Because invasive aspergillosis is a devastating infection for severely immunocompromised patients, it is critical that treatment be started early.29 The majority of cases of invasive aspergillosis are initially treated with only a presumptive diagnosis.53 However, it is important that even after the start of antifungal treatment, a definite diagnosis be pursued vigorously to exclude infection with other pathogens. A questionable diagnosis will nurture uncertainty about the best possible therapeutic strategy, particularly if the patient is not responding optimally, or if serious adverse events occur. Establishing a definite diagnosis also has crucial implications for long-term treatment of the suspected infection, as well as for management of the underlying disease.
When invasive aspergillosis is suspected or confirmed, AmB should be given intravenously in a dose of 1 to 1.5 mg/kg/day.29, 53,115 In HSCT patients, who almost always are treated with other nephrotoxic agents, a lipid formulation of AmB, usually given at a dosage of 5 mg/kg/day, should be considered as first-line therapy.
Information concerning efficacy and safety of lipid formulations of AmB in aspergillosis comes mainly from open-label emergency-use protocols.120, 123-125, 132, 133 In a multicenter trial, patients who had proven or probable aspergillosis and who were treated with ABCD were compared retrospectively with patients treated with conventional AmB.134 Response and survival rates among ABCD-treated patients were higher than among those treated with conventional AmB (49% versus 23%, and 50% versus 28%, respectively). A multicenter randomized trial comparing L-AmB with conventional AmB in the treatment of neutropenic patients with either documented invasive mycosis or suspected invasive pulmonary aspergillosis has reported superior efficacy and safety for L-AmB.135 Data for the subgroup of patients with documented infections showed overall mortality rates of 38% for AmB versus 22% for L-AmB.
Voriconazole has shown superior results when compared with conventional AmB for treatment of invasive aspergillosis in an open randomized trial consisting primarily of HSCT recipients and patients with hematologic malignancies.136
Caspofungin has shown efficacy and safety in patients with documented invasive aspergillosis who were unresponsive to or intolerant of prior antifungal therapy.137 Overall, 41% (22 of 54) of patients receiving caspofungin responded favorably to treatment. The response rate for patients who were refractory to other therapy was 34% (15 of 44) versus 70% (7 of 10) for those who were intolerant of other therapy.
G-CSF and GM-CSF have been used adjunctively with antifungal agents to treat aspergillosis. As an additional approach, G-CSF has been used to pretreat healthy donors in order to harvest high numbers of neutrophils that can be given to patients with therapy-refractory invasive mycoses. No controlled trials have assessed the effectiveness of this adjunctive therapy.
Surgery is indicated if localization of the lesions poses a direct threat of invasion of a major vessel with the risk of fatal hemorrhage, or for excision of localized infection after a period of antifungal therapy.53,115,138 Most surgeons reserve elective lung resection for patients with a single or limited number of persisting shadows confined to one lobe who have to undergo subsequent HSCT or more aggressive chemotherapy.
It is essential to see a clinical and radiologic response before therapy is discontinued. Many severely immunocompromised patients require a longer duration of therapy than length of hospitalization. For these cases, treatment with oral itraconazole or voriconazole after they have responded to AmB is an option.53,139,140 Absorption of voriconazole is superior to that of itraconazole and is the preferred agent. Any patient with prior aspergillosis should receive antifungal therapy when the next course of chemotherapy commences. Such secondary prophylaxis has been shown to prevent recrudescence in the majority of patients.141-143
Course Number: V035D
This CME Expires on July 1, 2005; no tests will be accepted after this date.
This course is accredited by
The University of Pittsburgh School of Medicine, Center for Continuing Education
and The International Immunocompromised Host Society