#11: Metronidazole for the Treatment of Norovirus in Transplant Recipients

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S2-S3
Author(s):  
Maulin Soneji ◽  
Alexander M Newman ◽  
Jacquie Toia ◽  
William J Muller
Keyword(s):  
Clinical Improvement ◽  
Rescue Therapy ◽  
Bacterial Flora ◽  
Laboratory Data ◽  
Mtor Inhibitors ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Giardia Infection ◽  
Norovirus Gastroenteritis

Abstract Background Norovirus is a common cause of gastroenteritis in both immunocompetent and immunocompromised hosts. In transplant recipients, it can lead to prolonged shedding and chronic diarrhea. Treatment with nitazoxanide, oral immunoglobulin, or mammalian target of rapamycin (mTOR) inhibitors have shown varying degrees of benefit in small studies. The commensal gastrointestinal bacterial flora may influence the pathogenesis of norovirus infection. Metronidazole is often used to modulate gastrointestinal flora, and improvement of an HIV patient with suspected Giardia infection subsequently identified to have norovirus suggested a possible use of this drug for other immune-suppressed patients with norovirus infection. Methods Solid-organ or stem cell transplant recipients testing positive for norovirus in stool from July 2014 to March 2019 were identified from the medical record. Patient characteristics, laboratory data, and medications were systematically reviewed to identify factors associated with clinical improvement. Results Thirty-eight patients met inclusion criteria. Almost 75% of the patients were male. Almost 80% of the patients were solid-organ transplant recipients: 40% heart, 24% kidney, and 15% liver. There were 85 positive norovirus tests among the 38 patients. Of these, 14 involved coinfections with another potential pathogen: 11 with adenovirus, 2 with Clostridioides difficile, and 1 with cytomegalovirus. In 25 of the 85 positive norovirus tests, nitazoxanide was given. Clinical improvement was documented in 15 of these episodes (60%), while no improvement was observed in 10 (40%). Eight positive tests were treated with metronidazole alone, with documented improvement observed during 6 (75%) courses. In 9 additional episodes, metronidazole was given within a week of the test result and 2 of these had improvement. When other antibiotics were used concurrently with metronidazole, 78% of episodes (7/9) did not lead to clinical response. Changes in immunosuppression were used for the treatment of 6 episodes, leading to clinical improvement in 5. Conclusion Metronidazole treatment was associated with clinical improvement of norovirus gastroenteritis in transplant recipients at rates similar to those seen with nitazoxanide therapy. Reduction in immunosuppression also led to clinical improvement but in situations where that cannot be done safely, metronidazole may be an alternative to nitazoxanide. In this cohort, metronidazole was only used as a therapy after nitazoxanide, suggesting that a trial of metronidazole as rescue therapy in comparison to a repeat course of nitazoxanide after the initial failure of nitazoxanide is justified.

Greater Susceptibility for Metabolic Syndrome in Pediatric Solid Organ and Stem Cell Transplant Recipients

2019 ◽  
Vol 103 (11) ◽  
pp. 2423-2433
Author(s):  
Ricarda Blöte ◽  
Nima Memaran ◽  
Bianca Borchert-Mörlins ◽  
Daniela Thurn-Valsassina ◽  
Imeke Goldschmidt ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients

scholarly journals Beyond Cytomegalovirus and Epstein-Barr Virus: a Review of Viruses Composing the Blood Virome of Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients

2020 ◽  
Vol 33 (4) ◽  
Author(s):  
Marie-Céline Zanella ◽  
Samuel Cordey ◽  
Laurent Kaiser
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Clinical Significance ◽  
Viral Infections ◽  
Solid Organ Transplantation ◽  
High Morbidity ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem

SUMMARY Viral primary infections and reactivations are common complications in patients after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) and are associated with high morbidity and mortality. Among these patients, viral infections are frequently associated with viremia. Beyond the usual well-known viruses that are part of the routine clinical management of transplant recipients, numerous other viral signatures or genomes can be identified in the blood of these patients. The identification of novel viral species and variants by metagenomic next-generation sequencing has opened up a new field of investigation and new paradigms. Thus, there is a need to thoroughly describe the state of knowledge in this field with a review of all viral infections that should be scrutinized in high-risk populations. Here, we review the eukaryotic DNA and RNA viruses identified in blood, plasma, or serum samples of pediatric and adult SOT/HSCT recipients and the prevalence of their detection, with a particular focus on recently identified viruses and those for which their potential association with disease remains to be investigated, such as members of the Polyomaviridae, Anelloviridae, Flaviviridae, and Astroviridae families. Current knowledge of the clinical significance of these viral infections with associated viremia among transplant recipients is also discussed. To ensure a comprehensive description in these two populations, individuals described as healthy (mostly blood donors) are considered for comparative purposes. The list of viruses that should be on the clinicians’ radar is certainly incomplete and will expand, but the challenge is to identify those of possible clinical significance.

scholarly journals 2571. Norovirus Infection and Gut Microbiota in Transplant Recipients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S893-S893
Author(s):  
Pearlie P Chong ◽  
Pearlie P Chong ◽  
Sarah K Hussain ◽  
Nicole Poulides ◽  
Laura Coughlin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
16S Rrna Gene Sequencing ◽  
Antibiotic Use ◽  
Rrna Gene ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem

Abstract Background In vitro studies have shown that enteric viruses require the gut microbiota (specific members of the Enterobacteriaceae family) for efficient infection of the gastrointestinal tract. Human norovirus (NV) infection in transplant recipients may be chronic and severe. The role of gut microbiota has not been defined in this setting. We hypothesized that gut microbiota diversity and composition are different in norovirus-infected transplant patients. Methods We performed a single-center, pilot, prospective cohort study of adult solid-organ transplant and hematopoietic stem cell transplant recipients with diarrhea. Serial fecal samples were collected and processed for gDNA. Norovirus levels were quantified by PCR and gut microbiota profiling determined by 16S rRNA gene sequencing. Results Twenty-five transplant recipients were included: 9 with NV infection and 16 without. Age (61 ± SEM 2.3 years vs. 54 ± 3.5 years; P = 0.172), duration of diarrhea prior to diagnosis (105 ± 43 days vs. 20 ± 7 days; P = 0.146), prior cumulative antibiotic use (42 ± 12 days vs. 46 ± 17 days; P = 0.646), anti-anaerobic antibiotic use (7 ± 3 days vs. 11 ± 6 days; P = 0.643) and length of hospitalization (12 ± 6 days vs. 12 ± 3 days; P = 0.624) were not different between transplant recipients with and without NV infection. Interestingly, the relative abundance of Enterobactericeae was significantly higher in NV-infected transplant recipients compared with those without NV infection (26 ± 5.8% vs. 6.2 ± 2.8%; P = 0.017, Mann–Whitney) (Figure 1). In contrast, the abundance of the Phyla Bacteroidetes (11.2 ± 5.2% vs. 26.3 ± 6.5%; P = 0.191), and Firmicutes (26.8 ± 7.6% vs. 24.9 ± 4.7%; P = 0.803), were not significantly different between those who were NV and not NV-infected. Of note, the diversity metrics of Shannon (3.5 ± 0.4 vs. 3.8 ± 0.3; P = 0.637) and inverse Simpson indices (1.3 ± 0.1 vs. 1.1±0.1; P = 0.419) were not significantly different between the two groups. Conclusion Norovirus-infected transplant recipients had a significantly higher relative abundance of Enterobactericeae in their gut microbiota compared with transplant recipients without norovirus infection. Future studies are needed to explore if this association is mechanistically important for norovirus infection. Disclosures All authors: No reported disclosures.

scholarly journals 1393. Tuberculosis (TB) After Solid-organ Transplant (SOT) and Hematopoietic Stem Cell Transplant (HSCT)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S506-S506
Author(s):  
Cecilia F Peña-Puga ◽  
Oscar Morado-Aramburo ◽  
Darwin Lambraño-Castillo ◽  
Jennifer Cuellar-Rodríguez
Keyword(s):  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
First Year ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Latent Tb ◽  
Disseminated Disease

Abstract Background Tuberculosis is an important opportunistic infection that affects transplant recipients; the risk of active infection increases significantly when compared with the general population. Most disease results from reactivation of latent infection, being extrapulmonary and disseminated disease the most common presentations. Most cases occur during the first year post-transplantation when immunosuppression is higher. We describe the clinical characteristics of patients diagnosed with TB after transplant. Methods Single-center, retrospective study of adult SOT and HSCT recipients in Mexico City, who developed active TB after transplant. We reviewed medical records, and collected demographic data, clinical characteristics, and outcome. Results We identified 16 patients with post-transplant TB; 13 SOT, and 3 HSCT recipients. The majority of SOT recipients were women (53.8%); median age was 43 years, 9 were kidney and 4 liver transplant recipients. At TB diagnosis, 84.6% of patients were on 3 immunosuppressors. Latent TB was assessed before transplant in 5 patients (38.4%), of these 3 (60%) were tuberculin skin test+, and 2 received isoniazid. Extrapulmonary disease was most common (7, 53.8%). Predominant symptoms were fever (53.8%), chills (30.8%), and diaphoresis (38.5%); six were diagnosed during the 1st year (46.2%) post-transplant; the median of time to diagnosis was 24 months after transplant. The diagnosis was made by histopathology in most cases. Twelve patients received first-line anti-TB treatment. Overall mortality was 30.8%, directly attributable to TB in 2. In the HSCT group, 2 were women; median age was 22 years, 2 allogeneic and 1 autologous transplant. One patient had been treated for latent TB before transplantation. Two developed disseminated disease. Two patients presented within 6 months after the transplant, and the other within a year. Mortality was 100%, attributable to the infection in two patients. Conclusion In regions with intermediate to a high prevalence of TB; post-transplant TB could result from reactivation or post-transplant exposure. Most cases occur within the first year post-transplant; clinical symptoms are nonspecific, which lead to a delay in diagnosis. Morbidity and mortality remains high. Disclosures All authors: No reported disclosures.

Survival outcomes of post-transplant lymphoproliferative disorder: A 12-year analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19543-e19543
Author(s):  
Hira Ghazal Shaikh ◽  
Rafiullah Khan ◽  
Michael Grabel ◽  
Roman Jandarov ◽  
Mahmoud Charif ◽  
...  
Keyword(s):  
Poisson Regression ◽  
Lymphoproliferative Disorder ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Solid Organ ◽  
Cell Transplant ◽  
Annual Income ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Post Transplant

e19543 Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and potentially fatal complication of chronic immunosuppression in solid organ transplant (SOT) and hematopoietic stem cell transplant recipients. With an overall incidence of ̃ 1 percent in the transplant recipients, it is the most common malignancy, with the exception of skin cancer, after SOT in adults. There is a paucity of information concerning the outcomes and prognostic indicators of PTLD. Methods: We queried the National Cancer Database (NCDB) from 2004 – 2015 for patients with diagnosis of PTLD. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier curves to present the cumulative probability of survival. Additionally, Poisson regression was used to test the association between baseline variables and days to event. All statistical analyses were performed using R 4.0.3. Results: Total number of patients identified by inclusion criteria was 425. 1-year OS was 73% (CI 0.684, 0.776), 3-year OS 63% (CI 0.581, 0.683), and 5-year OS 56% (CI 0.502, 0.619) in patients with survival data available (n = 365). 263 patients were excluded due to incomplete data, yielding a final cohort of 192 patients for correlational analysis. The median age was 59 years. Majority were males (60%), < 65 year old (75.5%), Hispanics (91%), and had Charlson-Deyo Comorbidity score of 0 (63.5%). 77% were Caucasians while 15.6% were African Americans. OS was longer in males, Caucasians, patients who received radiation (versus no radiation), those treated at academic or comprehensive cancer center (versus community cancer center), had annual income > $63000 (versus < $63000) by Poisson regression analysis, however the difference was not statistically significant. Conclusions: Our data demonstrates a trend toward poor survival with socioeconomic and treatment variables including gender, race, annual income, treatment center expertise and radiation treatment. Randomized trials are needed to further assess the outcomes of PTLD.

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