Purpose: It is not known whether outcomes after COVID-19 meaningfully differ for single-lung (SL) and double-lung (DL) transplant recipients. We describe a cohort of SL and DL recipients who were diagnosed with COVID-19.

Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID-19. The objective was to evaluate outcomes among SOTR and describe the drug-drug interaction of NR. This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID-19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre- and post-NR were 7.4 ng/ml (IQR, 6.6-8.6) and 5.2 (IQR, 3.6-8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post-NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re-introduce CNI after the NR course is complete.

Purpose Acute cellular rejection (ACR) affects up to 55% of lung transplant recipients (LTR) within the first year post-transplant. Maintenance immunosuppression regimens include calcineurin inhibitors, antimetabolites, and corticosteroids. Previous studies have shown that early ACR can lead to more severe rejection episodes within the first year post-transplant. The aim of this study is to evaluate the relationship between the time to therapeutic tacrolimus trough concentrations immediately after lung transplant and early clinical ACR post lung transplant. Methods This was a single center, retrospective cohort study of 208 adult LTR transplanted between March 1, 2012 and December 31, 2015 at NewYork-Presbyterian Hospital, Columbia University Irving Medical Center. Recipients were stratified into four groups based on the time to therapeutic tacrolimus concentrations: 0-7, 8-14, 15-29, and ≥30 days post-transplant. Therapeutic tacrolimus trough concentrations were defined as two consecutive levels between 10-15 ng/mL. The primary outcome was the incidence of clinical ACR 6 weeks post-transplant. Clinical ACR included both biopsy proven rejection and treated rejection. Secondary outcomes included biopsy proven ACR 4 and 12 weeks post-transplant and the incidence of acute kidney injury 7, 14, and 30 days post-transplant. Multivariable logistic regression was performed to assess the primary outcome with adjustment for donor age, recipient age, recipient sex, primary graft dysfunction (PGD) within 72 hours post-transplant, and pre-transplant HLA sensitization. Results The incidence of clinical ACR within 6 weeks post-transplant did not differ between groups: 68%, 66%, 71%, and 71% in the 0-7, 8-14, 15-29, and ≥30 days post-transplant groups, respectively (p=0.94). No differences were seen in adjusted and unadjusted analysis. No difference was found in the incidence of AKI within 7 (p=0.25) or 30 (p=0.32) days post-transplant. The incidence of AKI within 14 days was higher in the 15-29 day group (26%), compared to 7%, 14%, 7% in groups 0-7, 8-14, and ≥30 days, respectively (p=0.05). Conclusion There was no difference in the incidence of early clinical ACR among adult LTR who achieved therapeutic tacrolimus trough concentrations 0-7, 8-14, 15-29, or ≥30 days post-transplant.

Cytomegalovirus (CMV) is a major cause of morbidity and mortality in lung transplant recipients (LTR). Studies comparing outcomes between wild type CMV and resistant CMV (rCMV) are lacking. The purpose of this study is to compare outcomes between wild-type CMV and rCMV in LTR. This is an IRB-approved, single-center retrospective study of LTR who were transplanted between 1/10 and 12/14 and developed CMV viremia. Patients who received multi-organ transplants and re-transplants were excluded. Patients were categorized as having rCMV if they had at least one documented CMV panel indicating resistance to ganciclovir, foscarnet, and/or cidofovir. The primary outcome was rate of acute cellular rejection (ACR) after CMV infection. Secondary outcomes included time to ACR, time to resolution of CMV, CMV recurrence, and mortality. 299 patients received a lung transplant during the study period. 98 (33%) developed CMV and 90 were included for analysis. 74 patients (25%) had CMV and 16 (5%) developed rCMV. Baseline characteristics are described in Table 1 and outcomes in Table 2. All LTR in the rCMV group were D+/R-. There were no statistical differences in the rate or time to onset of ACR from infection, duration of viremia, or graft or patient survival. There was a statistically higher rate of recurrence in the rCMV group (80% vs. 28%, p< 0.05). This study did not identify a difference in rate or onset of ACR between in LTR wild-type and resistant CMV, however there was a higher rate of recurrence in the resistant CMV group. Additional study is warranted to characterize the risk factors for and impact of rCMV on LTR.

The dosing of darbepoetin alfa (DA) for treatment of anemia in renal transplant recipients (RTR) is not well described. The recommended starting dose of DA in patients with chronic kidney disease when serum hemoglobin (hgb) levels are <10g/dL, irrespective of dialysis status, is 0.45mcg/kg. The impact of weight-based dosing among obese RTR has not been studied. We hypothesize that obese RTR (BMI ≥30kg/m2) may require higher initial doses of DA for a therapeutic response, compared to non-obese recipients. Methods: Retrospective review of 86 adult RTR who received at least one in-patient dose of darbepoetin alfa between 1/2012 and 6/2013 in the post-transplant period. RTR were stratified into 2 groups: obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2). The primary objective was to evaluate the impact of weight-based dosing and dose response to DA for the treatment of post-transplant anemia. Results: Patients in each group were comparable with respect to age, gender, race, hgb and hematocrit (hct) levels on admission, and initial weight-based DA dosing.Table: No Caption available.Iron stores and the number of patients receiving iron supplementation were comparable, 39.4% of obese and 47.2% of non-obese recipients. Response to the similar weight-based DA dosing, as measured by the change in hgb and hct levels 30 days post dose administration, was significant.Figure: No Caption available.Conclusion: Obese renal transplant recipients appear to have a less significant response to the same weight-based doses of darbepoetin alfa compared to non-obese recipients. Further studies are needed to determine the appropriate dosing strategy for use in obese RTR.

Clostridium difficile (C. difficile) is a bacterial enteric pathogen which causes clinical disease in solid organ transplant (SOT) recipients. This large, single-center study describes the incidence, risk factors, and impact of C. difficile infection (CDI) among SOT recipients. Methods: Retrospective evaluation of adult cardiac (n=5), lung (n=14), liver (n=9), and renal (n=26) SOT recipients transplanted and diagnosed with CDI from 9/2009-12/2012. CDI was diagnosed by C. difficile gene B PCR testing. Lab data, antibiotic therapy, acid-suppressive therapy, abdominal procedures, hospitalizations, and graft and patient outcomes were evaluated. Results: CDI incidence in cardiac, lung, liver, and renal transplant recipients was 1.9%, 7%, 2.7%, and 3.2%, respectively. Median time from transplant to CDI for all recipients was 64(14-253) days, with liver recipients having the shortest time to infection, median 36(15-101) days and lung recipients having a longer time to infection, median 136(29-611) days. Antibiotic exposure within 3 months of CDI occurred in 80%, 79%, 100%, and 58% of cardiac, lung, liver, and renal recipients, respectively; specific agents are outlined.Figure: No Caption available.Median restricted and cumulative antibiotic exposure was longest in lung recipients [restricted: 12(5-20) days; cumulative: 16(11-40) days] and shortest among renal recipients [restricted: 3(0-17) days; cumulative: 3(0-19) days]. Most patients (75%) were hospitalized within the 3 months preceding CDI. Most recipients initially received PO or IV metronidazole monotherapy; 5 patients (cardiac n=1, lung n=3, renal n=1) received initial combination therapy with IV metronidazole and PO vancomycin. 12 patients required escalation of initial therapy. Recipients were followed for a median time of 23(16-31) months post-transplant; 80% of allografts were functional and 83% of patients were alive. One death and 1 graft failure were causally related to CDI. Conclusion: CDI has an overall incidence of 3.4% among SOT recipients. Clinicians caring for SOT recipients should have heightened awareness of CDI, especially in patients receiving frequent and prolonged antibiotic courses, with increased monitoring and aggressive management of CDI.

Darbepoetin alfa (DA) is a frequently used erythropoiesis-stimulating agent to correct anemia after renal transplantation. Initial DA dose for chronic kidney disease (CKD) patients is well established as 0.45mcg/kg; however, dosing and response curves in renal transplant recipients (RTR) are not well described. The purpose of this study is to evaluate DA dosing regimens in RTR with post-transplant anemia. Methods: Retrospective review of 170 adult RTR who received at least one in-patient dose of DA between 1/2012 and 6/2013 in the post-transplant period. RTR were stratified by the DA dosing they received; ≤0.45mcg/kg (n=14) and >0.45mcg/kg (n=156). The primary objective was to compare the impact of these dosing strategies on hemoglobin (Hgb) and hematocrit (Hct) responses at 30-days. Results: With the exception of weight, demographics were similar between groups. As expected, baseline Hgb and Hct levels prior to DA administration were similar. Hgb and Hct increased at 30-days following DA treatment, however there was no difference in mean values between groups despite the difference in DA dosing (Hgb, p=0.198 and Hct, p=0.288). The actual mean dosing difference between groups was 0.5mcg/kg. If patients receiving >0.45mcg/kg were to receive CKD recommended dosing, this would result in a mean cost savings of approximately $364.76 per patient per dose.Table: No Caption available.Conclusion: Patients that received ≤0.45mcg/kg and >0.45mcg/kg for post-transplant anemia had similar follow up Hgb and Hct values at baseline and 30-days following treatment. Higher doses of DA did not demonstrate an additional benefit; therefore, starting doses of 0.45mcg/kg result in decreased cost and utilization of DA.