Legionella Jordanis in Hematopoietic SCT Patients Radiographically Mimicking Invasive Mold Infection
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Bone Marrow Transplantation (2011) 46, 1099–1103 & 2011 Macmillan Publishers Limited All rights reserved 0268-3369/11 www.nature.com/bmt ORIGINAL ARTICLE Legionella jordanis in hematopoietic SCT patients radiographically mimicking invasive mold infection This article has been corrected since Advance Online Publication and a corrigendum is also printed in this issue R Meyer1, U Rappo2, M Glickman2, SK Seo2, K Sepkowitz2, J Eagan3 and TN Small1 1Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 2Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA and 3Infection Control, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Opportunistic pulmonary infections are a major cause of tions, occurring early or late in the post-transplant course, post-transplant morbidity and mortality. Among these range from pulmonary edema, hemorrhage, engraftment infections, Aspergillus is a common cause of fatal syndrome, bronchiolitis obliterans, GVHD to, most pneumonia. Owing to the precarious clinical condition of commonly, infection. Since the advent of chemoprophy- many patients who acquire invasive mold infections, laxis against Pneumocystis carinii and preemptive or clinicians often treat them on the basis of radiographic prophylactic strategies against CMV, currently the most findings, such as the halo sign. However, in patients who common infectious organisms include invasive mold, do not respond to treatment or who have uncommon adenovirus and bacterial pathogens.2–4 Pulmonary infec- presentations, bronchoscopy or lung biopsy looking for tions are often treated empirically, presumptively diag- other pathogens should be considered. This study describes nosed based on clinical signs and symptoms, radiographic two cases in which the radiographic halo signs character- findings and noninvasive microbiological results, including istic of Aspergillus were in fact due to Legionella jordanis, assessment of DNA or RNA viremia, b-D-glucan and a pathogen that has been culture proven only in Aspergillus galactomannan Ag. Although bronchoscopy two patients previously (both of whom had underlying and biopsy would ideally be undertaken, thrombocytopenia lung pathology) and diagnosed by serologic evidence in and unstable hemodynamic and pulmonary status often several other patients. In immunocompromised patients, preclude their safe undertaking in this patient population. Legionella can present as a cavitary lesion. Thus, Nevertheless, aggressive pursuit of infected tissue for presumptive treatment for this organism should be pathology and culture has the potential to clarify the considered in post-transplant patients who do not have a infecting organism and reduce empiric antimicrobial classic presentation for invasive fungal infection and/or therapy. We describe two cases in which classic presenta- who fail to respond to conventional treatment. These cases tions suggested invasive mold. Instead, biopsy results illustrate the importance of obtaining tissue cultures to indicated Legionella jordanis. differentiate among the wide variety of pathogens present in this patient population. Bone Marrow Transplantation (2011) 46, 1099–1103; doi:10.1038/bmt.2011.94 Patients and methods Keywords: opportunistic infections; Legionella; invasive fungal infection The first patient was a 30-year-old West-Indian man with Ph chromosome-positive CML who underwent a 5/6 HLA- mismatched unrelated BMT, T cell depleted with the T10B9 MoAb and complement.5 His cytoreduction con- sisted of TBI, cytarabine and CY. He received cyclosporine Introduction and corticosteroids for GVHD prophylaxis as described previously.5 The patient developed biopsy-proven skin Pulmonary complications occur in nearly half of all GVHD on day þ 31, which was treated successfully with patients undergoing hematopoietic SCT.1 These complica- topical and systemic steroids and the anti-IL-2 receptor, daclizumab. On transplant day 69, the patient was hospitalized owing to fever, cough and 12-pound weight loss. Chest radiograph Correspondence: Dr R Meyer, Department of Pediatrics, Memorial showed a focal nodular density in the superior segment of Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. the right lower lobe (Figure 1). A chest computed E-mail: [email protected] tomography (CT) scan demonstrated a single 3-cm round Received 19 January 2011; accepted 17 February 2011 mass (Figure 2). The patient was treated with ticarcillin/ Legionella jordanis in HSCT patients R Meyer et al 1100 Figure 3 Follow-up chest CT showing lung nodule with central cavita- tion (performed on hospital day 10). Figure 1 Chest radiograph with right lower lobe focal nodular density (performed on hospital day 1). Figure 2 Chest CT that confirmed a 3 Â 3cm2 right lower lobe mass (performed on hospital day 2). Figure 4 Chest CT on readmission, showing increased numbers of right clavulanate and amikacin, continued on itraconazole, and lower lobe nodules, mostly cavitary. amphotericin B deoxycholate was added owing to concern regarding subtherapeutic serum itraconazole levels. A random measurement of the itraconazole level on hospital amphotericin B. Two weeks following admission, he day 9 was o0.5 mcg/mL, prompting a 33% increase in underwent a right-sided video-assisted thoracoscopic itraconazole dose. Bronchoscopy performed on hospital surgery (VATS) with right lower lobe wedge resection. day 6 (day þ 75) was non-diagnostic. The patient had Pathology showed interstitial pneumonitis. The biopsy was resolution of fever and cough, and a chest CT scan negative for granulomas or viral inclusions, but showed performed 1 week after initiation of broad-spectrum rare bacillary forms on modified Steiner stain. Immunoper- therapy showed the presence of a smaller pulmonary oxidase stains for CMV, EBV, adenovirus and toxoplas- nodule (1.7 cm) with central cavitation (Figure 3). The mosis were negative. Special stains for acid-fast bacteria patient was discharged on hospital day 21 to complete an and fungi were negative. Culture grew L. jordanis. Urine additional week of double antifungal coverage. Legionella Ag was negative. In light of these findings, At 48 h after discharge, the patient was readmitted with antimicrobial therapy was modified to include azithromy- fever, lethargy and cough, and crackles in the right mid- cin. Further history revealed that the patient took frequent axilla and lung base. WBC count on admission was long showers at home and in the hospital. Unfortunately, 3.9 cells/mm3, with absolute neutrophil and lymphocyte the patient subsequently developed CMV viremia and counts of 3.5 and 0.1 cells/mm3, respectively. Lymphoid multiple small central nervous system lesions suggestive of phenotyping showed a circulating CD4 cell count of 4/mL. cerebral toxoplasmosis and/or aspergillus, as well as new His chest CT scan showed an increase in the number and bilateral alveolar infiltrates and pleural effusions. Despite size of right lower lobe pulmonary nodules, many of which broad-spectrum antimicrobial therapy, diuresis and oxygen were cavitary (Figure 4). His serum cryptococcal Ag was support, his respiratory status deteriorated. He died on day negative. The patient was continued on itraconazole; his 149 post hematopoietic stem cell transplant (HSCT). His amphotericin B deoxycholate was changed to liposomal family declined autopsy. Bone Marrow Transplantation Legionella jordanis in HSCT patients R Meyer et al 1101 Figure 5 Right middle lobe opacity noted on portable chest X-ray. Figure 6 Chest CT demonstrating cavitary lesion. The second patient is a 17-year-old boy with Fanconi anemia who received an 8/10 HLA-matched unrelated T-cell-depleted transplant for myelodysplastic syndrome with clonal evolution. His cytoreduction consisted of single low-dose TBI, fludarabine and low-dose CY as described previously.6 His graft rejection prophylaxis consisted of pre-transplant rabbit anti-thymocyte globulin and short- course tacrolimus with rapid taper. His cytoreduction was truncated secondary to respiratory and hemodynamic decompensation of unknown etiology. His post-transplant course was complicated by vancomycin-resistant Entero- coccus bacteremia on day þ 8 post HSCT and EBV (peak copy number was 535 000 copies/mL on day þ 62). His EBV viremia was treated successfully with five doses of rituximab. On day 104 post transplant, the patient presented with Figure 7 Gram-negative bacillus (later identified as L. jordanis) isolated from needle aspiration of cavitary lung lesion ( Â 1000, courtesy of Fitzroy acute onset of right-sided pleuritic chest pain following a Edwards). minor car accident. On physical examination, he was afebrile, tachycardic. His lungs were clear, he was not tachypneic and his oxygen saturation was normal on room infiltration and epithelioid histiocytes consistent with air. His chest X-ray demonstrated a right middle-lobe granulomatous inflammation. He was treated with levo- opacification (Figure 5). CT scan showed a subpleural floxacin for 3 weeks, following which CT scan showed parenchymal opacification with a suggestion of peripheral resolution of lesions. The patient is now 20 months ground glass halo, felt to be consistent with a fungal post-transplant, clinically well, with an absolute CD4, infection (Figure 6). He had a normal WBC count, Hb, CD8 and CD19 cell count of 161, 642 and 222 cells/mL, mild thrombocytopenia, normal electrolytes, elevated liver respectively. His PHA response