Positive Bronchoalveolar Lavage Research Articles

Impact of Screening and Treatment of Ureaplasma species on Hyperammonemia Syndrome in Lung Transplant Recipients: A Single Center Experience.

Infection with Ureaplasma species (spp) has been linked to fatal hyperammonemia syndrome (HS) in lung transplant recipients. We sought to characterize the epidemiology of Ureaplasma spp in candidates and donors and describe outcomes of antimicrobial therapy in preventing and treating HS. Candidate testing for Ureaplasma spp was performed with urine culture and polymerase chain reaction (PCR) pretransplant. Positive candidates were treated with levofloxacin. Donor testing was performed with bronchoalveolar lavage (BAL) culture and PCR intraoperatively. From 7/2014 to 2/2017 patients were treated according to results; from 2/2017 to 10/2018 recipients received empiric levofloxacin and azithromycin at transplant until testing returned negative. HS was defined as new onset altered mental status after transplant with ammonia > 200 µmol/L. In total, 60 patients who underwent lung transplant were included. And 80% (n = 48) of patients had negative screening tests in donor and candidate pre-lung transplant, 8.3% (n = 5) of recipients had positive Ureaplasma spp testing in urine pre-transplant, and 13.3% (n = 8) had positive donor BAL testing at the time of lung transplant. Three patients developed HS a median of 7 days posttransplant; 2 died of HS. Recipients of organs with Ureaplasma spp who received empiric therapy did not develop HS. Donors with Ureaplasma spp were younger and more sexually active. Donor-derived Ureaplasma spp in lung transplant was associated with HS. Screening lung donors for Ureaplasma spp might allow for targeted therapy to reduce risk for development of HS, but future confirmatory studies are needed.

A Retrospective Cohort Study of Risk Factors for Surgical Site Infection Following Lung Transplant.

Surgical site infections (SSIs) are among the leading health care-associated infections as well as a major problem in the postoperative period of lung transplant recipients. Little is known about the risk factors in this specific population. The objective of this study was to identify the incidence, risk factors, and outcomes of SSI following lung transplant. Digital medical records of adult recipients subjected to lung transplant from July 2011 and June 2016 in a large Brazilian referral teaching public center were analyzed in this retrospective cohort follow-up. Among the 121 recipients analyzed, 19 (15.7%) had SSI; of these, 11 (57.8%) had superficial incisional infections, 1 (5.2%) had a deep incisional infection, and 7 (36.8%) had organ/space infection. Recipient-related risk factors for SSI were high body mass index (P = .041), prolonged surgery time (P = .043), and prolonged duration of chest drain placement (P = .009). At the multiple logistic regression was found that each hour elapsed in the surgical time increased the odds of SSI by around 2 times (odds ratio 2.34; 95% CI, 1.46-4.53; P = .002). Donor-related risk factors included smoking status (P = .05) and positive bronchoalveolar lavage (P < .001). Having an SSI was associated with an increased length of stay in intensive care units (P = .003), reoperation (P = .014), and a higher 1-year mortality rate (P = .02). The identified incidence rate was higher to that observed in the previous studies. The risk factors duration of chest tube placement and donor smoking status are different from those reported in the scientific literature.

Ibuprofen does not prevent postbronchoscopy fever in children undergoing broncho-alveolar lavage.

Fiber-optic bronchoscopy (FOB) of the lower airways is a routine examination performed for investigating varying respiratory complaints in children. A common side effect is a transient high fever on the day of the FOB. Such episodes are usually unrelated to an infectious process but may cause clinical uncertainty and parental anxiety. We have previously shown that a single dose of systemic dexamethasone significantly reduces the rate of fever postbronchoscopy (FPB). To prospectively analyze the effect of a prophylactic dose of ibuprofen upon the FPB. Children presenting for elective FOB and broncho-alveolar lavage (BAL) were randomized, in a double-blind fashion, to receive a single dose of ibuprofen syrup 10 mg/kg or placebo prior to the procedure. Parents were contacted the next day to record the presence or absence of fever. Sixty-one children were included in the final analysis. Thirty-one children were in the treatment group and 30 in the placebo group. FPB occurred in 40 children (65%). There was no difference in the rate of FPB between placebo (63%) and treatment (67%) groups (P = .717). Fifty (82%) children had a positive BAL culture. Among them, 38 had FPB (76%) compared with only 2 of 11 (18%) of those with negative culture (P = .00026, relative risk 4.18). About 80% of positive cultures grew Haemophilus influenza. There was no significant difference between the number of BALs with a positive culture between the treatment and placebo groups (87% vs 77%, P = .35). FPB occurs in around twothirds of children when BAL is performed. Fever occurred significantly more frequently when BAL culture is positive. A single standard dose of the nonsteroidal anti-inflammatory drug ibuprofen administered before a FOB does not prevent FPB.

CORRELATION OF ENVIRONMENTAL MICROBIAL DIVERSITY WITH AIRWAY DISEASE IN REFRACTORY ASTHMA

TYPE: Abstract Publication TOPIC: Allergy and Airway PURPOSE: The influence of subacute bacterial infection in refractory asthma remains elusive. Bacterial dysbiosis and potentially environmental microbe exposures contribute to disease in asthma. We hypothesize that biodiversity within home environments influences airway microbiome and control of disease in refractory asthma. METHODS: We examined the microbiome of bronchoalveolar lavage (BAL) samples and home dust specimens of 5 refractory asthmatics, at time points 12 months apart. A custom, aggressive genomic DNA extraction was used to obtain a more diverse composition of microbial DNA. Bacterial 16S rDNA (V4-V5) was amplified, packaged into libraries, and sequenced in a multiplex manner using 2X300bp Illumina chemistry. Sequences were processed and profiled using QIIME2. Clinical parameters collected include BAL cell count differential, cultures, Asthma Control Test (ACT) and FEV1. RESULTS: Two subjects had positive BAL cultures, one with rare Pseudomonas and another with Mycobacterium. Follow-up bronchoscopy showed culture resolution and reduced airway neutrophilia after directed treatment. Subjects with clinical improvement (3 of 5) trended toward a significant increase in BAL biodiversity by genus (p=0.065, two-tailed T-test), and reduced environmental microbial DNA at month 12. Subjects without clinical improvement of asthma (2 of 5) demonstrated predominant pathogenic bacterial DNA and negative BAL cultures, therefore untreated clinically. CONCLUSIONS: Preliminary analysis of environmental and airway microbiome suggests asthma control is dependent on treatment of clinical and sub-clinical microbes. Higher airway and lower environmental biodiversity may correlate with improved asthma control. CLINICAL IMPLICATIONS: Our research shows clinical cultures are sub-optimal in identifying bacterial species in the lower airways. DISCLOSURE: No significant relationships. KEYWORDS: airway microbiome, refractory asthma

Factors Associated With Prolonged Antibiotic Use in the Setting of Suspected Pneumonia and Negative Bronchoalveolar Lavage Cultures.

Background: Diagnostic criterion for pneumonia includes clinical data and bronchoalveolar lavage cultures (BALCx) to identify pathogens. Although ~60% of BALCx are negative, there may be reluctance to discontinue antibiotics, leading to prolonged antibiotic use (PAU). Objective: The purpose of this study is to compare outcomes of subjects with negative BALCx with PAU versus without prolonged antibiotic use (nPAU). Methods: A retrospective cohort study was conducted including subjects admitted to the intensive care unit (ICU), with suspected pneumonia, and negative BALCx. Data were compared based on length of exposure to antibiotics, PAU (antibiotics >4 days) versus nPAU (antibiotics <4 days). Results: A total of 128 subjects were included, 57 in the PAU group and 71 in the nPAU group. Baseline demographics were similar between groups. Severity of illness measured by multiple organ dysfunction scores at time of bronchoalveolar lavage (BAL) collection to final result showed a statistically significant decrease in the PAU group but not in the nPAU group. No differences were found in ICU days, ventilator-free days, or mortality; however, length of stay was longer for PAU (23 vs. 17, p = .04). In the PAU group, there were fewer BALCx results of "no growth" (23% vs. 45%, p = .04), more positive gram stains (83% vs. 60%, p = .01) and more positive non-BALCx (40% vs. 14%, p = .01). In a multivariate analysis, factors associated with PAU were positive BAL gram stains (adjusted odds ratio [aOR] 3.1, p = .037) and positive non-BALCx (aOR 4.7, p = .002). Conclusion: For subjects with suspected pneumonia and negative BALCx, positive non-BALCx and positive BALCx gram stain influenced the length of exposure of antibiotics.

COVID-2019 outbreak: negative swab but positive bronchoalveolar lavage?

COVID-2019 outbreak: negative swab but positive bronchoalveolar lavage?

Late Onset Invasive Pulmonary Aspergillosis in Lung Transplant Recipients in the Setting of a Targeted Prophylaxis/Preemptive Antifungal Therapy Strategy.

Invasive pulmonary aspergillosis (IPA) is a significant cause of morbidity and mortality in lung transplant recipients (LTRs). It is unclear how a targeted prophylaxis/ preemptive antifungal therapy strategy impacts the incidence of IPA beyond the first-year posttransplant. This is a retrospective cohort of LTRs from January 2010 to December 2014. We included all LTRs who survived beyond the first year and followed them until death or 4 years postoperatively. Incidence of probable/proven IPA and Aspergillus colonization were assessed as per International Society for Heart and Lung Transplantation (ISHLT) criteria. Patients with risk factors, positive Aspergillus cultures, or galactomannan (GM) received targeted prophylaxis/preemptive therapy within the first-year posttransplant. During the study period, 350 consecutive LTRs underwent 1078 bronchoscopies. Positive bronchoalveolar lavage for GM or Aspergillus cultures was reported for 15% (52/350) of LTRs between 2 and 4 years after transplantation. Among them, the median time to positive Aspergillus culture or GM positivity was 703 days (interquartile range, 529-754 d). The incidence rate of IPA and Aspergillus colonization was 30 of 1000 patient-y, and 63 of 1000 patient-y, respectively. The mortality rate was significantly higher in patients with IPA than without IPA (107/1000 patient-years versus 18/1000 patient-years; P < 0.0001). Rate of first-year colonization and IPA was 33% and 9%, respectively. Among the 201 patients who had a negative bronchoscopy during the first year posttransplant, only 6 (3%) developed IPA during the follow-up. A targeted prophylaxis/preemptive therapy strategy within the first-year posttransplant resulted in 4% incidence of IPA at 4-years after transplantation. However, IPA was associated with higher mortality.

Assessment of a Loop-Mediated Isothermal Amplification (LAMP) Assay for the Rapid Detection of Pathogenic Bacteria from Respiratory Samples in Patients with Hospital-Acquired Pneumonia.

Rapid identification of the causative agent of hospital-acquired pneumonia (HAP) will allow an earlier administration of a more appropriate antibiotic and could improve the outcome of these patients. The aim of this study was to develop a rapid protocol to identify the main microorganisms involved in HAP by loop-mediated isothermal amplification (LAMP) directly from respiratory samples. First of all, a rapid procedure (<30 min) to extract the DNA from bronchoalveolar lavage (BAL), endotracheal aspirate (EA) or bronchoaspirate (BAS) was set up. A specific LAMP for Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii was performed with the extracted solution at 65 °C for 30–40 min. Overall, 58 positive BAL and 83 EA/BAS samples were tested. The limits of detection varied according to the microorganism detected. Validation of the LAMP assay with BAL samples showed that the assay was 100% specific and 86.3% sensitive (positive predictive value of 100% and a negative predictive value of 50%) compared with culture. Meanwhile for BAS/EA samples, the assay rendered the following statistical parameters: 100% specificity, 94.6% sensitivity, 100% positive predictive value and 69.2% negative predictive value. The turnaround time including sample preparation and LAMP was circa 1 h. LAMP method may be used to detect the most frequent bacteria causing HAP. It is a simple, cheap, sensitive, specific and rapid assay.

Bronchoalveolar lavage to evaluate new pulmonary infiltrates in allogeneic hematopoietic stem cell transplant recipients: impact on antimicrobial optimization

SummaryBackgroundPulmonary complications cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplant (AHSCT). Bronchoscopy with targeted bronchoalveolar lavage (BAL) is often used in AHSCT patients with suspected lower respiratory tract infection (LRTI) to help guide management.AimTo evaluate how positive BAL results change antimicrobial management of AHSCT recipients with suspected LRTI.MethodsWe performed a retrospective review of BAL results from January 2014 to July 2016 for 54 AHSCT recipients. A positive BAL was determined by culture, multiplex polymerase chain reaction (PCR), Aspergillus galactomannan antigen (AGA), and cytology.FindingsBAL was positive for infectious etiologies in 63%, and antimicrobials were adjusted in 48/54 (89%) of patients. Antibacterial escalation was predicted by a positive BAL bacterial culture (OR 7.61, P=0.017). Antibiotic de-escalation was more likely with an elevated AGA (OR 3.86, P=0.035). Antiviral initiation was more likely with positive BAL multiplex PCR (OR 17.33, P=0.010). Antifungals were more likely to be escalated or changed with an elevated AGA (OR 4.33, P=0.020). The patients with a negative BAL were more likely to be started on steroids (OR 0.19, P= 0.043).ConclusionsBAL was helpful to determine the etiology of pulmonary complications and optimize antimicrobials. The addition of AGA and multiplex PCR to standard BAL significantly impacted de-escalating antibiotics and adjusting antifungals to provide adequate coverage. The association with an elevated AGA with antibacterial de-escalation highlights a new role for BAL in antimicrobial optimization.

A positive BAL galactomannan in non-haemato-oncology patients risks harmful overtreatment.

Introduction. Evidence for the clinical utility of bronchoalveolar lavage (BAL) galactomannan in the management of fungal disease outside of haemato-oncology patients is limited.Aim. To determine how the introduction of BAL galactomannan testing impacted on the diagnosis and management of invasive aspergillosis and other fungal diseases in non-haemato-oncology patients.Methodology. Retrospective review of all adult patients (age ≥16 years) without a diagnosis of haematological malignancy who had a positive BAL galactomannan from 1 November 2014 to 30 April 2018. Using electronic patient records we obtained demographic data, clinical details, laboratory investigations, relevant radiology and antimicrobial history for each case.Results. In total, 121 episodes with a galactomannan OD index of ≥0.500 were included in the study; 29 cases (24 %) were felt to reflect fungal disease. Antifungal therapy was commenced as a direct consequence of a positive BAL galactomannan result in 13 patients where the ultimate diagnosis was subsequently considered to be non-mycological: associated medication-related side-effects in this group included deranged liver function tests (n=3), rash (n=1) and fever (n=1), related to amphotericin B (n=1) and voriconazole (n=4).Conclusion. We show that vigilance is required when interpreting galactomannan results in non-haematology patients to avoid potentially harmful overtreatment.

Abstract 378: Diagnosing Pneumonia After Cardiac Arrest

Introduction: Post cardiac arrest syndrome, therapeutic hypothermia, and CPR confound the clinical diagnosis of pneumonia. Accurate pneumonia diagnosis is required to improve targeted antibiotic allocation and prevent sequelae of untargeted antibiotic therapy. Hypothesis: We can rigorously define pneumonia after cardiac arrest (CA) using accepted clinical parameters adapted from existing guidelines and innate immune system biomarkers Interleukin-17A (IL-17A), integrin α9β1, and CD11b specific to the response to pulmonary infection. Methods: A prospective cohort of consecutive OHCA patients surviving at least 72 hours from arrival was enrolled. IL-17A, integrin α9β1, and CD11b were measured daily at 4 timepoints from time 0 (arrival) through 72 hours. Chest radiography, pulmonary microbiology, temperature, and white blood cell count were recorded concurrently from the medical record. Pneumonia was defined narrowly (pna_narrow) by the presence of at least 2 of the following criteria in the initial 72 hours of presentation: fever ≥38°C; persistent infiltrate on chest radiography; positive sputum or bronchoalveolar lavage per the hospital microbiology laboratory. Broad criteria (pna_broad) also incorporated persistent leukocytosis ≥15,000 or leukopenia &lt;3,000. Results: Of the 56 subjects with all data, 23% (13 of 56) met pna_narrow criteria while 43% (24 of 56) met pna_broad criteria. Positive clinical pulmonary microbiology was present in 62% (8 of 13) subjects meeting pna_narrow and 46% (11 of 24) subjects meeting pna_broad criteria. Antibiotics were given to 65% (28 of 43) subjects without pna_narrow and 63% (20 of 32) without pna_broad. Overall, 70% (39 of 56) subjects received antibiotics regardless of pneumonia status. Integrin α9β1 at Time 28 hours and Time 72 hours was associated with pna_narrow (p = 0.010, p = 0.049). CD11b at Time 0 and 72 hours was associated with pna_narrow (p = 0.03, p = 0.049). IL-17 at Time 28 and Time 72 was associated with pna_narrow (p = 0.04, p = 0.01). Conclusions: Pneumonia was rigorously defined in 23 to 43% of our sample, yet 70% of subjects received antibiotics. More rigorous definitions for pneumonia after CA, combined with pulmonary infection biomarkers, could be used to improve diagnosis and antibiotic allocation.

1771. Donor-derived Ureaplasma Infection Increases Mortality in Lung Transplant Recipients

BackgroundInfection with Ureaplasma species has been linked to fatal hyperammonemia syndrome (HS) in lung transplant (LTx) recipients (R). In this retrospective cohort, we sought to characterize the epidemiology of Ureaplasma spp in both candidates and donors and describe outcomes of antimicrobial therapy in preventing and treating HS.MethodsWe performed a retrospective cohort study of patients who received LTx at Northwestern Memorial Hospital from July 2014 to October 2018. Candidate testing for Ureaplasma spp. was performed with urine culture and PCR testing before LTx but after listing. Positive candidates were treated with levofloxacin for 14 days prior to undergoing LTx. Donor testing was performed with bronchoalveolar lavage (BAL) culture and PCR testing at organ implantation. From July 2014 to February 2017 LTxR were treated according to result; from February 2017 to October 2018 LTxR received empiric levofloxacin and azithromycin at the time of LTx until testing returned negative. HS was defined as new-onset altered mental status (AMS) after LTx with ammonia > 100; if no ammonia was tested, LTxR was classified as not developing HS. Summary and comparative statistics were performed using IBM® SPSS Statistics version 25.0.Results66 patients who underwent LTx and had candidate screening, donor screening, or both were included. 81.8% (n = 54) of patients had negative screening tests in donor and candidate pre-LTx, 7.5% (n = 5) had positive Ureaplasma spp. testing pre-LTx, and 12.1% (n = 8) had positive donor BAL testing at the time of LTx. One had positive candidate and donor screening (see Table 1). 3 patients developed HS a median of 6 days post-transplant; 2 died with HS as attributed cause. None received empiric therapy. LTxR with confirmed donor-derived infection were more likely to have mortality at 1 year when compared with LTxR with negative testing and candidates with positive testing pre-LTx (P = 0.019). LTxR with donor-derived infection were more likely to have AMS, higher peak ammonia, and require renal replacement therapy, although none reached significance (Table 2).ConclusionDonor-derived Ureaplasma spp. in LTxR was associated with increased mortality at one-year. Pre-transplant screening and treatment had no effect on the outcome. There is high concern for donor transmission and we advocate testing in all LTxR. Disclosures All authors: No reported disclosures.

Diagnostic value of bronchoalveolar lavage in the subset of patients with negative sputum/smear and mycobacterial culture and a suspicion of pulmonary tuberculosis

BackgroundThe diagnostic value of bronchoalveolar lavage in patients with negative sputum/smear for tuberculous bacilli has been well studied. However, its value in the subset of patients with both negative sputum/smear and culture is seldom reported. MethodsA retrospective study of patients referred for diagnostic bronchoscopy for the suspicion of pulmonary tuberculosis during the period from April 1st, 2015 to March 30th, 2016, and who had negative sputum/smear and culture for tuberculous bacilli. ResultsOne hundred and ninety patients fulfilled the inclusion criteria. Bronchoalveolar lavage detected further 61/190 (32.1%) pulmonary tuberculosis cases. Bronchoalveolar lavage mycobacterial culture and polymerase chain reaction (positive in 60/190 (31.6%) and 58/190 (30.5%) of patients respectively) provided the highest diagnostic yield, whereas direct smear provided the lowest yield. Bronchoalveolar lavage had a sensitivity of 89.7%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 94.6%, and a test accuracy of 96.3% in suspected pulmonary tuberculosis cases with negative sputum/smear and culture. Positive bronchoalveolar lavage yield for tuberculosis was significantly associated with a positive QuantiFERON-TB Gold In-Tube test, positive purified protein derivative skin test, radiological evidence of upper zone abnormality and patient’s origin being from the Indian subcontinent. ConclusionBronchoalveolar lavage should be pursued as a useful diagnostic tool for suspected pulmonary tuberculosis cases when sputum/smear and culture are negative. Its value is higher in the subset of patients with positive QuantiFERON-TB Gold In-Tube test, positive purified protein derivative skin test, upper zone abnormality on radiograph or being from the Indian subcontinent.

Do Peri-Transplant Respiratory Viral Infections Increase Incidence of Idiopathic Pneumonia Syndrome or Bronchiolitis Obliterans in Pediatric Pateints?

BackgroundUpper respiratory viral infections are common in the pediatric population. Idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans (BO) are rare, but devastating and life-threatening complications post hematopoietic stem cell transplant (HSCT). It has been suggested in work by others that IPS and BO are consequences of early inflammation, and recent data support this hypothesis (Versluys et al, Translational and Clinical Immunology, 2018). Respiratory viral infections early in the peri-transplant period may result in inflammation leading to development of IPS and BO post HSCT.ObjectivesThe primary objective of this study was to determine whether pre-transplant respiratory viral infection or colonization increase incidence of IPS and BO. We hypothesized that patients who acquire respiratory viral infections in the peri-transplant period have increased incidence of IPS and BO.MethodsWe abstracted and analyzed clinically collected data and compared the frequency of post-transplant respiratory viral complications with the presence of upper respiratory viral infections within 30 days prior to transplant. A Broncho alveolar lavage (BAL) or a nasal swab were used to identify upper respiratory viral infections. Epstein Barr virus (EBV), cytomegalovirus (CMV) and other upper respiratory viral infections were tested in 181 patients, transplanted between 2008 and 2018. Outcomes studied included IPS, BO, transplant associated thrombotic microangiopathy (TMA), graft versus host disease (GVHD), and overall survival (OS). Patients who did not have a BAL or a nasal swab within 30 days prior to transplant were excluded.ResultsForty seven of 181 patients had a positive BAL or nasal swab prior to HSCT (group A). There were 53 documented respiratory viral infections in group A. Two tested positive for either coronavirus, herpes simplex virus (HSV) or para-influenza virus, 3 tested positive for adenovirus, human herpes 6, influenza, or respiratory syncytial virus (RSV), EBV and CMV were detected in 9 patients, 1 patient had human metapneumovirus and there were 16 rhino virus infections documented prior to HSCT. Some patients tested positive for more than 1 respiratory viral infection at the time of testing.Results of our study are summarized below in Figure 1.ConclusionContrary to our hypothesis, our data do not support an association between upper respiratory viral infections prior to transplant and post-transplant IPS or BO. Our data may differ from the findings of others due to a relatively small number of events in our population, or to differences in patient populations being studied, or to differences in transplant strategies.

2032. Predictors of 6-Week Mortality in Patients with Positive Bronchoalveolar Lavage (BAL) Galactomannan (GM)

BackgroundBAL-GM is a mycologic criterion for diagnosis of probable invasive aspergillosis (IA). However, in a contemporary cohort of consecutive patients with BAL-GM measured as part of their workup for potential IA, we previously showed that 42% of positive (≥0.5) BAL-GM values can be falsely positive; positive predictive value was increased by using higher cutoffs and in patient groups with high pre-test probability for IA. In this study from the same cohort, we analyze the prognostic value of BAL-GM and identify predictors of 6-week mortality, the main outcome in most studies of mold-active antifungal drugs.MethodsWe reviewed clinical and microbiologic data of patients who had ≥1 positive BAL-GM (≥0.5), at Brigham and Women’s Hospital (November 2009–March 2016). We applied EORTC/MSG invasive mold infection (IMI) definitions to classify cases as possible, probable or proven IMI, excluding BAL-GM result as mycologic criterion, and used Cox regression to identify factors associated with 6-week all-cause mortality.ResultsWe studied 134 patients (median age 58 years, 49% women, 55% with hematologic malignancy, 10% solid-organ and 34% hematopoetic stem-cell transplant recipients). APACHE II score, liver disease, acute kidney injury, and shock were independently associated with higher 6-week mortality. ICU stay, mechanical ventilation, corticosteroids, hypertension, EORTC/MSG category, serum-GM and antifungal treatment were associated with higher mortality in univariate, but not multivariate analyses. BAL-GM value was independently associated with 6-week mortality (adjusted HR 1.24(continuous variable), 95% CI 1.1–1.39, P < 0.001). The association of BAL GM strata with 6-week crude mortality was significant in patients with possible, probable or proven IMI, but not in those without IMI (Figure 1). ConclusionHigher BAL-GM values were an independent predictor of 6-week mortality, having prognostic value in patients with possible, probable or proven IMI, but not in patients who did not meet other criteria for IMI. We propose critical reassessment of BAL-GM cutoff values in different patient populations.Figure 1.Kaplan–Meier (KM) curves for different cutoffs of BAL GM.Disclosures All authors: No reported disclosures.

2038. Invasive Mucormycosis Management: Mucorales PCR Provides Important, Novel Diagnostic Information

BackgroundIn immunocompromised patients, high mortality and morbidity of invasive mucormycosis (IM) remain significant healthcare issues due in part to confusion of IM with invasive aspergillosis (IA) and failure to initiate appropriate therapy. A validated Mucorales (MUC) PCR detects the causative agents of IM with good sensitivity and specificity, as reported previously (M-227, ICAAC 2013). Published studies have not definitively determined the frequency of patients for whom pulmonary IA is suspected but IM is present. We aimed to (1) estimate the frequency of MUC PCR positivity in bronchoalveolar lavage (BAL) samples submitted for Aspergillus (ASP) PCR panel testing.MethodsWe identified 1,067 clinical BAL specimens originally submitted to a reference laboratory for ASP PCR panel testing. Eluates from DNA extraction were tested by MUC PCR, which detects known pathogens from seven Mucorales genera (Apophysomyces, Cunninghamella, Lichtheimia [previously Absidia], Mucor, Rhizomucor, Rhizopus and Saksenaea).ResultsThe proportions of MUC PCR and ASP PCR positive BAL specimens were 1.5% (16) and 6.9% (74), respectively. 87.5% (14/16) of the MUC positive (POS) were ASP negative (NEG). One patient had two MUC PCR POS BAL samples within the testing period. The MUC quantification averaged 20,000 copies per mL BAL (range 24–266,000), which is >1,000-fold above the assay the 20 copies/mL limit of detection (LOD). Two of the ASP POS’s were MUC POS (~400 and 20-fold above LOD). For patients with MUC POS BALs, physicians requested on average 6.3 pneumonia-related tests (e.g., ASP PCR, Galactomannan, Legionella PCR, etc.) within 2 weeks of the tested BAL. In total 94.0% (85/91) of these orders yielded NEG results. The MUC PCR was physician-ordered in only one (6.25%) of the MUC POS BALs.ConclusionIn BAL samples submitted for IA testing, 16 cases (1.5%) had POS MUC PCR. The observed 5:1 (ASP:MUC) ratio approximates published literature on invasive mould incidence. MUC POS concurrent with NEG results for other pathogens suggest potential missed opportunities for MUC early diagnosis and treatment in cases of suspected invasive mould.Disclosures K. Wilgers, Viracor Eurofins Clinical Diagnostics: Employee, Salary. J. Waddell, Viracor-Eurofins: Collaborator, No financial benefit. A. Tyler, Viracor Eurofins Clinical Diagnostics: Employee, Salary. M. Altrich, Viracor Eurofins Clinical Diagnostics: Employee, Salary. S. Kleiboeker, Viracor Eurofins Clinical Diagnostics: Employee, Salary. D. Yin, Viracor-Eurofins: Collaborator, No financial benefit. ; Marion Merrell Dow Fund: Grant Investigator, Research grant. ; Astellas: Investigator, Research grant. ; Merck: Investigator, Research grant. M. Wissel, Viracor Eurofins Clinical Diagnostics: Employee, Salary.

356. Bronchoalveolar Lavage Fluid Cytology by GMS Stain for the Diagnosis of Invasive Pulmonary Aspergillosis in Patients With Hematologic Malignancies: Analysis of 67 Episodes

BackgroundThe yield of direct fungal visualization by GMS (Gomori–methenamine–silver) stain in bronchoalveolar lavage (BAL) cytology has rarely been studied in the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancies (HM).MethodsWe analysed a series of patients with proven or probable culture-documented IPA (EORTC/MSG criteria) in HM patients (1999–2015). All patients had BAL cultures that were positive for Aspergillus spp. and had concurrently obtained BAL cytology GMS available for analysis.ResultsWe identified 67 such patients. BAL cytology based on GMS showed hyalohyphomycetes consistent with Aspergillus in 28/67 (41.8%) patients, whereas only in 2/67 (3.6%) direct smear Calcofluor White stain was positive. Based on BAL GMS cytology, co-infections were identified in six patients: two Pneumocystis and five viral infections with cytopathic changes (one had both). The yield of cytology was not different in patients with IPA caused by non-fumigatus Aspergillus, although patients with IPA and >1 Aspergillus in BAL culture had more often positive cytology GMS (100% vs. 0%, p 0.027). Cytology was also more often positive when obtained from a lesion-targeted BAL as compared with non-targeted bronchial washings (60.7% vs. 7.1%, p 0.038). Patients with IPA and cavitary lesions (32.1% vs. 5.1%, P = 0.006), history of SCT (64.3% vs. 33%, P = 0.015) or prior exposure to itraconazole (75% vs. 41%, P = 0.007) had positive cytology GMS results more often than did patients without these characteristics. In the multivariate analysis, only cavitary lesions were significantly associated with positive BAL GMS cytology.ConclusionGMS stain in cytology of BAL in patients with HM and culture-documented IPA had a sensitivity of 41.8% and was more often positive in patients with cavitary lesions. Although there were no differences in the proportion of GMS-positive cytology rates among differing Aspergillus spp. causing IPA, mixed Aspergillus spp. IPA was associated with an increase in positive cytology. BAL cytology was diagnostic for co-infections in more than 10% of patients. BAL cytology should be part of the diagnostic wok up in HM patients with suspected IPA.Disclosures All authors: No reported disclosures.

Aspergillus and progression of lung disease in children with cystic fibrosis

BackgroundThe impact of Aspergillus on lung disease in young children with cystic fibrosis is uncertain.AimsTo determine if positive respiratory cultures of Aspergillus species are associated with: (1) increased structural lung...

DISSEMINATED PULMONARY HISTOPLASMOSIS IN IMMUNOCOMPETENT PATIENTS: A COMMON EPIDEMIOLOGICAL EXPOSURE IN CONSTRUCTION WORKERS

SESSION TITLE: Chest Infections 4 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Most histoplasmosis infections in immunocompetent patients are asymptomatic and self-limited. The following are four immunocompetent patients with a common epidemiologic exposure--construction work---that presented with disseminated pulmonary histoplasmosis and acute respiratory failure. CASE PRESENTATION: The first three cases involved 19, 44 and 70-year-old males presenting with fevers, severe dyspnea and productive cough over 2 weeks after remodeling a same old apartment building. Diffuse crackles were heard on lung auscultation. Chest X-rays and CT chests showed bilateral diffuse lung nodules and alveolar opacities. Patients failed antibiotic therapy and was transferred from a local hospital due to worsening respiratory status. The 19-year-old patient was the first admitted to the ICU. Initially, patient was diagnosed with severe community acquired pneumonia and treated with vancomycin and piperacillin-tazobactam. However, given worsening conditions and history of recent construction work, acute pulmonary histoplasmosis was suspected. Patient was started on empiric amphotericin B and systemic corticosteroid. The 44 and 70-year-old patients were later transferred and started on same antifungal therapy given same exposure. Later, histoplasmosis was confirmed with positive bronchoalveolar lavage (BAL) cultures and urine/serum/BAL Histoplasma antigen. The last case was a 48-year-old male presenting with similar symptoms, physical exam, and chest x-ray and CT chest findings as above. Given his recent work remodeling an old building, patient was empirically started on itraconazole and systemic prednisone. Histoplasmosis was later confirmed with positive BAL/sputum cultures and urine/serum Histoplasma antigen. All four patients recovered with 12 weeks of antifungal therapy. DISCUSSION: Patients most likely developed disseminated pulmonary histoplasmosis due to high level of fungal inoculum from construction work in old buildings. Diagnosis of histoplasmosis is often challenging because (1) clinical presentation resembles bacterial or mycobacterial infections, or inflammatory conditions, (2) diagnosis is confirmed through isolation of the fungus in cultures which take several weeks or histopathology that is invasive. Detection of Histoplasma antigen or Histoplasma antibodies aids in diagnosis but also limited by long turnaround time, low sensitivity and cross reactivity with other mycosis. Misdiagnosis often leads to inappropriate therapy with unnecessary antibiotics or immunosuppressive agents and delay in appropriate antifungal therapy. CONCLUSIONS: It is important to recognize any epidemiologic exposure (construction work, traveling, hiking, farming) for histoplasmosis, promptly start a diagnostic work-up and have a low threshold to start empiric antifungal therapy. Also, workers with potential exposure to bat/bird droppings should be educated on use of N95 respirator as recommended by NIOSH. Reference #1: Benedict K, Mody RK. Epidemiology of Histoplasmosis Outbreaks, United States, 1938-2013. Emerg Infect Dis. 2016;22(3):370-8. Reference #2: Azar MM, Zhang X, Assi R, Hage C, Wheat LJ, Malinis MF. Clinical and epidemiological characterization of histoplasmosis cases in a nonendemic area, Connecticut, United States. Med Mycol. 2017. Reference #3: Wheat LJ, Azar MM, Bahr NC, Spec A, Relich RF, Hage C. Histoplasmosis. Infect Dis Clin North Am. 2016;30(1):207-27. DISCLOSURES: No relevant relationships by Swan Lee, source=Web Response No relevant relationships by Rolando Sanchez, source=Web Response

Bronchoscopic and histologic findings during lymphatic intervention for plastic bronchitis

Percutaneous lymphatic intervention (PCL) is a promising new therapy for plastic bronchitis (PB). We characterized bronchoalveolar lavage (BAL) and cast morphology in surgically repaired congenital heart disease (CHD) patients with PB during PCL. We quantified respiratory and bronchoscopic characteristics and correlated them with post-intervention respiratory outcomes. We retrospectively reviewed patients with PB and surgically repaired CHD undergoing PCL and bronchoscopy at our institution. Pre-intervention characteristics, bronchoscopy notes, BAL cell counts, virology, and cultures were collected. A pathologist blinded to clinical data reviewed cast specimens. Respiratory outcomes were evaluated through standardized telephone questionnaire. Sixty-two patients were included with a median follow-up of 20 months. No patients experienced airway bleeding, obstruction, or prolonged intubation related to bronchoscopy. Of BAL infectious studies, the positive results were 4 (8%) fungal, 6 (11%) bacterial, and 6 (14%) viral. Median BAL count per 100 cells for neutrophils, lymphocytes, and eosinophils were 13, 10, and 0, respectively. Of 23 bronchial casts analyzed, all contained lymphocytes, and 19 (83%) were proteinaceous, with 14 containing neutrophils and/or eosinophils. Median BAL neutrophil count was greater in patients with proteinaceous neutrophilic or eosinophilic casts compared to casts without neutrophils or lymphocytes (P = 0.030). Post-intervention, there was a significant reduction in respiratory medications and support and casting frequency. The predominance of neutrophilic proteinaceous casts and high percentage of positive BAL infectious studies support short-term fibrinolytic and anti-infective therapies in PB in select patients. Flexible bronchoscopy enables safe assessment of cast burden. PCL effectively treats PB and reduces respiratory therapies.