Anti-infective strategies in neutropenia

Abstract

Anti-infective strategies in febrile neutropenic patients have evolved continuously over the past decade. The changing spectrum of not only the infecting organisms but also of the underlying disease have necessitated different approaches. While the duration and degree of neutropenia have remained the most important risk factors for the development of invasive infections, other factors such as the presence of catheters, cytotoxic chemotherapy, mucositis, infection history, microbial colonisation and the concomitant immune dysfunction, also play a major role in the design of the anti-infective strategy. Individualisation of treatment strategy and the need for flexibility in response to local microbial ecology have also become key concepts. Controversy still surrounds the optimal prophylactic and empirical therapeutic regimens. Selective suppression of the endogenous microbial flora, particularly of the alimentary tract and other mucosal surfaces is recommended for high risk patients, such as those with anticipated profound and prolonged neutropenia, severe post chemotherapy mucositis and the presence of long-term intravenous catheters. For all other risk categories, cost benefit ratios must be carefully weighed against potential clinical benefit. Empirical monotherapy with broad-spectrum cephalosporins or a carbapenem is accepted as a cost-effective and usually well tolerated alternative to combination therapy. However, close monitoring of the patient's response is essential. Early empirical antifungal therapy also remains one of the prerequisites for a successful outcome in the management of neutropenic fever. Safer and more effective antifungal agents are urgently needed. In the future haematopoietic growth factors and other new techniques, such as peripheral blood progenitor cell transplantations, are likely to play a role in the early prophylaxis and management of severe neutropenic infective episodes. Future anti-infective strategies in the neutropenic host may not only lie with antibiotics, but also encompass successful modulation of host defences.