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Computed Tomography in Febrile Neutropenia

Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

To the Editor: I read with great interest the article by Heussel et al on the use of high-resolution thoracic computed tomography (HRCT) for the diagnosis of subtle pulmonary infiltrates in febrile neutropenic cancer patients with fever and a normal chest x-ray that was published in the March 1999 issue of the Journal of Clinical Oncology.¹ The study is the largest prospective and rigorous analysis of the role of this relatively new, highly sensitive diagnostic technique in the study of febrile neutropenia of unknown origin. I must disagree, however, with the criteria used by the authors for defining Candida pneumonia. This is an important matter, since among the 188 patients, only 48 had a microorganism isolated that was considered to be the cause of the pneumonia, and in 20 cases it was a Candida species isolated from a concurrent bronchoalveolar lavage (BAL). The true-positive cases were thus defined as those with an abnormal HRCT and a relevant micro-organism isolated and/or opacification of a simple chest x-ray during follow-up. Candida pneumonia, however, cannot be diagnosed by the criteria used in this study (> 100,000/mL colonies of Candida species isolated from a BAL sample). Candida pneumonia can occur by two mechanisms, either as hematogenous spread or as primary pneumonia after aspiration of nasopharyngeal secretions.²-⁴ The latter mechanism seems to be the most frequent in patients with cancer.⁴ Roentgenographic findings are nonspecific, and isolation of Candida species from BAL (at any concentration) or sputum is very nonspecific and cannot be used as a diagnostic criterion.²-⁵ True Candida pneumonia is rare, with only 55 well-documented cases reported before 1993.⁴ In another study, among 1,506 bone marrow transplant recipients, 171 (11.6%) developed an invasive candidiasis, but only 18 cases of well-documented Candida pneumonia occurred.⁵ Most investigators believe that the true incidence must be higher, but in patients with cancer and severe pancytopenia, lung biopsies are rarely safely obtainable. Thus, strong research efforts are being invested into new diagnostic techniques that increase the reliability of currently available tests, not only for invasive candidiasis but also for aspergillosis and other pathogens. However, with cultures of BAL samples, as used in the study by Heussel et al,¹ the diagnosis of Candida pneumonia cannot be made, not even a putative diagnosis. These 20 cases would probably best be reclassified as pneumonia of unknown origin. This, of course, would change the statistical data of their study. However, the real interest of this study is the fact that pulmonary lesions can be detected in up to 60% of febrile neutropenic patients with a normal simple chest x-ray, and this is a starting point for developing more specific diagnostic techniques.

REFERENCES

1. Heussel CP, Kauczor HU, Heussel GE, et al: Pneumonia in febrile neutropenic patients and in bone marrow and blood stem-cell transplant recipients: Use of high-resolution computed tomography. J Clin Oncol 17:796-805 1999[Abstract/Free Full Text]

2. Dubois PJ, Myerowitz RL, Allen CM: Pathoradiological correlation of pulmonary candidiasis in immunosuppressed patients. Cancer 40:1026-1036 1977[Medline]

3. Masur H, Rosen PP, Armstrong D: Pulmonary disease caused by Candida species. Am J Med 63:914-925 1977[Medline]

4. Haron E, Vartivarian S, Anaissie E, et al: Primary Candida pneumonia: Experience at a large cancer center and review of the literature. Medicine (Baltimore) 72:137-142 1993[Medline]

5. Goodrich JM, Reed EC, Mori M, et al: Clinical features and analysis of risk factors for invasive candidal infection after marrow transplantation. J Infect Dis 164:731-740 1991[Medline]

Response

Johannes Gutenberg-University, Mainz, Germany

In Reply: Dr Martino addresses the difficulty of evaluating Candida species from BAL fluids. We clearly agree with his opinion. One intention of our study was to determine a correlation of underlying organisms with HRCT patterns at a very early stage of neutropenic fever. Therefore, the HRCT patterns of patients who reached an end point were listed with frequently detected micro-organisms, and the data were analyzed. Assignment of a particular radiologic pattern, pattern distribution, or combination of patterns to any micro-organism was, as expected, too heterogeneous and therefore impossible. This holds especially true for the 20 cases of positive cultures for Candida species. Evidence of Candida species in these cases was not considered a verification of Candida pneumonia. Table 6 simply describes microbiologic and radiographic data. Defining new diagnostic criteria for Candida pneumonia was not intended, although the title of Table 6 might be misleading. Most (14 of 20) of these patients, however, can be classified as having probable invasive fungal infection according to the European Organization for Research and Treatment of Cancer/MSG criteria, and two further patients had positive blood cultures of Candida species. However, these patients did reach other end points of this study (defined as pneumonia on chest x-ray or other relevant micro-organisms). Thus, there is no change in the results or the conclusions of this study, which demonstrated inflammatory pulmonary disease by HRCT in more than 50% of the febrile neutropenic patients despite normal chest roentgenograms.

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