Invasive aspergillosis

Shortly after the introduction of CT scanning of the thorax, von Eiff and colleagues showed in leukaemia patients, that initiation of antifungal treatment within the first 10 days of infection reduced mortality from 90% to 40% (von Eiff et al). Older data are consistent with this (Aisner et al). A pioneering approach in Dijon, France (Caillot et al) in the 1990's using several diagnostic tests simultaneously, but triggered by regular chest CT scans, reduced mortality by about 40%, as shown in the Kaplan-Meier plot (Figure 1) below:

Figure 1 :

Thus early diagnosis of invasive aspergillosis is highly desirable. Prophylaxis is not possible in many patient groups, many of whom are susceptible to invasive aspergillosis, including:

  • Allogeneic and autologous stem cell transplants
  • Solid organ transplants, especially lung transplant recipients
  • Chronic granulomatous disease sufferers
  • Corticosteroid treated patients including SLE, Wegener's and other renal patients, COPD patients and many others
  • HIV and AIDS patients
  • Liver failure patients
  • Those receiving alpha TNF inhibitors
  • Medical ICU patients

Candidaemia and invasive candidiasis

Candidaemia is expensive in human and financial terms. It has an overall mortality of ~40%, and in many cases results in prolonged ICU and/or high dependency stays, an additional 14.7-36.3 days in a UK study (Hobson, unpublished). In a recent US study of both adults and children with candidaemia, candidaemia resulted in an additional 10% mortality in children, a mean increase length of stay of 21.1 days, and mean increase in hospital charges of $92,266 (Zaoutis et al). For adults the respective figures were 14.5% increase in mortality, 10.1 mean increase in hospital stay and additional charges of $39,331. Treatment is usually given for 3 weeks, if the patient survives long enough. Complications occur in ~15% of cases including endophthalmitis, osteomyelitis and endocarditis, all troublesome and costly conditions to manage.

The diagnosis is usually made by blood culture, sometimes by culture from other sites. If positive at all, blood cultures are usually positive in 2 days (85%). Two recent studies from the US suggest a distinct advantage in survival if treatment is given immediately the diagnosis is considered (Morell et al; Garey et al). These are summarised in table 1.

Table 1 :

Mortality rate from time of blood draw that later turns positive for Candida spp
  Rx in <12 hrs Rx in 12-24 hrs Rx in 24-48 hrs Rx >48 hrs Rx >72 hrs
Morell, 2005 11.1% 30% 32.6% 34.5% -
Garey, 2006 15.4% 23.7% 36.4% 41.4%

These data suggest that if the diagnosis could be made even faster, perhaps one or 2 days earlier by a molecular test, then all the patients would effectively fall into the <12 hours group, with a reduction in mortality of ~20%.


Aisner J, Wiernik PH, Schimpff SC. Treatment of invasive aspergillosis: relation of early diagnosis and treatment to response. Ann Intern Med 1977;86:539-43.

Caillot D, Casasnovas O, Bernard A, Couaillier JF, Durand C, Cuisenier B, Solary E, Piard F, Petrella T, Bonnin A, Couillault G, Dumas M, Guy H. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery.J Clin Oncol. 1997 Jan;15(1):139-47.

Garey KW, Rege M, Pai MP, Mingo DE , Suda KJ, Turpin RS, Bearden DT. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis. 2006;43:25-31.

Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 2005;49:3640-5.

von Eiff M, Roos N, Schulten R, Hesse M, Zuhlsdorf M, van de Loo J. Pulmonary aspergillosis: early diagnosis improves survival. Respiration 1995;62:341-7.

Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States : a propensity analysis. Clin Infect Dis 2005;41:1232-9.