segal
Brahm H. Segal and Alison G. Freifeld
Patients with cancer and chemotherapy-induced neutropenia are at risk for severe bacterial infections. This risk is not uniform among all cancer patients but is dependent primarily on the depth and duration of neutropenia and the type of underlying disease. Accordingly, the decision whether to use antibacterial prophylaxis to prevent serious infections in these patients requires a balance between expected benefit and the risks for infection, adverse drug-related events, and emergence of antibiotic resistance. Although antibacterial prophylaxis has the potential to benefit all patients with chemotherapy-induced neutropenia, the benefit regarding reduction in documented infections has been firmly established only in patients with neutropenia expected to exceed 7 days. A recent meta-analysis showed enhanced survival in patients receiving antibacterial prophylaxis during neutropenia; most patients enrolled in the analyzed trials had a hematologic malignancy. Among patients with neutropenia at lower risk for infectious complications (a category that includes most patients with solid tumor malignancies), the main benefit of antibacterial prophylaxis relates to a reduction in fever rather than documented infections. The authors advise quinolone prophylaxis (levofloxacin is preferred), in patients with an expected duration of neutropenia (absolute neutrophil count < 1000/μL) of more than 7 days. Trimethoprim-sulfamethoxazole should be used in patients at risk for Pneumocystis jiroveci (formerly P carinii), such as childhood acute lymphoblastic leukemia. In patients with neutropenia expected to last 7 days or less and not receiving immunosuppressive regimens (e.g., systemic corticosteroids), the authors recommend no initial prophylaxis. However, if such patients develop fever during neutropenia, they should be considered for outpatient empiric therapy with an oral quinolone–containing regimen if they meet criteria for low risk for complications.
Antonio V. Gonzalez, Andrew J. Ullmann, Nikolaos G. Almyroudis and Brahm H. Segal
Invasive fungal infections (IFIs) are a leading cause of infection-related mortality in patients with acute leukemia and prolonged neutropenia and in allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD). Although invasive candidiasis was the principal IFI predating fluconazole prophylaxis, invasive aspergillosis and other mold infections now cause most deaths from fungal infection in this patient population. The availability of broad-spectrum antifungal agents that can be safely administered over prolonged periods has stimulated interest in using mold-active prophylactic agents early as prophylaxis rather than later as therapy for suspected or documented IFIs. Two recent, prospective, randomized trials have shown a clear benefit of posaconazole prophylaxis in patients with myelodysplastic syndrome and acute mye-logenous leukemia with prolonged neutropenia and in allogeneic HSCT recipients with severe GVHD. In contrast, the peer-reviewed published database on the strategy of preemptive antifungal therapy, in which yeast-active prophylaxis (fluconazole) or no antifungal prophylaxis is used initially and modifications are triggered by a combination of laboratory markers and chest CT scans, is currently limited to an open-label feasibility study. Does sufficient evidence currently exist that the net benefit of the preemptive approach is at least on a par with posaconazole prophylaxis in the specific patient groups that were studied? The authors believe not and that more research is needed before the pre-emptive strategy can be recommended.