Dumont, Philippe

Garzoni, Christian

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CORRESPONDENCE • CID 2008:46 (1 March) • 7831 M A R C HCorrespondenceRate of Complicationsin ImmunocompromisedPatients and UnexpectedlyHigh Proportion ofZygomycetes in ComputedTomography–GuidedPercutaneous Lung BiopsySpecimensTo the Editor—We read with great in-terest the article by Lass-Flo¨rl et al. [1]about the utility of examination of CT-guided lung biopsy specimens for diag-nosis of invasive fungal infection in im-munocompromised patients. For greaterappreciation and to generalize the article’sfindings, some issues need additionalclarification.First, CT-guided transthoracic needlebiopsy of the lung has become a commonprocedure to elucidate the nature of pul-monary nodules [2]. The diagnostic per-formance of this procedure for tumors de-pends on the size, location, and radiologicand histologic characteristics of the lesion,and the procedure is reported to have highsensitivity and specificity for malignancy[3]. At present, studies of the diagnosticaccuracy of this approach are scarce in thecontext of invasive pulmonary mycosis.The technique is reported to have aconsiderable rate of complications in sev-eral reports, and we have some concernregarding potentially severe complicationsin the studied population. Although pneu-mothorax is reported to occur in 8%–60%of patients, it seldom requires drainage(1%–13% of patients) among personswho present with pulmonary nodules [4–6]. Use of a thoracic tube to treat pneu-mothorax in immunocompromised pa-tients may constitute an important riskfactor for infection. Major hemorrhage,which is considered to be a very rare ad-verse event following CT-guided needlebiopsy, may also constitute a relevant haz-ard in invasive pulmonary aspergillosis.Patients with hematologic malignanciesand invasive pulmonary mycosis have anincreased risk of developing bleeding com-plications due to both thrombocytopeniaand hypervascularization of the lesion.Therefore, it would be of great interest tohave additional detailed data about therate of complications in the described im-munocompromised population.Second, thrombocytopenia is commonin patients with hematologic malignancies.The described technique is contraindi-cated for patients with platelet counts!50,000 platelets/mL. We are concernedthat there was no information about plate-let counts and transfusion. In our opinion,Lass-Flo¨rl et al. [1] should have providedthe percentage of patients with hemato-logic malignancies for whom this diag-nostic approach would have been contra-indicated and who required platelettransfusion.Third, the authors documented an un-expectedly high proportion of patientswith Zygomycetes infection (13 [21.3%]of 61 patients). This finding is of greatconcern and could have major conse-quences in clinical practice, because drugsthat are commonly used for these patients(e.g., voriconazole and echinocandins) arenot effective against these fungi. There-fore, we asked ourselves whether the highrates of Zygomycetes infection observedby the authors could be associated withlocal epidemiologic features, prophylacticregimens, and/or greater diagnostic ac-curacy of their approach. The generallyobserved increase in the rate of zygomy-cosis seems to be associated with the typeof prophylaxis administered [7, 8], as re-flected by the relationship between the useof voriconazole prophylaxis and the in-creased frequency of zygomycosis docu-mented in several recent reports [9, 10].Additional information on local, specificfungal epidemiology, the prophylactic reg-imens used for solid-organ transplant re-cipients, and hematologic malignancies inthe studied population should have beenprovided to clarify the high rate of Zy-gomycetes infection.AcknowledgmentsPotential conflicts of interest. C.G. and P.D.:no conflicts.Christian Garzoni1 and Philippe Dumont2Divisions of 1Infectious Disease and 2PulmonaryMedicine, University Hospital, Berne, SwitzerlandReferences1. Lass-Flo¨rl C, Resch G, Nachbaur D, et al. Thevalue of computed tomography–guided per-cutaneous lung biopsy for diagnosis of inva-sive fungal infection in immunocompromisedpatients. Clin Infect Dis 2007; 45:101-4.2. Klein JS, Zarka MA. Transthoracic needle bi-opsy: an overview. J Thorac Imaging 1997; 12:232–49.3. Wahidi MM, Govert JA, Goudar RK, GouldMK, McCrory DC. Evidence for the treatmentof patients with pulmonary nodules: when isit lung cancer? ACCP evidence-based clinicalpractice guidelines (2nd edition). Chest2007; 132(Suppl 3):94-107.4. Geraghty PR, Kee ST, McFarlane G, RazaviMK, Sze DY, Dake MD. CT-guided transtho-racic needle aspiration biopsy of pulmonarynodules: needle size and pneumothorax rate.Radiology 2003; 229:475–81.5. Muehlstaedt M, Bruening R, Diebold J,Mueller A, Helmberger T, Reiser M. CT/fluo-roscopy-guided transthoracic needle biopsy:sensitivity and complication rate in 98 pro-cedures. J Comput Assist Tomogr 2002; 26:191–6.6. Tomiyama N, Yasuhara Y, Nakajima Y, et al.CT-guided needle biopsy of lung lesions: asurvey of severe complication based on 9783biopsies in Japan. Eur J Radiol 2006; 59:60–4.7. Kauffman CA. Zygomycosis: reemergence ofan old pathogen. Clin Infect Dis 2004; 39:588–90.8. Malani AN, Kauffman CA. Changing epide-miology of rare mould infections: implicationsfor therapy. Drugs 2007; 67:1803–12.9. Siwek GT, Dodgson KJ, Magalhaes-SilvermanM, et al. Invasive zygomycosis in hematopoi-etic stem cell transplant recipients receiving784 • CID 2008:46 (1 March) • CORRESPONDENCEvoriconazole prophylaxis. Clin Infect Dis2004; 39:584–7.10. Imhof A, Balajee SA, Fredricks DN, EnglundJA, Marr KA. Breakthrough fungal infectionsin stem cell transplant recipients receiving vor-iconazole. Clin Infect Dis 2004; 39:743–6.Reprints or correspondence: Dr. Christian Garzoni, Div. of In-fectious Disease, Inselspital, Berne University Hospital, 3010Berne, Switzerland (christian.garzoni@insel.ch).Clinical Infectious Diseases 2008; 46:783–4 2008 by the Infectious Diseases Society of America. Allrights reserved. 1058-4838/2008/4605-0023$15.00DOI: 10.1086/527566Reply to Garzoniand DumontTo the Editor—We thank Garzoni andDumont [1] for their correspondence andappreciate their interest in our study re-garding the value of CT-guided percuta-neous lung biopsies [2] for diagnosis offungal infection.Invasive fungal infection is a majorcause of morbidity and mortality in im-munosuppressed patients. Case-fatalityrates range from 30% to 80% among neu-tropenic patients, and deaths result, atleast in part, from difficulties in obtaininga reliable diagnosis [3]. However, only anaccurate diagnosis allows for a specifictherapy directed against the cause of theinfiltrates, allows elimination of unnec-essary and potentially toxic antimicrobialagents, and facilitates a more rational ap-proach to the treatment of these criticallyill patients. Tissue samples represent themost satisfactory specimens for use in di-agnosis of invasive fungal infection [4].Thus far, there has been no doubt thatperformance of CT-guided percutaneouslung biopsy in immunocompromised pa-tients is a risk for potential complications.Contraindications, such as pulmonaryhemorrhage with hemoptysis and infec-tion, may account for these risks [5]. Inour cohort of 61 patients, there were noemergencies that required treatment of he-moptysis, although 1 patient experiencedpneumothorax requiring chest tube place-ment. The timing of lung biopsy dependedon the patient’s condition. The intervalfrom radiologic diagnosis to biopsy inter-vention was 9 days (range, 4–22 days).Biopsy specimens were not obtainedduring severe neutropenia (absolute neu-trophil count, !500 cells/mL) or throm-bocytopenia (platelet count, !50,000platelets/mL). Five patients received plate-let transfusions.Zygomycetes infections are non-Asper-gillus mold infections and are importantcauses of morbidity and mortality amongimmunocompromised patients [6]. Analarming increase in the number of casereports of zygomycosis have been notedamong patients with cancer over the pastdecade [7]. However, center-to-center dif-ferences occur, and there is a lack ofknowledge regarding the reasons for thisepidemiologic shift. One proposed pre-disposing factor is the widespread use ofvoriconazole as prophylaxis for patientswho have hematologic malignancies orwho have undergone hematopoietic stemcell transplantation. Conversely, some re-searchers have suggested that the associ-ation is not causative but rather a reflec-tion of changes in the host’s immuneconstitution or time at risk while receivingimmunosuppressive drugs [8]. In ourhealth care center, prophylaxis and treat-ment strategies accord with internationalguidelines and recommendations [9, 10].Patients who have hematologic malignan-cies and/or who have undergone alloge-neic or autologous stem cell transplanta-tion received standard prophylaxis withfluconazole (400 mg/day). For empirical,preemptive treatment of invasive fungalinfection, therapy was switched to eithera lipid formulation of amphotericin B orvoriconazole. Overall, the rate of infectiondue to Zygomycetes increased in our hos-pital, as well as in other health care centers,indicating the necessity for a powerfulmeans of diagnosis to reduce the highmortality for this condition.AcknowledgmentsPotential conflicts of interest. All authors: noconflicts.Cornelia Lass-Flo¨rl,1 Martin C. Freund,2and David Nachbaur31Department of Hygiene and Social Medicine,University of Innsbruck, and 2Department ofRadiology and 3Clinical Division of Hematologyand Oncology, Innsbruck Medical University,Innsbruck, AustriaReferences1. Lass-Flo¨rl C, Resch G, Nachbaur D, et al. Thevalue of computed tomography–guided per-cutaneous lung biopsy for diagnosis of inva-sive fungal infection in immunocompromisedpatients. Clin Infect Dis 2007; 45:101–4.2. Garzoni C, Dumont P. Complications rate andunexpected high proportion of zygomycetesin computed tomographic–guided percuta-neous lung biopsy in immunocompromisedpatients. Clin Infect Dis 2008; 46:783–4 (inthis issue).3. Denning D. Invasive aspergillosis. Clin InfectDis 1998; 26:781–805.4. Kim K, Lee M, Kim J, et al. Importance ofopen lung biopsy in the diagnosis of invasivepulmonary aspergillosis in patients with he-matologic malignancies. Am J Hematol2002; 71:75–9.5. Nosari A, Anghilieri M, Garrafiello G, et al.Utility of percutaneous lung biopsy for diag-nosing filamentous fungal infections inhematologic malignancies. Haematologica2003; 88:1405–9.6. Almyroudis N, Sutton D, Linden P, et al. Zyg-omycosis in solid organ transplant recipientsin a tertiary transplant center and review ofthe literature. Am J Transplant 2006; 6:2365–75.7. Chamilos G, Marom E, Lewis R, et al. Pre-dictors of pulmonary zygomycosis versus in-vasive pulmonary aspergillosis in patients withcancer. Clin Infect Dis 2005; 41:60–6.8. Trifilio SM, Bennett C, Yarnold PR, et al.Breakthrough zygomycosis after voriconazoleadministration among patients with hema-tologic malignancies who receive hematopoi-etic stem-cell transplants or intensive che-motherapy. Bone Marrow Transplantation2007; 39:425–9.9. Bo¨hme A, Ruhnke M, Buchheidt D, et al.Treatment of fungal infections in hematologyand oncology—guidelines of the InfectiousDiseases Working Party (AGIHO) of theGerman Society of Hematology and Oncology(DGHO). Ann Hematol 2003; 82(Suppl 2):133–40.10. Stevens D, Kan VL, Judson, MA, et al; Infec-tious Diseases Society of America. Practiceguidelines for diseases caused by Aspergillus.Clin Infect Dis 2000; 30:696–709.

Rate of Complications in Immunocompromised Patients and Unexpectedly High Proportion of Zygomycetes in Computed Tomography-Guided Percutaneous Lung Biopsy Specimens

Rate of Complications in Immunocompromised Patients and Unexpectedly High Proportion of Zygomycetes in Computed Tomography-Guided Percutaneous Lung Biopsy Specimens

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