Dima Kabbani

Background: Solid organ transplant (SOT) recipients are at increased risk for severe respiratory syncytial virus (RSV) disease due to chronic immunosuppression. Methods: In this ongoing, open-label, phase 3 trial, adults ≥18 years with a history of liver, kidney, or lung transplant received 2 doses of mRNA-1345 RSV vaccine (50 µg) 56 days apart. Primary endpoints were tolerability, safety, and RSV-A/RSV-B neutralizing antibody (nAb) responses on Day 85; secondary endpoints included immunogenicity on Days 29 and 181. Cell-mediated immunity was an exploratory endpoint assessed in a subset of participants. Results: 146/150 participants (median: age, 57 years; time since transplant, 4.7 years) received both doses. Reactogenicity was mild to moderate and transient. No vaccine-related discontinuations, deaths, adverse events of special interest (AESIs), or events of transplant rejection were reported within 28 days after any dose. One dose was immunogenic across all SOT types, with 4.9- and 3.4-fold increases in RSV-A/RSV-B nAb GMTs by Day 29, respectively. A second dose resulted in modest additional increases over baseline (RSV-A, 7.1-fold; RSV-B, 5.2-fold). Added benefit of the second dose was more apparent in participants with kidney and lung transplant, <2 years post-transplant, and on mycophenolate. Responses remained above baseline through Day 181. Polyfunctional CD4⁺ T-cell responses were robust and sustained; CD8⁺ responses were also observed. Conclusions: mRNA-1345 was well tolerated and immunogenic in SOT recipients. A single dose induced nAb responses across subgroups, with potential additional benefit from a second dose in specific groups. Durable antibody and cellular responses support mRNA-1345 as a preventive strategy for RSV in this vulnerable population. Clinical Trials Registration: NCT06067230.

Background High-risk populations, including transplant recipients, are at increased risk of severe Coronavirus disease 2019 (COVID-19) outcomes. Certain treatments and pre-exposure prophylaxis (PrEP) have been approved to reduce the risk of severe illness. However, data on the cost effectiveness of currently approved COVID-19 therapeutics and preventative treatments are limited for those at high-risk of severe disease. Objective The aim of this study was to systematically review the cost effectiveness of COVID-19 treatments and PrEP in high-risk, immunocompromised, and transplant populations. Methods Electronic databases were searched from inception to September 2025 for studies comparing costs and effectiveness of monoclonal antibodies PrEP or COVID-19 therapeutics in high-risk, immunocompromised or transplant populations. Two reviewers independently screened studies, extracted data, and critically appraised them using the Joanna Briggs Institute checklist for economic evaluations. Cost data are presented in 2025 US dollars. Results Of 8905 studies identified, 60 met inclusion criteria, with seven focused on or including transplant populations. Most studies were cost-utility analyses published between 2020 and 2025. Nirmatrelvir-ritonavir, tixagevimab-cilgavimab, casirivimab-imdevimab, sotrovimab, remdesivir, molnupiravir, and fluvoxamine were compared with no prophylaxis or standard of care. Among transplant populations, the incremental cost-effectiveness ratio (ICER) for tixagevimab-cilgavimab PrEP following vaccination was US$76,024 per quality-adjusted life year (QALY), while ICERs for COVID-19 therapeutics ranged from US$440 to US$126,676 per QALY. Conclusion Cost effectiveness varied widely across studies due to differences in variant periods, population risk profiles, model assumptions, and healthcare systems. Future research should integrate variant-specific effectiveness, real-world vaccine responsiveness, long-term COVID-19 outcomes, and adverse events to better inform resource allocation for transplant and other high-risk populations.

Background: This is the first reported case of empyema due to Mycoplasma hominis in a pediatric transplant recipient. Methods: A 16‐year‐old Indigenous Canadian boy developed acute respiratory distress 29 days post‐bilateral lung transplantation for chronic lung disease and pulmonary hypertension secondary to extreme prematurity and an atrial septal defect. Pre‐transplant donor bronchial cultures grew Candida albicans and methicillin‐sensitive Staphylococcus aureus , so he received 14 days of cefazolin. Post‐transplant prophylaxis included azithromycin, voriconazole, micafungin, TMP‐SMX, and valacyclovir. Immunosuppression included anti‐thymocyte globulin induction, followed by tacrolimus, mycophenolate mofetil, and prednisone. The patient developed a large right pleural effusion over the course of 24 h requiring intensive care and high‐flow supplemental oxygen. Pleural thoracentesis revealed a neutrophil‐predominant exudative empyema. Routine cultures were negative; M. hominis was detected by PCR and specialized media. The patient completed 28 days of clindamycin and doxycycline and made an uneventful recovery. Results: M. hominis and Ureaplasma species are donor‐derived pathogens that can cause significant morbidity, including sternal wound infection, mediastinitis, pericarditis, and empyema. Post‐lung transplant M. hominis infections occur in 2%–5% of cases. Diagnostic challenges, low clinical suspicion, and rising resistance contribute to poor outcomes and inappropriate antibiotic use. Although this patient's ammonia level was normal, hyperammonemia syndrome also remains a rare but serious complication of Ureaplasma urealyticum and M. hominis infections. Conclusion: Early screening, PCR testing, and prompt combination empiric therapy are crucial for improving outcomes in M. hominis infections.

Objective: This study aimed to compare appropriateness of restricted antimicrobial prescriptions, as assessed by antimicrobial stewardship program (ASP) prospective audit and feedback (PAF), between those ordered by medical trainees versus staff. Secondary objectives were to determine whether certain timing factors and other independent variables impacted prescription appropriateness. Design: Single center, retrospective cohort study. Setting: The University of Alberta Hospital a 700-bed tertiary care hospital in Edmonton, Canada. Participants: Prescriptions of six health-authority restricted antibiotics subject to ASP PAF between 2018 and 2023. Cases were excluded if prescriber role or prescription dates or times were unavailable. Methods: Data from a local ASP quality improvement database was extracted. Multiple logistic regression analysis was completed with adjusted odds ratios (aOR) reported. Results: A total of 3,687 restricted antibiotic prescriptions subjected to PAF were included in this study, of which 1,163 (31.5%) were assessed as not appropriately prescribed. Prescriptions written by medical trainees did not have higher odds of appropriateness compared to staff (aOR 1.09 [95% CI 0.94–1.28], P = .25). Weekend prescriptions had a reduced odds of being appropriate (aOR 0.71 [0.60–0.84], P < .0001). Through the course of the Coronavirus Disease 2019 (COVID-19) pandemic, appropriateness improved from 56.2% (prepandemic), 71.5% (peri-pandemic) to 76.9% (postpandemic). Conclusions: No differences were noted in restricted antibiotic prescription appropriateness between medical trainees and staff. Weekend prescriptions were less likely to be appropriate. Improved appropriateness over time may be multifactorial, including implementation of ASP preceding the pandemic. Further studies examining timing factors associated with appropriateness are needed.

Measles exposures have historically been rare since the introduction of routine vaccination programs, resulting in a lack of attention from cancer patients, hematopoietic stem cell transplant (HCT) recipients, patients receiving cellular therapy (CT) and their healthcare providers. It is essential to acknowledge the importance of vigilance in these situations. Measles herd immunity has declined significantly in North America due to rising vaccine hesitancy, resulting in outbreaks. Measles can result in severe outcomes, and its reemergence has raised alarm among patients and healthcare professionals caring for HCT/CT recipients. Patients with severe immunocompromising conditions cannot receive live-attenuated vaccines, such as the measles vaccine. The lack of data on measles prevention in this vulnerable group presents significant clinical challenges. In response, Cell Therapy Transplant Canada (CTTC) Infectious Diseases Working Committee has developed a set of frequently asked questions to provide expert guidance to HCT and CT recipients, acknowledging the limited evidence base.

Background: Primary graft dysfunction (PGD) is a form of immediate post‐transplant acute lung injury associated with increased risk of mortality, and it is possible that respiratory viruses (RVs) at the time of transplant may augment this. Methods: We retrospectively studied all adult lung transplant recipients transplanted in our program from 2017 to 2020, with a primary outcome of grade 3 PGD (PGD3), defined as edema on chest X‐ray and arterial oxygen/fraction of inspired oxygen ratio 30 (odds ratio 0.93 [95% confidence interval 0.38–2.49; p = 0.8845]). Conclusions: Perioperative RVs were not associated with a difference in the risk of PGD3 in our cohort. This may have implications for donor and recipient selection and preoperative evaluation. image

Background: Mycobacterium abscessus complex is known to cause life‐threatening disease in lung transplantation (LT) recipients (LTRs). Therefore, many centers consider the presence of M. abscessus as a relative contraindication to LT.Methods: We conducted a multicenter retrospective cohort study including all 4 LT centers in Canada. All LTRs transplanted in 2006–2016 with at least one respiratory sample positive for M. abscessus prior or posttransplantation were included. Pulmonary disease was defined using the American Thoracic Society criteria. Minimal follow‐up duration was 5 years after transplantation.Results: Among 2181 LTRs across Canada, 14 had M. abscessus disease after LT (incidence rate 1.1/1000 transplant‐years) and 6 had pulmonary colonization (incidence rate 0.5/1000 transplant‐years). Fifteen patients had M. abscessus cultured before LT. Among those with pretransplant M. abscessus, 53% (8/15) developed M. abscessus infection posttransplant (6 disease, 2 colonization). Posttransplant disease was less frequent among those with microbiologic eradication before transplant (0% vs. 85.7%, p = 0.001). LTRs with pretransplant M. abscessus had comparable survival to those without M. abscessus (log rank p = 0.37). Among patients with pretransplant infection, mortality was higher in those who did not achieve microbiological eradication before transplantation (57.1% vs. 0%, p = 0.03) and those who developed disease after transplantation (66.7% vs. 0%, p = 0.01).Conclusions: M. abscessus is an uncommon cause of infection among LTRs. Survival among those with pretransplant M. abscessus infection was similar to that observed in noninfected LTRs. However, lack of eradication before transplantation was associated with higher posttransplant disease and mortality.

Background: Cytomegalovirus (CMV) mismatched, donor IgG‐positive/recipient IgG‐negative, solid organ transplant recipients (SOTRs) are at high risk of CMV invasive disease. Post‐prophylaxis disease is an issue in this population. Some programs employ surveillance after prophylaxis (SAP) to limit the incidence of post‐prophylaxis disease. Methods: This was a single‐center retrospective cohort study that included all CMV mismatched SOTRs from 2003 to 2017. Patients underwent SAP with weekly CMV plasma viral load for 12 weeks. The subjects were classified into three post‐prophylaxis DNAemia patterns: no DNAemia, one episode of DNAemia, and multiple episodes of DNAemia. We calculated the cumulative incidence of each DNAemia pattern. We also determined 5‐year mortality based on DNAemia pattern stratified by organ transplant type. Results: Post‐prophylaxis recurrent DNAemia occurred in 63% of lung recipients and 32% of non‐lung recipients ( p = .003). Tissue invasive CMV disease was diagnosed in 3% of the population and CMV syndrome was diagnosed in 33%. Recurrent DNAemia was not associated with 5‐year mortality. Conclusion: In this cohort, undergoing SAP tissue invasive disease was uncommon and CMV DNAemia recurrence did not have an impact on long‐term mortality. image