Noroviral diarrhea in solid organ transplant recipients: An analysis of interventions and outcomes.

INTRODUCTION: Noroviral infection can lead to chronic diarrhea in solid organ transplant (SOT) recipients with significant morbidity and mortality. Existing literature has described a wide spectrum of illness and has not come to a consensus on the optimal management of this condition. METHODS: We undertook a retrospective review of all adult SOT recipients between 1/1/2018 and 12/31/2020 who were diagnosed with their first episode of noroviral diarrhea (NVD). Demographic, clinical interventions, and outcomes within 6 months of diagnosis were recorded. Patients' outcomes were classified as either resolved, improved or persistent at 6 months. RESULTS: Seventy-nine SOT recipients were included. Thirty-eight patients (48%) had chronic diarrhea at baseline (CDB). Thirty-two patients (40%) received nitazoxanide, 28 patients (35%) had their immunosuppression adjusted and seven patients (9%) received intravenous immunoglobulin. Diarrhea improved or resolved in 68 patients (85%). Improvement or resolution of diarrhea was observed in 98% of those who did not have history of chronic diarrhea versus 74% in those who did (p = .002). NVD improved in all 12 patients who had mycophenolate discontinued, although this was not statistically significant (p = .131). CONCLUSION: CDB was associated with worse outcomes regardless of intervention. A low threshold to test for NVD in SOT recipients with chronic diarrhea is prudent to prevent delayed diagnosis.

A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients.

The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use, and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers, and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.

(1,3) ß-D-Glucan in Bronchoalveolar Lavage of Lung Transplant Recipients for the Diagnosis of Invasive Pulmonary Aspergillosis.

(1,3) ß-D-Glucan (BDG) is present in the cell wall of most fungi. Its detection in serum has been useful in the diagnosis of invasive aspergillosis (IA) in patients with hematologic malignancies. However, assaying for BDG did not perform well in the serum of lung transplant recipients. We undertook to study the performance of BDG in the bronchoalveolar lavage (BAL) of lung transplant recipients for the diagnosis of invasive pulmonary aspergillosis (IPA). Available and stored BAL samples from lung transplant recipients at the Toronto General Hospital between October 2007 and April 2013 were tested for BDG using the Fungitell kit from the Associates of Cape Cod Inc, Falmouth, MA, USA : The International Society for Heart and Lung transplantation (ISHLT) criteria was used for the diagnosis of IA. Of 195 samples, there were ten episodes of IA. The sensitivity and specificity of the test were 80% and 53% and 60% and 70% at 41 pg/ml and 108 pg/ml cut-offs, respectively. On excluding 52 bronchoscopies due to receipt of anti-Aspergillus therapy during specimen collection, the sensitivity and specificity improved to 75% and 91%, respectively, at a 524 pg/ml cut-off. However, only four episodes of IA remained in this analysis. Using BDG in BAL of lung transplant recipients for the diagnosis of IA, our study demonstrated moderate sensitivity and specificity.

Mold infections in lung transplant recipients.

Fungal infections continue to produce morbidity and mortality in lung transplant recipients despite the widespread use of antifungal prophylaxis. There has been a decline in Candida infections but Aspergillus species predominate. Other mold pathogens including Fusarium, Scedosporium, and Zygomycetes also cause infections in lung transplant recipients. Furthermore, the widespread use of antifungal prophylaxis has prompted a delay in onset of Aspergillus infection in lung transplant recipients. Pulmonary parenchymal disease has become the most common manifestation of invasive aspergillosis. Among the risk factors pre- or posttransplant Aspergillus colonization is the most important risk factor reported in several retrospective studies. Recently posttransplant colonization has been implicated in the development of bronchiolitis obliterans syndrome. Other factors that have been reported include preceding cytomegalovirus infections, hypogammaglobulinemia, and single-lung transplantation. The risk factors for other mold infections such as Scedosporium, Fusarium, and Zygomycetes are not well studied. The best antimold prophylaxis strategy and choice of drug remains to be elucidated. Most lung transplant centers use either voriconazole or inhaled amphotericin preparations. However, data have emerged regarding the increased risk of squamous cell cancer in lung transplant recipients on voriconazole prophylaxis. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in a significant decrease in mortality.

A strategy for prevention of fungal infections in lung transplantation: Role of bronchoalveolar lavage fluid galactomannan and fungal culture.

BACKGROUND: The optimal strategy for prevention of invasive fungal infections in lung transplant recipients remains undetermined. We studied strategies based on bronchoalveolar lavage fungal culture and galactomannan for prevention of invasive aspergillosis in lung transplant recipients. METHODS: Consecutive lung transplant recipients were evaluated during the period January 2010 to September 2014. Rates of invasive aspergillosis and all-cause mortality were recorded at 1 year. Criteria established by the International Society for Heart and Lung Transplantation were used to define invasive fungal infections. Multivariate Cox regression analyses were performed to assess the outcomes of mortality and invasive aspergillosis. RESULTS: A total of 519 lung transplant recipients with 3,077 bronchoscopies were included in our study. The cumulative incidence of fungal infections was 14% (75 of 519). Of these patients, 10.6% (54 of 519) developed Aspergillus-related clinical syndromes. Using multivariate analysis, pre-emptive therapy was associated with significantly lower rates of invasive aspergillosis at 1 year post-transplantation compared with no pre-emptive therapy (hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.09 to 0.58). Pre-emptive therapy and invasive aspergillosis had similar mortality rates compared with no invasive aspergillosis, or negative culture and galactomannan at 1 year (HR 0.54, 95% CI 0.23 to 1.28; and HR 0.99, 95% CI 0.44 to 2.25, respectively). During follow-up, 50% (259 of 519) of patients were negative for galactomannan and Aspergillus culture in bronchoalveolar lavage, and did not receive anti-fungal treatment. Only 2 patients developed invasive aspergillosis in this cohort. CONCLUSIONS: Our study suggests that use of bronchoalveolar lavage culture and a galactomannan-directed pre-emptive approach significantly decreased the risk of invasive aspergillosis, allowing a 50% reduction in anti-fungal exposure compared with a universal prophylaxis approach, without affecting mortality at 1 year.

Pentraxin 3 levels in bronchoalveolar lavage fluid of lung transplant recipients with invasive aspergillosis.

BACKGROUND: Invasive aspergillosis is the most common invasive fungal infection in lung transplant recipients. The use of galactomannan testing in bronchoalveolar lavage (BAL) fluid has improved diagnosis of invasive aspergillosis; however, false-positive results can lead to overdiagnosis and unnecessary treatment. The use of proinflammatory markers such as pentraxin 3 (PTX3) may help differentiate between Aspergillus colonization and disease. METHODS: BAL PTX3 concentrations were measured by enzyme-linked immunosorbent assay in 151 lung transplant recipients and 9 healthy control subjects. Patients were characterized as having Aspergillus colonization or invasive disease according to International Society of Heart and Lung Transplantation criteria. Concomitant PTX3values were compared using Mann-Whitney U and Kruskal-Wallis tests. RESULTS: We analyzed 322 BAL stored samples and identified 15 invasive aspergillosis events, 38 Aspergillus colonizations, and 17 positive galactomannan with negative Aspergillus cultures. Median BAL PTX3 level was significantly higher in patients with invasive aspergillosis compared with patients with Aspergillus colonization and healthy control subjects (439.20 pg/ml [interquartile range (IQR) 168.18-778.90], 68.93 pg/ml [IQR 13.67-156.74], and 13.67 pg/ml [IQR 13.67-121.18]; p < 0.001). Patients with BAL PTX3 value >319 pg/ml with positive galactomannan and patients with BAL PTX3 value >312 pg/ml with positive Aspergillus culture were 4.5 and 5.5 times more likely to have invasive pulmonary aspergillosis, respectively. CONCLUSIONS: Our study shows that PTX3 measurements in BAL samples were significantly higher among patients with invasive aspergillosis and may help to identify patients with Aspergillus colonization and false-positive galactomannan in BAL samples.

Trichosporon loubieri Fungemia in a 39-Year-Old Caucasian Woman With B-Cell Lymphoblastic Leukemia.

We report a case of Trichosporon loubieri (T. loubieri) fungemia with likely liver involvement in a 39-year-old Caucasian patient with relapsed B-cell acute lymphoblastic leukemia after an allogeneic hematopoietic cell transplant. This is the fifth published case of T. loubieri infection and only the third case of T. loubieri fungemia, to our knowledge. All 3 cases of T. loubieri infection with fungemia had liver involvement.

Surveillance of patients identified with fungal mold at a public academic medical center.

BACKGROUND: This study describes the epidemiology of patients with fungal mold infection or colonization at a large academic medical center during a period of ongoing construction of a new hospital building. METHODS: This is an observational retrospective cohort study performed at a public academic hospital. We performed focused medical record review of all patients with fungal mold isolated on microbiologic culture over a 3-year period from May 2009 through April 2012. We established case definitions by modifying criteria used in previously published studies. We established 4 categories for invasiveness: proven invasive fungal disease (IFD), probable IFD, clinical infection not meeting IFD criteria, or colonization/contamination. We also established 3 categories for association with our health care facilities: health care-associated hospital onset (HO), health care-associated community onset (HACO), or community associated (CA). RESULTS: Of the 188 cases included in the study, 15 (7.9%) and 23 (12.2%) met criteria for proven and probable IFD, respectively. Of the cases, 114 (60.6%) represented contamination or colonization, and 36 (19.1%) had clinical infection not meeting IFD criteria. Epidemiologically, 46 (24.5%) cases were HO, 42 (22.3%) cases were HACO, and 100 (53.2%) cases were CA. CONCLUSION: The surveillance methods we established were helpful for characterizing and monitoring fungal mold infections at the study institution.

Anti-Aspergillus Prophylaxis in Lung Transplantation: A Systematic Review and Meta-analysis.

Aspergillus is the most common cause of invasive fungal infection in lung transplant recipients. Most transplant centers employ routine antifungal prophylaxis to prevent the development of invasive aspergillosis (IA). We identified 22 studies from the literature to perform a systematic review and meta-analysis, in order to assess the development of IA and Aspergillus colonization with and without antifungal prophylaxis. Similarly, differences in the toxicities of different formulations of amphotericin-B and azoles were analyzed. Nineteen of 235 (8.1 %) and 28 of 196 (14.3 %) developed IA in the universal prophylaxis and no-prophylaxis arms, respectively (RR: 0.36, CI: 0.05-2.62). We did not find a significant reduction in IA or Aspergillus colonization with universal anti-aspergillus prophylaxis. There was no difference in the adverse events of inhaled amphotericin-B deoxycholate and lipid formulations of inhaled amphotericin-B. However, voriconazole was more hepatotoxic than itraconazole. These results should be interpreted with caution due to heterogeneity of the studies. A multicenter randomized controlled trial is warranted to assess the efficacy of anti-aspergillus prophylaxis in lung transplant recipients.

Interpretation of positive molecular tests of common viruses in the cerebrospinal fluid.

Many central nervous system infections are historically difficult to diagnose. Polymerase chain reaction (PCR) has revolutionized the diagnosis of these infections because of their high sensitivity despite the lack of data on clinical usefulness. We conducted a retrospective study that included patients with positive cerebrospinal fluid (CSF) PCR for herpes simplex virus, varicella-zoster virus, JC virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) between January 2009 and December 2011. The positive results were grouped into definite, likely, and possible true positives and likely false-positive categories based on pre-specified definitions specific to each virus. Of 1663 CSF viral PCR tests, 88 were positive (5%). The combined positive predictive value (PPV) was 58%. The PPVs were least for CMV and EBV at 29 and 37%, respectively. A positive CSF viral PCR result has to be interpreted with caution due to several false-positive results.

Antimicrobial stewardship at transition of care from hospital to community.

Mandatory infectious disease consultation for parenteral antimicrobials at hospital discharge resulted in avoiding postdischarge parenteral antimicrobials in 28% of patients. No emergency department visit or rehospitalization within 30 days for these patients was a consequence of parenteral antimicrobial avoidance. Antimicrobial stewardship at transition of care is effective in reducing unnecessary antimicrobial use.

Contribution of infectious disease consultation toward the care of inpatients being considered for community-based parenteral anti-infective therapy.

BACKGROUND: In the acute care setting in a multidisciplinary healthcare environment, the contribution of infectious disease (ID) specialists to overall patient care is difficult to measure. This study attempts to quantify the contribution of ID specialists when consulted for an activity specific to ID practice, community-based parenteral anti-infective therapy (CoPAT). METHODS: In February 2010, an electronic form for requesting ID consultations was introduced in the computerized provider order entry (CPOE) system at the Cleveland Clinic. This allowed for easy identification of ID consultations for CoPAT. Hospital records for all patients with CoPAT consultation requests between February 11, 2010 and May 15, 2010 were reviewed for specific defined contributions in the domains of optimization of antimicrobial therapy, significant change in patient assessment, and additional medical care contribution. RESULTS: Over a 3-month period, there were 263 CoPAT consultation requests via CPOE, of which 172 were initial consultations and 91 reconsultations. Antimicrobial treatment was optimized in 84%, a significant change in patient assessment made in 52%, and additional medical care contribution provided in 71% of consultations. In 33% of consultations, there was contribution in all 3 domains. CoPAT was deemed not to be necessary in 27%. For patients requiring CoPAT, effective care transition from the inpatient to outpatient setting was assured at least 86% of the time. CONCLUSION: Infectious disease consultation before discharge on parenteral antibiotics adds value by contributing substantially to inpatient care, and providing antimicrobial stewardship and continuity of care at a critical patient care transition point.

Nephrogenic systemic fibrosis following acute kidney injury and exposure to gadolinium.

Nephrogenic systemic fibrosis (NSF) is a scleroderma-like systemic fibrosing condition of unknown etiology described in patients with renal insufficiency. Gadolinium exposure has been strongly associated with the development of NSF though the mechanism of such injury is not known. There are only few reported cases of NSF in the setting of acute renal failure and fewer reported cases where skin lesions developed after kidney function had returned to normal. We report a case of NSF in a young Hispanic woman with lupus nephritis but normal creatinine, who received gadolinium during a brief episode of prerenal acute kidney injury not requiring dialysis, secondary to sepsis.

Heart Disease in Patients with HIV/AIDS-An Emerging Clinical Problem.

HIV/AIDS (Human immunodeficiency virus/ Acquired immuno deficiency syndrome) is a growing global problem, in terms of its incidence and mortality. Patients with HIV/AIDS are living much longer with HAART (Highly active antiretroviral therapy) therapy so much so that HIV/AIDS has now become a part of the chronic disease burden, like hypertension and diabetes. Patients with HIV/AIDS and symptoms suggestive of cardiac disease represent a diagnostic and therapeutic challenge in clinical practice; Cardiologists are more frequently encountering this problem. An algorithmic, anatomic approach to diagnosis, localizing disease to the endocardium, myocardium and pericardium can be useful. An intimate knowledge of opportunistic infections affecting the heart, effects of HAART therapy and therapy for opportunistic infections on the heart is needed to be able to formulate a differential diagnosis. Effects of HAART therapy, especially protease inhibitors on lipid and glucose metabolism, and their influence on progression to premature vascular disease require consideration. Treatment of cardiac disease, in HIV/AIDS patients can vary from non-HIV patients, based on drug interactions, differences in responsiveness, and other factors; and this area requires further research.