key: cord-0994352-ce5ic04g authors: Sakata, Kenneth K.; Klassen, Christine L.; Bollin, Kathryn B.; Grys, Thomas E.; Slack, James L.; Wesselius, Lewis J.; Vikram, Holenarasipur R. title: Microbiologic yield of bronchoalveolar lavage specimens from stem cell transplant recipients date: 2017-04-12 journal: Transpl Infect Dis DOI: 10.1111/tid.12684 sha: 26e39a05d268e4412adaeda4d58ad572d2995774 doc_id: 994352 cord_uid: ce5ic04g PURPOSE: Stem cell transplant (SCT) recipients commonly undergo bronchoalveolar lavage (BAL) collection as an infectious pulmonary work‐up. Previous studies report the utility and overall diagnostic yield of fiberoptic bronchoscopy with BAL in this vulnerable population, though none focused purely on microbiologic yield or made comparisons with less invasive means of pathogen detection. We sought to determine and elaborate on the microbiologic yield of BAL in SCT recipients, assess a correlation between BAL studies and less invasive means of pathogen detection, and assess the utility of repeating a BAL within 30 days. METHODS: Between January 1, 2009, and July 31, 2013, we reviewed medical records of 125 SCT recipients who underwent 179 BALs. In addition to demographic information and details pertaining to their SCT, a comprehensive review of their microbiologic data was performed and recorded. RESULTS: Our study showed an overall BAL microbiologic yield of 40%, despite 92% of patients receiving broad‐spectrum antimicrobial therapy at the time of the BAL procedure. CONCLUSIONS: Although an initial BAL sample in this population provides crucial microbiologic information, repeating the procedure within 30 days may have minimal additional microbiologic yield. BAL continues to be an essential diagnostic tool in SCT recipients undergoing an infectious pulmonary work‐up. often requires both computed tomography (CT) and fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL). FOB with BAL has generally been considered a safe and valuable procedure for evaluation of pulmonary complications in SCT recipients undergoing an infectious pulmonary work-up. [3] [4] [5] [6] The BAL specimen is evaluated with an array of diagnostic microbiologic studies targeting various pathogens, including bacteria, mycobacteria, fungi, and viruses. Prior published studies have reported a diagnostic yield of BAL ranging from 31% to 80%. 2, 3, [5] [6] [7] [8] [9] [10] [11] [12] [13] The data often combine the diagnostic yield of both infectious and noninfectious pulmonary complications in SCT recipients. Few reports focus exclusively on the microbiologic yield of BAL in SCT recipients. We therefore sought to determine and elaborate the overall microbiologic yield of BAL in recipients of autologous (auto-SCT) and allogeneic (allo-SCT) SCTs, who underwent an infectious pulmonary work-up at our institution. The study cohort consisted of 125 SCT recipients who underwent 179 BAL procedures between January 1, 2009 and July 31, 2013, at our institution as part of their infectious work-up for fever, respiratory symptoms, or new pulmonary radiographic abnormalities. For patients who had multiple bronchoscopy procedures, each encounter was considered as an independent procedure. Patients who had an auto-SCT before receiving an allo-SCT were counted toward the allogeneic dataset. The ICH BAL order set at our institution during the study period con- The following data were collected for each BAL (42%) identified a true pathogen respectively. The microorganisms isolated from BAL samples from both auto-and allo-SCT recipients are listed in Table 2 . Of the true pathogens isolated, 31% were bacteria, 24% fungi, 24% viruses, and 21% were mixed organisms. Of the BALs in which a true pathogen was identified, 92% of the patients had received broad-spectrum antimicrobial therapy in the 48 hours before BAL collection. Empirical antimicrobial therapy prior to BAL was administered to 88% and 94% in the auto-SCT and allo-SCT subgroups respectively. The following pathogens were evaluated in more detail: Pneumocystis jirovecii 3 5 Penicillium species 0 3 Saccharomyces species 0 3 Rhizopus species 0 3 Coccidioides species 0 3 Paecilomyces species 0 1 Trichoderma species 0 1 BAL, bronchoalveolar lavage; Auto-SCT, autologous stem cell transplant; Allo-SCT, allogeneic stem cell transplant; ESBL, extended spectrum β-lactamase-producing. Pneumocystis jirovecii, Coccidioides species, and viruses. Table 3 summarizes the clinical information of patients with these pathogens. MRSA was isolated in 5 BAL cultures. Fourteen BAL cultures revealed Pseudomonas-2 were collected from auto-and 12 from allo-SCT recipients. One of these had a concur- Legionella was isolated in 5 BAL cultures-2 were retrieved from autoand 3 from allo-SCT. All 5 had a concurrent positive BAL Legionella PCR. Two cases were diagnosed within 5 days of each other (one on the day of admission and requiring intensive care unit admission; the other, 5 days later Twenty BALs were positive for Aspergillus species-5 were from autoand 15 from allo-SCT patients. Three different methods were used to assess for the presence of Aspergillus: BAL culture, BAL AspAg, and serum AspAg. Eight positive results were detected for BAL P. jirovecii PCR-3 were detected from auto-and 5 from allo-SCT patients. All 8 cases had a BAL P. jirovecii fluorescent smear tested and 1 tested positive. High-dose corticosteroid therapy was given in 2 cases and 3 cases received P. jirovecii prophylaxis (2 pentamidine and 1 trimethoprimsulfamethoxazole). The most common CT finding among the 8 cases was diffuse GGO (88%). Coccidioides species can be detected in the BAL with fungal smear, culture, or PCR. There were 3 positive cocci results on BAL PCR, of which 1 had a concurrent positive BAL culture (and negative serum cocci serology). All 3 positive BAL cocci PCRs were from allo-SCT patients. Serum cocci serologies were tested in 88 cases; 4 had positive cocci serologic results, of which 1 had a concordant BAL PCR. The most common radiographic finding on chest CT was consolidations with GGO. The most common viruses detected were EBV (n=16), followed by parainfluenza virus (n=14; 2 were isolated from auto-and 12 from allo- Fifteen BAL specimens had 2 or more concurrent pathogens, and the most common combination was bacterium and fungus (n=7), followed by fungus and virus (n=4) and by bacteria and virus (n=3). The other BAL specimen isolated all 3 of these pathogens. In this vulnerable population, FOB with BAL is considered to be a welltolerated, safe, and accurate procedure. 3 Complication rates of FOB with BAL in SCT recipients can be as low as 0%. 5 If transbronchoscopic lung biopsies are performed in addition to BAL, complication rates can be as high as 7%-15%. 4, 6 The safety profile and low complication rate of BAL 3 make it the most commonly used diagnostic tool in SCT recipients undergoing an infectious pulmonary work-up. 14 Administration of prophylactic or preemptive antimicrobial therapy is common in SCT patients because empirical antimicrobial therapy is associated with improved clinical outcomes. 16 However, early and aggressive use of such empirical regimens is conceptually thought to decrease the microbiologic yield of a BAL sample. In our cohort of patients who had a true pathogen identified on BAL, 92% had treatment with broad-spectrum antimicrobial therapy initiated at least 48 hours before BAL collection. In addition, 62% of our cohort with 39 BALs, who had detection of MRSA, Pseudomonas, or Aspergillus, or a combination of these, was taking appropriate therapy targeting these specific pathogens. Therefore, receipt of concurrent antimicrobial therapy should not dissuade the operator from performing a BAL in this patient population. MRSA pneumonia is associated with poor outcomes and frequently necessitates empirical antibiotic therapy. A recent study reported that a negative MRSA on PCR from a NS specimen had a 99% negative predictive value for MRSA pneumonia. 17 We report similar findings wherein 80 MRSA NSs were performed and 79 were negative. All 79 BAL and sputum cultures that were negative in these cases were negative for MRSA. In this series, 174 of 179 cases (97%) had a chest CT within 48 hours of FOB. Chest CT scans may be more sensitive than chest radiographs, and CT is now the standard diagnostic tool in the initial assessment of invasive pulmonary aspergillosis and other opportunistic pulmonary infections in SCT recipients. 22, 23 This was a retrospective study and thus has its inherent limitations. We did not assess the impact of BAL results on antimicrobial therapy (ie, alteration or initiation), morbidity, or death, because our study was designed only to analyze the microbiologic yield of BAL. Specific complication rates of FOB were not collected. This also was a single-institution study and the results may not be generalizable to SCT patients in other institutions or regions. To our knowledge, this is the largest retrospective study to date that looks at the microbiologic yield of FOB with BAL in SCT recipients. We were able to demonstrate that sputum cultures are unreliable in detecting pulmonary pathogens in this population. In addition, obtaining a BAL sample despite the patient receiving antimicrobial therapy for at least 48 hours before sample collection continues to be a valuable diagnostic test to consider in this immunosuppressed cohort. BAL is an essential diagnostic tool in SCT recipients undergoing an infectious pulmonary work-up. Our study showed an overall BAL microbiologic yield of 40% despite 92% of this group having received empirical broad-spectrum antimicrobial therapy before BAL collection. Although an initial BAL sample can provide critical microbiologic information, repeating a BAL within 30 days may not have additional diagnostic yield. 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