Steve Gordon

Histoplasmosis in solid organ transplant recipients: 10 years of experience at a large transplant center in an endemic area

BACKGROUND Many clinical scenarios have been encountered by patients who developed histoplasmosis after receiving a solid organ transplant at a large transplant center in an endemic area. METHODS Cases of posttransplantation histoplasmosis were identified by use of multiple methods, including reviews of microbiology test results, transplant databases, and billing codes. Data were obtained retrospectively. Descriptive statistics were used. RESULTS During the 1997-2007 study period, 3436 patients received a solid organ transplant, and 38 patients were identified as having posttransplantation histoplasmosis. Of these 38 patients, 9 were excluded from our study because the diagnosis was solely clinical. Of the remaining 29 patients, 14 had posttransplantation histoplasmosis (incidence, 1 case per 1000 person-years); 14 showed histologic evidence of histoplasmosis in the recipient or donor tissue, which was encountered unexpectedly at the time of transplantation; and 1 had histoplasmosis before receiving the transplant. Of the 14 patients who developed histoplasmosis after transplantation, 5 were heart transplant recipients, 3 were lung transplant recipients, 3 were kidney transplant recipients, 1 was a liver transplant recipient, 1 was a pancreas transplant recipient, and 1 was a kidney-pancreas transplant recipient. The median time from transplantation to diagnosis was 17 months (interquartile range, 8.1-46 months), and the median time from onset of symptoms to diagnosis 3 weeks (interquartile range, 1.9-6.5 weeks). All recipients had disseminated disease. The most common treatment was amphotericin B and itraconazole. All were cured, or still on treatment, but symptom-free. Of the 14 patients who had an explanted organ or donor tissue that showed histologic evidence of histoplasmosis, 13 (93%) were lung transplant recipients, and 1 (7%) was a liver transplant recipient. None of these patients developed active histoplasmosis, but all received prophylactic treatment. Finally, 1 patient had histoplasmosis before transplantation; he was treated with itraconazole 3 months before and after transplantation, and he did well. CONCLUSIONS In conclusion, posttransplantation histoplasmosis is rare (1 case per 1000 transplant-person-years; 95% confidence interval, 0.6-1.7), even in endemic areas. Prognosis is good but requires protracted therapy. Patients with latent infection did not develop posttransplantation histoplasmosis when prophylaxis was used.

Detection of Legionella pneumophila by Real-Time PCR for the mip Gene

ABSTRACT A real-time PCR assay for the mip gene of Legionella pneumophila was tested with 27 isolates of L. pneumophila, 20 isolates of 14 other Legionella species, and 103 non-Legionella bacteria. Eight culture-positive and 40 culture-negative clinical specimens were tested. This assay was 100% sensitive and 100% specific for L. pneumophila.

Challenges of Interferon-γ Release Assay Conversions in Serial Testing of Health-care Workers in a TB Control Program

BACKGROUND Clinical data with use of serial interferon-γ release assay (IGRA) testing in US health-care workers (HCWs) are limited. METHODS A single-center, retrospective chart review was done from 2007 to 2010 of HCWs who underwent preemployment QuantiFERON-TB Gold In-Tube testing. Demographic data, bacille Calmette-Guérin history, prior tuberculin skin test result if done, and baseline and serial IGRA values were obtained. The number of IGRA converters and reverters and their subsequent management by infectious disease physicians were reviewed. Quantitative IGRA-negative values were not available. RESULTS A total of 7,374 IGRAs were performed on newly hired HCWs. Of these tests, 486 (6.6%) were positive at baseline, 305 (4.1%) were indeterminate, and 6,583 (89.3%) were negative. From 2007 to 2010, 52 of 1,857 HCWs (2.8%) with serial IGRA tests were identified as converters, with a serial IGRA median value of 0.63 IU/mL. Seventy-one percent of HCWs with IGRA conversion had values ≤ 1 IU/mL. None of the converters had active TB or were part of an outbreak investigation. CONCLUSIONS Clinical significance of most QuantiFERON-TB Gold In-Tube conversions in serial testing remains a challenging task for clinicians. The use of a single cutoff point criterion for IGRA may lead to overdiagnosis of new TB infections. Clinical assessment and evaluation may help to prevent unnecessary therapy in these cases. The criteria for defining conversions and reversions by establishing new cutoffs needs to be evaluated further, especially in HCWs.

Clinical characteristics of 13 solid organ transplant recipients with ganciclovir‐resistant cytomegalovirus infection

Abstract: Background. Ganciclovir‐resistant (GCV‐R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients. Objective. To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV‐R CMV seen between 1990 and 2000 at a single center. Methods. Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV‐R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data. Results. Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R–), and 11/13 (85%) had tissue‐invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV‐based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3×/week) IV ganciclovir for prophylaxis. Conclusions. GCV‐R CMV is associated with CMV D+/R– status, tissue‐invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV‐R CMV.

Relapsing Exophiala jeanselmei phaeohyphomycosis in a lung-transplant patient

Abstract: Dematiaceous fungi are a cause of a variety of human infections, including phaeohyphomycosis, that may affect patients with solid organ or bone marrow transplants. Exophiala jeanselmei, the most common cause of the pheomycotic cyst/subcutaneous phaeohyphomycosis in the United States, has been shown to cause disease in transplant recipients. We report a lung‐transplant patient with relapsing and invasive E. jeanselmei phaeohyphomycosis, who previously had a pheomycotic cyst excised and treated with oral fluconazole. The patient was subsequently treated with re‐excision and an 8‐month course of oral itraconazole without relapse as to date.

Effect of the influenza A (H1N1) live attenuated intranasal vaccine on nitric oxide (FENO) and other volatiles in exhaled breath

For the 2009 influenza A (H1N1) pandemic, vaccination and infection control were the main modes of prevention. A live attenuated H1N1 vaccine mimics natural infection and works by evoking a host immune response, but currently there are no easy methods to measure such a response. To determine if an immune response could be measured in exhaled breath, exhaled nitric oxide (FE(NO)) and other exhaled breath volatiles using selected ion flow tube mass spectrometry (SIFT-MS) were measured before and daily for seven days after administering the H1N1 2009 monovalent live intranasal vaccine (FluMist®, MedImmune LLC) in nine healthy healthcare workers (age 35 ± 7 years; five females). On day 3 after H1N1 FluMist® administration there were increases in FE(NO) (MEAN±SEM: day 0 15 ± 3 ppb, day 3 19 ± 3 ppb; p < 0.001) and breath isoprene (MEAN±SEM: day 0 59 ± 15 ppb, day 3 99 ± 17 ppb; p = 0.02). MS analysis identified the greatest number of changes in exhaled breath on day 3 with 137 product ion masses that changed from baseline. The exhaled breath changes on day 3 after H1N1 vaccination may reflect the underlying host immune response. However, further work to elucidate the sources of the exhaled breath changes is necessary.

COMPARISON OF NON-SURGICAL AND SURGICAL THERAPY FOR PROSTHETIC VALVE ENDOCARDITIS: A PROPENSITY SCORE-ADJUSTED STUDY

Background: Patients with prosthetic valve endocarditis (PVE) who are not treated surgically have poor clinical outcomes. This study was undertaken to compare outcomes of non-surgical with surgical treatment for PVE. Methods: Patients admitted to Cleveland Clinic with PVE from April 1, 2008 to

ETIOLOGY, PATIENT CHARACTERISTICS AND SURGICAL OUTCOMES OF ACUTE SEVERE AORTIC REGURGITATION

Background: Acute severe aortic regurgitation (AAR) is an uncommon etiology of hemodynamic instability requiring urgent surgical intervention. We sought to describe its etiology, patient characteristics and surgical outcomes in a large tertiary referral center. Methods: All patients (pts) admitted

YIELD OF TRANSESOPHAGEAL ECHOCARDIOGRAPHY TO DETECT INVASIVE COMPLICATIONS OF AORTIC PROSTHETIC VALVE ENDOCARDITIS

The correlation of transesophageal echocardiography (TEE) with surgical findings in patients with invasive complications of aortic prosthetic valve endocarditis (PVE) is uncertain. We therefore assessed the performance of TEE to detect invasive complications when compared to anatomic findings. We

PREDICTORS AND PROGNOSTIC SIGNIFICANCE OF ACUTE KIDNEY DYSFUNCTION IN PATIENTS WITH INFECTIVE ENDOCARDITIS

Renal dysfunction occurs in 1/3 of patients with infective endocarditis (IE) and is associated with increased mortality. Underlying sepsis and exposure to nephrotoxic agents may be contributory. We sought to identify independent predictors of acute kidney dysfunction (AKD) in this population. We