Norovirus (NoV) may cause or contribute to chronic diarrhea among immunocompromised hosts. Neither vaccines nor antiviral therapies are available to prevent or treat NoV infection. We conducted a National Institute of Health-sponsored multicenter, prospective, randomized, double-blind study of nitazoxanide (NTZ) for the treatment of NoV-infected adult transplant patients between 2018 and 2021. Subjects with a positive stool NoV polymerase chain reaction within 14 days of enrollment and active gastrointestinal symptoms were randomly assigned (1:1) to NTZ or placebo (P) for 56 consecutive doses and followed for 6 months. The primary endpoint was time to symptom resolution. Secondary endpoints included virologic efficacy and frequency of adverse events. A total of 31 subjects (16 NTZ and 15 P) were enrolled. Most had chronic (≥14 days) symptoms (77%) and were solid organ transplant recipients (30/31). In the intention-to-treat population, the median time to symptom resolution was 19.0 (95% confidence interval, 1.0-31.0) days vs 11.0 (95% confidence interval, 2.0-14.0) days for the NTZ and P groups, respectively (P = .459). Time to first negative stool NoV polymerase chain reaction was not significantly different between treatment arms (P = .873). There were no serious adverse events related to NTZ. NTZ did not shorten the time to symptom resolution or viral shedding. Although safe, NTZ likely contributes little to the management of chronic NoV. ClinicalTrials.gov: NCT03395405 (registration date 2018-01-04).

BACKGROUND: In the phase 3 SOLSTICE study (NCT02931539), maribavir was superior to investigator-assigned therapy (IAT) for confirmed cytomegalovirus viremia clearance at study week 8 in hematopoietic cell/solid organ transplant (HCT/SOT) recipients. We report additional efficacy and safety analyses from the SOT subgroup. METHODS: Eligible SOT recipients (n=211) received maribavir 400 mg twice daily (n=142) or IAT (n=69) for 8 weeks (12 weeks' follow-up). Cytomegalovirus viremia clearance at week 8 (primary endpoint) and cytomegalovirus viremia clearance plus symptom control at the end of week 8 maintained through week 16 (key secondary endpoint) were assessed. Graft outcomes and treatment-emergent adverse events were analyzed. RESULTS: A higher proportion of maribavir-treated patients achieved the primary endpoint than with IAT across transplant organ types, including kidney (maribavir: 59.5%, IAT: 34.4%), lung (47.5%, 13.6%), and heart (42.9%, 11.1%). Similar proportions of patients achieved the key secondary endpoint in both arms (13.4% versus 11.6%; adjusted difference: 2.4%; 95% CI: -7.05, 11.83%; p=0.620). Rates of treatment-emergent adverse events were: maribavir (96.5%), IAT (88.4%). Maribavir (3.5%)had fewer treatment discontinuations due to treatment-emergent adverse events than IAT (23.2%). There were no graft losses; patients in both arms experienced acute rejection (maribavir: 9 [6.3%]; IAT: 4 [5.8%]). Treatment-emergent maribavir mutations occurred in 28.2% of patients; 19/33 patients achieved viremia clearance with subsequent alternative treatment. CONCLUSIONS: Consistent with findings in the overall SOLSTICE population, this subgroup analysis of SOT recipients demonstrated greater effectiveness of maribavir for cytomegalovirus viremia clearance and fewer discontinuations due to treatment-emergent adverse events than IAT. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov; NCT02931539 J Heart Lung Transplant 2025;44:986-994 (c) 2025 The Authors. Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).

Background: Infectious complications remain an important cause of morbidity/mortality following SOT. Brincidofovir (BCV), a nucleotide analog active in vitro against all major human pathogenic dsDNA viruses, is in Phase 3 development for CMV prevention in HCT. Over 400 patients (pts) have received BCV for serious or life-threatening infections with dsDNA viruses under compassionate use (Study CMX001-350, clinicaltrials.gov ID: NCT01143181 or under emergency INDs).

Background: Specific risk factors for C. difficle infections (CDI) have not been characterized in pediatric small bowel transplantation (SBT). Methods: This 1:3 matched case-control study included 12 CDI patients (cases) and 36 patients who did not develop CDI (controls) during the first year post-SBT, matched based on age, date of transplant, and transplant type. Patients characteristics were compared with Wilcoxon rank-sum, chi-square or Fisher's exact tests. Univariate regression analysis was performed to identify risk factors for CDI. Results: The demographics of the patients are presented in the Table 1Table: No Caption available.There was no difference between cases and controls in the induction therapy and maintenance immunosuppression. On univariate analysis, only CMV D-R+ sero-status (OR=9.0, 95% CI:1.2-67.4, p=0.03), PPI use (OR=4.2, 95% CI:1.1-16.6, p=0.04) and presence of jejunostomy (OR=6.0, 95% CI:1.5-24.3, p=0.012) remained risk factors for CDI. Conclusion: The study demonstrates that use of PPI, CMV D-/R+ sero-status and presence of jejunostomy are risk factors for CDI in pediatric SBT. This new information could increase awareness regarding CDI and optimize outcomes in this vulnerable population.

Background: The incidence C. difficile infections (CDI) in children have increased over the past decade. However, the changes in incidence in pediatric small bowel transplant (SBT) recipients are poorly defined. Methods: Summary statistics were presented for demographics and outcomes. We performed descriptive analysis to determine the incidence and Kaplan-Meier curve analysis to determine the timing of events after transplantation. Results: Ninty-three pediatric patients with mean age 2.7 years (±3.2) underwent SBT. Allograft types were: isolated SBT (22.8%), liver-small bowel-pancreas transplant (77.2%). The induction therapy was: basiliximab (90%), thymoglobulin (4.4%), basiliximab+thymoglobulin (3.3%); maintenance immunosuppression regimen: tacrolimus (100%), sirolimus (11.1%), cyclosporine (3.3%), steroids (100%).Thirteen patients developed CDI (incidence 14.4%) during the first year after transplantation, at a median time of 204 days (range 17-354 days) post-transplantation. The incidence by year is presented in Figure 1.Figure: No Caption available.Treatment consisted of metronidazole (71%), oral vancomycin (18%) and combination metronidazole-vancomycin (12%). No patients required colectomy. Three (18%) patients had recurrent disease. Conclusion: CDI is a late (> 6 months) post-transplant complication in pediatric SBT recipients. We detected an increase in the incidence of CDI.

Background: Brincidofovir (CMX001, BCV) is an oral nucleotide analog, in Phase 3 development for CMV prevention, with broad-spectrum in vitro antiviral activity against double stranded DNA (dsDNA) viruses, including cytomegalovirus (CMV), adenovirus, BK virus and herpes simplex viruses. BCV was administered in patients with refractory or resistant dsDNA viral infections, including CMV infections, in an expanded access protocol (Study 350). Methods: Renal transplant patients with refractory CMV infection who received BCV >/= one week were evaluated for safety and efficacy. Five patients (4 renal and 1 renal/pancreas transplant recipients) with resistant or refractory CMV infection were given BCV 100-200 mg twice weekly. Results: Five adult patients (44-56 years of age) were treated with BCV for CMV viremia (3/5 viremia only) and CMV syndrome (2/5). Three patients received 2 or more renal transplants prior to BCV treatment. All patients received immunosuppressants (IS) and 1 had an increase in IS therapy during BCV treatment. All received previous treatments for CMV (Foscarnet 2/5, GCV 1/5, vGCV 3/5). Initial BCV doses ranged from 100 to 200 mg twice weekly with a median duration of treatment of 91 days (10-171). At the end of treatment, 3 patients had a complete virologic response (