Rabbit Antithymocyte Globulin for Treatment of Corticosteroid Refractory Acute Cellular Rejection After Lung Transplantation.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) remains a major cause of death after the first year posttransplant, with acute cellular rejection (ACR) being a major risk factor for CLAD. We evaluated the use of rabbit antithymocyte globulin (rATG) for corticosteroid refractory ACR in lung transplant recipients. METHODS: We retrospectively identified 112 adult lung transplant recipients who received rATG for refractory ACR after lung transplantation. The primary endpoint was the incidence of ACR on follow-up transbronchial biopsy. Secondary endpoints included freedom from ACR within 1 y post-rATG, CLAD progression at 1 y post-rATG, and all-cause mortality at 1 y post-rATG. RESULTS: A complete resolution of ACR was observed in 60.2% of patients, an improvement but not complete resolution in 22.1%, and no response on follow-up biopsy in 17.8%. Mean A grade 1 y post-rATG was 0.51 in complete responders, 1.01 in partial responders, and 2.19 in nonresponders ( P < 0.001). Complete responders had significantly less new or worsening CLAD at 1 y than partial responders (17% versus 40%; P = 0.02). All-cause mortality rate was 14.9% in complete responders, 40% in partial responders, and 30% in nonresponders ( P < 0.01). CONCLUSIONS: rATG appears to be an effective treatment of refractory ACR in lung transplant recipients. Failure to respond to rATG carries an increased risk of early CLAD and death.

Phage therapy in a lung transplant recipient with cystic fibrosis infected with multidrug-resistant Burkholderia multivorans.

BACKGROUND: There is increased interest in bacteriophage (phage) therapy to treat infections caused by antibiotic-resistant bacteria. A lung transplant recipient with cystic fibrosis and Burkholderia multivorans infection was treated with inhaled phage therapy for 7 days before she died. METHODS: Phages were given via nebulization through the mechanical ventilation circuit. Remnant respiratory specimens and serum were collected. We quantified phage and bacterial deoxyribonucleic acid (DNA) using quantitative polymerase chain reaction, and tested phage neutralization in the presence of patient serum. We performed whole genome sequencing and antibiotic and phage susceptibility testing on 15 B. multivorans isolates. Finally, we extracted lipopolysaccharide (LPS) from two isolates and visualized their LPS using gel electrophoresis. RESULTS: Phage therapy was temporally followed by a temporary improvement in leukocytosis and hemodynamics, followed by worsening leukocytosis on day 5, deterioration on day 7, and death on day 8. We detected phage DNA in respiratory samples after 6 days of nebulized phage therapy. Bacterial DNA in respiratory samples decreased over time, and no serum neutralization was detected. Isolates collected between 2001 and 2020 were closely related but differed in their antibiotic and phage susceptibility profiles. Early isolates were not susceptible to the phage used for therapy, while later isolates, including two isolates collected during phage therapy, were susceptible. Susceptibility to the phage used for therapy was correlated with differences in O-antigen profiles of an early versus a late isolate. CONCLUSIONS: This case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.

Induction Strategies in Lung Transplantation: Alemtuzumab vs. Basiliximab a Single-Center Experience.

Background: Induction therapy is used in about 80% of lung transplant centers and is increasing globally. Currently, there are no standards or guidelines for the use of induction therapy. At our institution, we have two induction strategies, basiliximab, and alemtuzumab. The goal of this manuscript is to share our experience and practice since this is an area of controversy. Methods: We retrospectively reviewed 807 lung transplants performed at our institution between 2011 and 2020. Indications for the use of the basiliximab protocol were as follows: patients over the age of 70 years, history of cancer, hepatitis C virus or human immunodeficiency virus infection history, and cytomegalovirus or Epstein-Barr virus (donor positive/ recipient negative). In the absence of these clinical factors, the alemtuzumab protocol was used. Results: 453 patients underwent alemtuzumab induction and 354 patients underwent basiliximab. There were significant differences in delayed chest closure (24.7% alemtuzumab vs 31.4% basiliximab, p = 0.037), grade 3 primary graft dysfunction observed within 72 hours (19.9% alemtuzumab vs 29.9% basiliximab, p = 0.002), postoperative hepatic dysfunction (8.8% alemtuzumab vs 14.7% basiliximab, p = 0.009), acute cellular rejection in first year (39.1% alemtuzumab vs 53.4% basiliximab, p < 0.001). The overall survival rate of the patients with alemtuzumab induction was significantly higher than those of the patients with basiliximab induction (5 years survival rate: 64.1% alemtuzumab vs 52.3%, basiliximab, p < 0.001). Multivariate Cox regression analysis confirmed lower 5-year survival for basiliximab induction (HR = 1.41, p = 0.02), recipient cytomegalovirus positive (HR = 1.49, p = 0.01), postoperative hepatic dysfunction (HR = 2.20, p < 0.001), and acute kidney injury requiring renal replacement therapy (HR = 2.27, p < 0.001). Conclusions: In this single center retrospective review, there was a significant difference in survival rates between induction strategies. This outcome may be attributable to differences in recipient characteristics between the groups. However, the Alemtuzumab group experienced less episodes of acute cellular rejection within the first year.