Sarah P. Hammond

Molecular Methods To Improve Diagnosis and Identification of Mucormycosis

ABSTRACT Mucormycosis is difficult to diagnose. Samples from suspected cases often fail to grow Mucorales in microbiologic cultures. We identified all hematologic malignancy and stem cell transplant patients diagnosed with proven mucormycosis between 2001 and 2009 at Brigham and Womens Hospital/Dana-Farber Cancer Institute. Seminested PCR targeting Mucorales 18S ribosomal DNA and sequencing were performed on formalin-fixed paraffin-embedded tissue samples. Of 29 cases of mucormycosis, 27 had tissue samples available for PCR and sequencing. Mucorales PCR was positive in 22. Among 12 culture-positive cases, 10 were PCR positive and sequencing was concordant with culture results to the genus level in 9. Among 15 culture-negative cases, PCR was positive and sequencing allowed genus identification in 12. Mucorales PCR is useful for confirmation of the diagnosis of mucormycosis and for further characterization of the infection in cases where cultures are negative.

Hepatitis B Virus Reactivation following Allogeneic Hematopoietic Stem Cell Transplantation

Reactivation of resolved hepatitis B virus (HBV) infection has been reported in allogeneic hematopoetic stem cell transplantation (HSCT) recipients, but its epidemiology is not well characterized. We performed a retrospective assessment of the timing and risk factors of HBV reactivation among patients with resolved HBV infection undergoing allogeneic HSCT between January 2000 and March 2008. HBV reactivation was defined as development of positive hepatitis B surface antigen after transplant. Among the 61 patients with resolved HBV infection before transplant (hepatitis B core antibody-positive, hepatitis B surface antigen-negative), 12 (19.7%) developed HBV reactivation. The cumulative probability of HBV reactivation 1, 2, and 4 years after transplant was 9.0%, 21.7%, and 42.9%, respectively. In a time-dependent Cox model, the adjusted hazard ratio (HR) of HBV reactivation for patients with pretransplant hepatitis B surface antibody levels <10 milli-international units per milliliter (mIU/mL) was 4.56 (95% confidence interval [CI] 1.23-16.9) compared to those with levels > or =10 mIU/mL; the adjusted HR among patients who developed extensive chronic graft-versus-host disease (cGVHD) was 7.21 (95% CI 1.25-41.5) compared to those who did not. HBV reactivation is a common late complication among allogeneic HSCT recipients with pretransplant resolved infection. Screening for HBV reactivation should be considered for at-risk HSCT recipients. In this cohort, HBV reactivation often developed in patients with cGVHD. Liver biopsy was useful in those patients with both to delineate the contribution of each to liver dysfunction.

Respiratory Virus Detection in Immunocompromised Patients with FilmArray Respiratory Panel Compared to Conventional Methods

ABSTRACT Respiratory virus infections cause significant morbidity and mortality in immunocompromised patients. Timely diagnosis is needed to provide optimal clinical care. Diagnostic tests routinely available at most institutions are limited by poor sensitivity and a slow turnaround time. We collected 90 respiratory samples from 87 immunocompromised patients (56 bronchoalveolar lavage and 34 nasopharyngeal aspirate samples) in order to compare the performance of routine respiratory virus testing available at our institution to the FilmArray respiratory panel assay, a novel diagnostic tool which utilizes multiplex PCR to test for 21 respiratory pathogens with a 1-h turnaround time. Samples with discordant results and 13 samples with concordant results underwent further verification testing by laboratory-developed real-time PCR. The FilmArray assay identified viral pathogens in more samples than did clinical testing (30/90 versus 16/90; McNemar P = 0.001). Most of the additional viral pathogens identified by the FilmArray respiratory panel assay that were confirmed by verification testing were pathogens not assessed by routine clinical tests, including rhinovirus/enterovirus, human metapneumovirus, and coronavirus. The FilmArray respiratory panel assay allowed for increased identification of respiratory viral pathogens in this cohort of immunocompromised patients.

Isavuconazole treatment of a patient with disseminated mucormycosis

ABSTRACT We report a patient with relapsed acute myelogenous leukemia after allogeneic stem cell transplantation who developed disseminated mucormycosis due to Rhizomucor pusillus/R. miehei involving lung, brain, and skin. After failing posaconazole and being intolerant to amphotericin, he was treated effectively with isavuconazole for over 6 months despite ongoing treatment for relapsed leukemia.

Management of Skin and Soft-Tissue Infection — Polling Results

This interactive feature presented the case of a 20-year-old basketball player with acute onset of a red, painful area on his right buttock over the previous 2 days. Readers were invited to vote for one of three possible treatment options.

BK Virus Disease after Allogeneic Stem Cell Transplantation: A Cohort Analysis

The clinical epidemiology of BK virus (BKV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. We evaluated 491 patients transplanted from January 2010 to December 2011 at a single transplant center to assess incidence, severity, and risk factors for BKV disease after HSCT. BKV disease was defined as BKV detection in urine by PCR testing in association with genitourinary symptoms without other concurrent genitourinary conditions. BKV disease occurred in 78 patients (15.9%), for an incidence rate of .47/1000 patient-days (95% confidence interval [CI], .37 to .59); BKV disease was considered severe in 27 patients (5.5%). In multivariate Cox modeling, time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (adjusted hazard ratio [aHR] 4.25; 95% CI, 2.51 to 7.21), cord blood HSCT (aHR 2.28; 95% CI, 1.01 to 5.15), post-transplant mycophenolate use (aHR 3.31; 95% CI, 1.83 to 5.99), and high-dose cyclophosphamide conditioning (aHR 2.34, 95% CI 1.45 to 3.77) were significant predictors of BKV disease. Time-dependent aGVHD grades III to IV (aHR 10.5; 95% CI, 4.44 to 25.0) and cord blood HSCT (aHR 5.40; 95% CI, 1.94 to 15.0) were independent risk factors for severe BKV disease. BKV disease is common and is associated with significant and prolonged morbidity after HSCT. Prospective studies are needed to better define the morbidity of post-HSCT BKV disease and inform the design of prophylaxis and treatment trials.

Invasive fungal disease in patients treated for newly diagnosed acute leukemia

Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients undergoing treatment for acute leukemia (AL). Antifungal prophylactic strategies are associated with significant toxicities and cost. We performed a retrospective study of the incidence and risk factors for IFD among patients newly diagnosed with and treated for AL between January 1, 2004 and July 1, 2006. Patient follow up concluded January 1, 2007. Among 231 patients with newly diagnosed AL, 31 (13.4%) developed IFD by the end of follow up, 24 (10.4%) of whom developed IFD within the first 100 days after diagnosis of AL. The cumulative probability of developing IFD was 5.9% by 30 days and 11.1% at 100 days after AL diagnosis. Patients who had persistent leukemia after an initial course of induction chemotherapy were significantly more likely to develop IFD than those who did not have evidence of persistent leukemia (14/65 (21.5%) vs. 15/148 (10.1%), P = 0.03). In a time‐dependent Cox model, the adjusted hazard ratio for developing IFD within the first 100 days of AL diagnosis based on the number of days of neutropenia in that period was 4.85 (95% confidence interval: 1.52, 15.4). Those patients with more days of neutropenia in the first 100 days after AL diagnosis, such as those who did not achieve remission after a first course of induction chemotherapy, were more likely to develop IFD. Am. J. Hematol., 2010.

Infections Following Facial Composite Tissue Allotransplantation—Single Center Experience and Review of the Literature

We reviewed medical records of all patients (n = 4) who underwent facial composite tissue allotransplantation (FCTA) at our center between April 2009 and May 2011; data were censored in June 2012. We searched for FCTA publications and reviewed them for infectious complications and prophylaxis strategies.

Mortality in hematologic malignancy and hematopoietic stem cell transplant patients with mucormycosis, 2001 to 2009.

ABSTRACT Mortality due to mucormycosis is high. We assessed clinical characteristics and mortality among stem cell transplant and hematologic malignancy patients diagnosed with mucormycosis from 2001 to 2009. Thirty patients were diagnosed with probable or proven mucormycosis during the study. Twenty-six were diagnosed premortem, and most were treated with liposomal amphotericin B single-agent antifungal therapy initially. While the initial antifungal and surgical treatment approach remained stable throughout the study period, 6-week mortality significantly declined over time (67% in 2001 to 2003 versus 45% in 2004 to 2006 versus 20% in 2007 to 2009 [P = 0.04]), as did 12-week mortality (78% in 2001 to 2003 versus 55% in 2004 to 2006 versus 20% in 2007 to 2009 [P = 0.01]).

Cytomegalovirus disease in lung transplantation: impact of recipient seropositivity and duration of antiviral prophylaxis

A recent randomized trial demonstrated that 1 year of antiviral prophylaxis for cytomegalovirus (CMV) after lung transplantation is superior to 3 months of treatment for prevention of CMV disease. However, it is uncertain if a shorter duration of prophylaxis might result in a similar rate of CMV disease among select lung transplant (LT) recipients who are at lower risk for CMV disease, based on baseline donor (D) and recipient (R) CMV serologies.