Cystic Fibrosis Lung Transplant Recipients Research Articles

First Successful Pregnancy After Lung Transplantation in Poland—Case Report

Lung transplantation is well-established treatment for patients with advanced lung dysfunction in cystic fibrosis (CF). Pregnancy in CF lung transplant recipients is feasible, although it still remains challenging for even professionals and demands a multidisciplinary approach. We report the case of pregnancy in a 22-year-old woman after lung transplantation (LTx) due to end-stage respiratory failure in the course of CF. The interval from transplant to conception was 2.5 years. In 2019, orthotopic LTx was performed and a 3-drug immunosuppressive scheme was used-tacrolimus, mycophenolate mofetil, and prednisolone. There were no complications in the postoperative course. In April 2022, the patient was confirmed pregnant. All fetotoxic or teratogenic drugs were discontinued. Throughout the whole pregnancy, the patient was regularly monitored in the transplant and obstetrics centers. Due to the vaginal bleeding and irregular contractions at the 33 weeks of pregnancy, the course of steroids was administered. At 38 weeks and 5 days of gestation, she presented premature rupture of membranes. The caesarean section was performed because of breech presentation of the fetus. A live, term daughter was born and according to the screening test she does not have CF. Currently, 12 months after the delivery, the mother's lung function is good. Getting pregnant and having a safe pregnancy after LTx is possible, but it requires a specialized and individual approach. The patient should be well informed about possible complications and risks including graft failure. The patient's attitude and her cooperation with doctors play a major role.

Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients

ObjectivesIn high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to...

Telemonitoring: An opportunity in cystic fibrosis lung transplant recipients

IntroductionTelemedicine has been successfully employed in a wide range of conditions, such as such as chronic lung disease and COVID-19. This study evaluate the role of telemonitoring for the early diagnosis of acute lung allograft dysfunction in cystic fibrosis adults who underwent lung transplant (LuTx). Quality of life and functional level achieved during a 12 months follow up were assessed. MethodsPatients were randomized into two groups; control group received traditional hospital-based follow-up, whereas patients in the intervention group received, on top of standard care, a telemonitoring device, with a pulse oximeter and a spirometer integrated. Telemonitoring data were digitally transmitted to our centre. ResultsSixteen patients were enrolled in each group. No statistically significant difference was found between the two groups in terms of incidence of allograft dysfunction, time from onset of symptoms to diagnosis and time of occurrence from LuTx. Moreover, both groups achieved similar quality of life and functional level. With reference to the telemonitoring group: 1) hospital reported data were consistent with those being remotely registered; 2) adherence to telemonitoring decreased during the follow up; 3) the majority of patients reported a high degree of satisfaction. ConclusionThe COVID19 pandemic highlighted the necessity to investigate alternative practices to treat chronically ill individuals. Telemonitoring is a valuable tool to improve quality care to LuTx recipients.

WS03.03 Clinical outcomes and long-term survival in cystic fibrosis (CF) lung transplant recipients in Belgium

Objectives: Lung transplantation (LTx) is a therapeutic option for cystic fibrosis (CF) patients suffering from end-stage lung disease. Our objective is to report the experience of LTx for CF in Belgium.

Impact of extended sinus surgery on allograft infection, allograft function and overall survival in cystic fibrosis lung transplant recipients.

Studies investigating the impact of sinus surgery for cystic fibrosis (CF) patients performed early after lung transplantation (Ltx) are scarce. Recent studies evaluating frequency of respiratory infections and graft outcomes are not available. To determine whether there is a difference in allograft infection, allograft function and overall survival among CF lung transplant recipients with and without concomitant sinus surgery. Retrospective single-center study. We examined 71 CF patients who underwent Ltx between 2009 and 2019 at our center. Fifty-nine patients had sinus surgery before or/and after transplantation and twelve did not undergo sinus surgery. We assessed the survival, the diagnosis of chronic allograft dysfunction (CLAD) and all elevated (> 5mg/l) c-reactive protein episodes during the observed period. The infectious events of the upper and lower airways were categorized in mild infections (5-15mg/l CRP) and severe infections (> 15mg/l CRP). There was no difference in the long-time overall survival (p = 0.87) and no benefit in the short-term survival at 4 year post-transplant (p = 0.29) in both groups. There was no difference in both groups concerning CLAD diagnosis (p = 0.92). The incidence of severe upper and lower airway infections (CRP > 15mg/l) was significantly decreased in the sinus surgery group (p = 0.015), whereas in mild infections there was a trend to decreased infections in the sinus surgery group (p = 0.056). CF patients undergoing Ltx benefit from extended endoscopicsinus surgery (eESS) in terms of frequency of severe infectious events of the upper and lower airways. There was no difference in overall survival and frequency of CLAD in the two groups.

Post-transplant outcomes among cystic fibrosis patients undergoing lung transplantation colonized by Burkholderia: A single center cohort study

Prior infection with Burkholderia cepacia complex (BCC) has been associated with poorer outcomes after lung transplantation, posing an important dilemma for cystic fibrosis (CF). Although current guidelines consider BCC infection to be a relative contraindication, some centers continue to offer lung transplantation to BCC-infected CF patients. We conducted a retrospective cohort study which included all consecutive CF-LTR between 2000 and 2019 to compare the postoperative survival of BCC-infected CF lung transplant recipients (CF-LTR) to BCC-uninfected patients. We used a Kaplan-Meier analysis to compare survival of BCC-infected to BCC-uninfected CF-LTR and fitted a multivariable Cox model, adjusted for age, sex, BMI and year of transplantation as potential confounders. As an exploratory analysis, Kaplan-Meier curves were also stratified by the presence of BCC and urgency of transplantation. A total of 205 patients were included with a mean age of 30.5 years. Seventeen patients (8%) were infected with BCC prior to LT. Patients were infected with the following species: B. multivorans5, B. vietnamiensis3, combined B. multivorans and B. vietnamiensis3 and others4. None of the patients were infected with B. cenocepacia. Three patients were infected with B. gladioli. One-year survival was 91.7% (188/205) for the entire cohort, 82.4% (14/17) among BCC-infected CF-LTR, and 92.5% (173/188) among BCC uninfected CF-LTR (crude HR=2.19; 95%CI 0.99-4.85; p=0.05). In the multivariable model, presence of BCC was not significantly associated with worse survival (adjusted HR 1.89; 95%CI 0.85-4.24; p=0.12). In the stratified analysis for both presence of BCC and urgency of transplantation, urgency of transplantation among BCC-infected CF-LTR appeared to be associated with poorer outcome (p=0.003 across the 4 subgroups). Our results suggest that non-cenocepacia BCC-infected CF-LTR have comparable survival rate to BCC-uninfected CF-LTR.

Survival difference between high-risk and low-risk CFTR genotypes after lung transplant.

While cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with clinical outcomes in cystic fibrosis patients, it is unknown if genotype impacts lung transplant outcomes. We sought to compare lung transplant survival and time to bronchiolitis obliterans syndrome (BOS) between high-risk, low-risk, and not yet classified CFTR genotypes. We used merged data from the Organ Procurement and Transplantation Network (2005-2017) and United States Cystic Fibrosis Foundation Patient Registry (2005-2016). Cox Proportional Hazards models compared graft failure after lung transplant and time to BOS among high-risk, low-risk, and not yet classified risk CFTR genotype classes. Among 1,830 cystic fibrosis lung transplant recipients, median survival for those with low-risk, high-risk, and not yet classified genotype was 9.83, 6.25, and 5.75 years, respectively. Adjusted Cox models showed recipients with a low-risk genotype had 39% lower risk of death or re-transplant compared to those with high-risk genotype (adjusted HR 0.61, 95% CI=0.40, 0.91). A subset of 1,585 lung transplant recipients were included in the BOS subgroup analysis. Adjusted analyses showed no significant difference of developing BOS among high-risk, low-risk, or not yet classified genotypes. Lung transplant recipients with low-risk CFTR genotype have better survival after transplant compared to recipients with high-risk or not yet classified genotypes. Given these differences, future studies evaluating the mechanism by which CFTR genotype affects post-transplant survival could identify potential targets for intervention.

Macrophage Lysosomal Alkalinization Drives Invasive Aspergillosis in a Mouse Cystic Fibrosis Model of Airway Transplantation.

Cystic fibrosis (CF) lung transplant recipients (LTRs) exhibit a disproportionately high rate of life-threatening invasive aspergillosis (IA). Loss of the cystic fibrosis transmembrane conductance regulator (CFTR-/-) in macrophages (mφs) has been associated with lyosomal alkalinization. We hypothesize that this alkalinization would persist in the iron-laden post-transplant microenvironment increasing the risk of IA. To investigate our hypothesis, we developed a murine CF orthotopic tracheal transplant (OTT) model. Iron levels were detected by immunofluorescence staining and colorimetric assays. Aspergillus fumigatus (Af) invasion was evaluated by Grocott methenamine silver staining. Phagocytosis and killing of Af conidia were examined by flow cytometry and confocal microscopy. pH and lysosomal acidification were measured by LysoSensorTM and LysotrackerTM, respectively. Af was more invasive in the CF airway transplant recipient compared to the WT recipient (p < 0.05). CFTR-/- mφs were alkaline at baseline, a characteristic that was increased with iron-overload. These CFTR-/- mφs were unable to phagocytose and kill Af conidia (p < 0.001). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles acidified lysosomes, restoring the CFTR-/- mφs’ ability to clear conidia. Our results suggest that CFTR-/- mφs’ alkalinization interacts with the iron-loaded transplant microenvironment, decreasing the CF-mφs’ ability to kill Af conidia, which may explain the increased risk of IA. Therapeutic pH modulation after transplantation could decrease the risk of IA.

WS07.06 Geographical distance and survival among adult cystic fibrosis lung transplant recipients in the United States

WS07.06 Geographical distance and survival among adult cystic fibrosis lung transplant recipients in the United States

Use of elexacaftor/tezacaftor/ivacaftor among cystic fibrosis lung transplant recipients

BackgroundCystic fibrosis (CF) lung transplant (LT) recipients may warrant treatment with elexacaftor/tezacaftor/ivacaftor (ETI) to improve extrapulmonary manifestations of CF. Our objectives were to identify reasons for prescribing ETI after LT and evaluate changes in body mass index (BMI), hemoglobin A1c, hemoglobin, and liver enzymes. MethodsThis was an electronic health record-based cohort study, October 2019-September 2020, at 14 CF LT Consortium sites in North America. The study included CF LT recipients prescribed ETI after transplant. Differences in BMI, A1c, and hemoglobin were assessed with paired t-tests. ResultsThere were 94 patients prescribed ETI; indications included sinus disease (68%), GI symptoms (39%), or low BMI (19%). Prescriptions were written by CF physicians (34%), LT physicians (27%), or physicians who practice both CF and LT (39%). Forty patients (42%) stopped ETI at a median of 56 days [IQR 26, 139] after start/prescription date. ETI was not associated with a significant change in BMI (0.2 kg/m2, 95% CI [-0.1, 0.6], p = 0.150), but was associated with decreased A1c (0.4%, 95% CI 0.2, 0.7, p = 0.003), and increased hemoglobin for patients with anemia (0.6 g/dL, 95% CI 0.2, 1.0, p = 0.007). Three people (3%) stopped ETI due to elevated transaminases. ConclusionsETI is rarely prescribed for non-pulmonary indications after LT for CF. Further study is needed to determine the risks and benefits of ETI in the CF lung transplant population given the potential for drug interactions, side effects leading to discontinuation of ETI, and the possible mechanisms for ETI to positively impact long-term post-transplant outcomes.

Effect of Bronchoscopic Interventions on Long-Term Lung Function Among Lung Transplant Recipients due to Cystic Fibrosis: A Single-Center Study

Patients with end-stage lung disease owing to cystic fibrosis may require lung transplant, provided other therapeutic options were exhausted. During the posttransplant period, bronchial anastomoses' healing may sometimes be complicated and require bronchoscopic intervention (BI). The main aim of this study was to assess BI and its effect on long-term lung function among cystic fibrosis lung transplant recipients who have reached 2-year survival. This retrospective study includes 22 patients with cystic fibrosis who underwent primary double lung transplant in a single center between 2018 and 2020 and have checked in for their 2-year follow-up visit. BI is defined as performing endoscopic bronchoplasty through balloon dilatation, cryoprobe, argon plasma, and/or laser treatment. All patients, who did not require BI during the first year, did not need bronchoplasty during the second posttransplant year as well. Results of forced expiratory volume in 1 second as percentage of predicted value and the 6-minute walk distance were similar at 2-year follow-up to those obtained at the end of 1 year for all patients. Significant time effects were observed for forced vital capacity (FVC) (weak effect), FVC as percentage of predicted value (weak effect), and forced expiratory volume in 1 second/FVC (moderate effect). Patients who had never had bronchoscopic intervention owing to airway stenosis, as well as those who did in the first posttransplant year, maintained forced expiratory volume in 1 second as percentage of predicted value at a comparable level at the second posttransplant year follow-up visit. The number of BIs significantly decreased among patients, who were undergoing such procedures during the first posttransplant year.

The Impact of Geographical Distance on Survival in Adult Cystic Fibrosis Lung Transplant Recipients

<h3>Purpose</h3> Cystic fibrosis (CF) remains one of the most common indications for bilateral lung transplantation (LTx) worldwide. Worse outcomes are seen after other organ transplantations than lung, for those living further from transplant centers. To date, the role of distance in lung transplantation outcomes in the United States (US) among people with CF has not been previously studied. The objective of this study was to assess the association of geographical distance with survival among adult CF LTx recipients in the US. <h3>Methods</h3> A retrospective nationwide cohort study of 2,838 adult CF LTx patients from 2005-2019 was conducted using the Scientific Registry of Transplant Recipients. Geographical distance was determined between the recipients' zip code and their transplant center zip code. Patients were stratified into 3 groups based on their distance (<50, 50-150, and >150 miles). The outcome of interest included time from transplantation to death or re-transplantation. All-cause mortality was examined with multivariable Cox proportional hazard regression, and the Kaplan-Meier method was used to model survival after LTx. <h3>Results</h3> Of the 2,838 CF LTx recipients, 1,218 (42.9%) traveled <50 miles; 814 (28.7%) traveled 50-150 miles; and 806 (28.4%) traveled >150 miles. During the study period, 1,170 (41.2%) patients died. There was a significant difference in survival by distance traveled (log-rank p=0.003). Compared to the recipients living within 50 miles of a transplant center, those traveling 50-150 miles (HR=1.20; 95% CI=1.02-1.41) and >150 miles (HR=1.29; 95% CI=1.10-1.52) had a higher risk of death. Younger age, being African American, having lower BMI, and less education had statistically significant negative associations with patient survival. Health insurance and year of transplantation were also found to have statistically significant associations with patient survival. <h3>Conclusion</h3> This study represents the largest cohort evaluating the effect of distance from transplant center on survival in adult CF LTx recipients. Worse survival was seen in patients living further away from their transplant center. Further investigation of the causes that contribute to this observed disparity may aid in improving survival rates of CF LTx recipients, including evaluating the number of clinic visits, transportation issues, cost of travel, or other financial concerns.

Cystic fibrosis lung transplant recipients 10 years of age or younger: Predisposing factors for end-stage disease.

The largest age group among children and adolescents referred for lung transplantation for cystic fibrosis (CF) have been those in the pubertal or postpubertal age range. However, over 100 younger patients with CF have undergone lung transplantation over the last three decades in the United States. We performed a retrospective review of our experience with 18 children with CF who underwent lung transplantation in our center before the age of 11 years and compared them to our older CF lung transplant recipients and our larger CF Center population. The transplant population was demographically distinct from our CF center in terms of ethnicity, country of origin, and insurance status. Other notable findings were a high prevalence of methicillin-resistant Staphylococcus aureus, a high prevalence of CF-related diabetes mellitus, and a high prevalence of consolidated lobar or whole lung disease. Posttransplant outcomes were comparable to those older than 10 years of age in our center until 5 years after transplant after which the younger cohort showed a superior enduring survival. In an era of increasingly effective medications modifying the natural history of CF, identification of risk factors for early severe lung disease in CF remains relevant to permit interventions to prevent or postpone the time of future lung transplantation.

Body Mass Index Recovery after Lung Transplant for Cystic Fibrosis.

Rationale: Many lung transplant recipients with cystic fibrosis (CF) have low preoperative body mass index (BMI); however, post-transplant BMI recovery is not well understood. Objectives: To evaluate BMI recovery (⩾18.5 kg/m2) among CF lung transplant recipients with low preoperative BMI and to investigate the association of survival with BMI recovery. Methods: The United Network for Organ Sharing and CF Foundation patient registries (June 2005-December 2016) were used to identify CF lung transplant recipients. Among recipients surviving ⩾1 year, Cox modeling compared post-transplant 1-year conditional survival between recipients with low (<17 and 17-18.49 kg/m2) versus normal preoperative BMI, stratified by BMI recovery. Results: Of 1,977 CF lung transplant recipients, 272 (14%) and 449 (23%) had a preoperative BMI of <17 and 17-18.49 kg/m2, respectively. For subgroups with a BMI of <17 and 17-18.49 kg/m2, 29% versus 49%, respectively, of those alive at 1 year recovered their BMI. Among recipients with low preoperative BMI, adjusted post-transplant 1-year conditional survival was worse than that in those with preoperative BMI ⩾ 18.5 kg/m2; however, BMI recovery mitigated this. Preoperative BMI < 17 kg/m2 had an adjusted hazard ratio of 1.29 (95% confidence interval [CI], 0.92-1.81) with BMI recovery versus 1.57 (95% CI, 1.09-2.25) without recovery, and preoperative BMI 17-18.49 kg/m2 had an adjusted hazard ratio of 1.28 (95% CI, 1.02-1.61) with BMI recovery versus 1.72 (95% CI, 1.14-2.59) without recovery. Conclusions: Patients with lower preoperative BMI were less likely to achieve BMI recovery within 1 year. However, for those who did, BMI recovery within 1 year after transplant was associated with longer survival.

DUPLICATE: Cystic Fibrosis Foundation Consensus Statements for the Care of Cystic Fibrosis Lung Transplant Recipients

DUPLICATE: Cystic Fibrosis Foundation Consensus Statements for the Care of Cystic Fibrosis Lung Transplant Recipients

Tacrolimus Dosage Adjustments after Posaconazole Discontinuation in Lung Transplant Recipients

Purpose Posaconazole is commonly used in lung transplant recipients (LTRs) as prophylaxis against invasive fungal infections. Due to CYP3A4 drug interactions, tacrolimus (TAC) dose adjustments are required after discontinuing posaconazole. Current data has assessed tacrolimus dose adjustments only with posaconazole initiation. This study's purpose was to assess TAC dose adjustment requirements following posaconazole discontinuation in LTRs. Methods This was a single-center, retrospective review of LTRs between Jan and Dec 2019. The primary outcome was the change in TAC dose‐corrected trough concentration (∆C/D) from pre- to post-posaconazole discontinuation. Secondary outcomes included the time to first therapeutic TAC level post-posaconazole discontinuation and the number of TAC dose changes to achieve the first therapeutic TAC level after stopping posaconazole. Results 19 LTRs were included, the majority of which were Caucasian and CYP3A5 poor metabolizers [Table 1]. The median (IQR) TAC ∆C/D was 3.1 (2.3-4.4). Following posaconazole discontinuation, the median (IQR) time to the first therapeutic TAC level was 19 (14-26) days, and a median (IQR) of 3 (1-4) dose changes were required to achieve the first therapeutic TAC level. There was a trend towards the one CYP3A5 extensive metabolizer having a higher TAC ∆C/D (11.2), compared with poor (3.1) and intermediate metabolizers (3.3), although non-significant (p=0.25). Baseline posaconazole trough level did not impact the TAC ∆C/D (p=0.57). Similarly, baseline TAC trough level did not impact the time to first therapeutic TAC level post-posaconazole discontinuation (p=0.42). Conclusion In this cohort, LTRs required a 3-fold increase in TAC dose to obtain a trough level within goal after posaconazole discontinuation. Further studies are warranted to assess the impact of posaconazole discontinuation on TAC dose adjustments in various CYP3A5 pharmacogenomic phenotypes, cystic fibrosis LTRs, and those receiving TAC extended-release.

Airway epithelial stem cell chimerism in cystic fibrosis lung transplant recipients

BackgroundThe conducting airway epithelium is repaired by tissue specific stem cells (TSC). In response to mild/moderate injury, each TSC repairs a discrete area of the epithelium. In contrast, severe epithelial injury stimulates TSC migration and expands the stem cell's reparative domain. Lung transplantation (LTx) can cause a moderate/severe airway injury and the remodeled airway contains a chimeric mixture of donor and recipient cells. These studies supported the hypothesis, LTx stimulates TSC migration resulting in epithelial chimerism. We tested this hypothesis in cystic fibrosis (CF) LTx patients. MethodsAirway mucosal injury was quantified using bronchoscopic imaging and a novel grading system. Bronchial brushing was used to recover TSC from 10 sites in the recipient and allograft airways. TSC chimerism was quantified by short tandem repeat analysis. TSC self-renewal and differentiation potential were assayed using the clone forming cell frequency and air-liquid-interface methods. Electrophysiology was used to determine if TSC chimerism altered epithelial ion channel activity. ResultsLTx caused a mild to moderate airway mucosal injury. Donor and recipient TSC were identified in 91% of anastomotic sites and 93% of bronchial airways. TSC chimerism did not alter stem cell self-renewal or differentiation potential. The frequency of recipient TSC was proportional to CF Transmembrane Conductance Regulator (CFTR)-dependent ion channel activity and 33% of allograft regions were at risk for abnormal CFTR activity. ConclusionsLTx in CF patients stimulates bidirectional TSC migration across the anastomoses. TSC chimerism may alter ion homeostasis and compromise the host defense capability of the allograft airway epithelium.

Cystic Fibrosis Lung Transplant Recipients Have Suppressed Airway Interferon Responses during Pseudomonas Infection

SummaryLung transplantation can be lifesaving in end-stage cystic fibrosis (CF), but long-term survival is limited by chronic lung allograft dysfunction (CLAD). Persistent upper airway Pseudomonas aeruginosa (PsA) colonization can seed the allograft. While de novo PsA infection is associated with CLAD in non-CF recipients, this association is less clear for CF recipients experiencing PsA recolonization. Here, we evaluate host and pathogen contributions to this phenomenon. In the context of PsA infection, brushings from the airways of CF recipients demonstrate type 1 interferon gene suppression. Airway epithelial cell (AEC) cultures demonstrate similar findings in the absence of pathogens or immune cells, contrasting with the pre-transplant CF AEC phenotype. Type 1 interferon promoters are relatively hypermethylated in CF AECs. CF subjects in this cohort have more mucoid PsA, while non-CF PsA subjects have decreased microbiome α diversity. Peri-transplant protocols may benefit from consideration of this host and microbiome equilibrium.

Lung T-Cell Profile Alterations are Associated with Bronchiolitis Obliterans Syndrome in Cystic Fibrosis Lung Transplant Recipients.

The contribution of T-cells after lung transplant (LTx) remains controversial with no current consensus of their role concerning chronic lung allograft dysfunction. Using flow cytometry to assess T-cell subsets of bronchoalveolar lavage fluid (BALF) in 16 cystic fibrosis (CF) LTx recipients, we identified a decline in CD4+ T-cell frequency and an increase in CD8+ T-cell frequency in patients who developed severe bronchiolitis obliterans syndrome (BOS) (N = 10) when comparing baseline (6months post-LTx) and follow-up (most recent bronchoscopy-clinical or surveillance per protocol). Comparing BOS to No BOS cohorts, significant differences were found in CD4+ T-cell frequency [17.4 (12.5, 28.2) vs 46.6 (44.4, 48.4), p = 0.003] and CD8+ T-cell frequency [65.6 (62.8, 75.3) vs 39.2 (32.2, 43.3), p = 0.014], respectively. The mean difference of the CD4:CD8 ratio was 0.87 units lower (95% CI - 1.44 to - 0.30, p = 0.006) than patients without BOS, while the median difference of the CD4:CD8 ratio was 0.92 units lower (95% CI - 1.83 to - 0.009, p = 0.048). Therefore, our results suggest that T-cell profiles measured through flow cytometry of BALF in the CF LTx population are associated with the development of severe BOS. Further work is needed in larger patient populations to validate our findings and to determine if this is useful for recipients who underwent LTx for other indications.

730. Cefiderocol for the Treatment of Achromobacter xylosoxidans Infections in Two Lung Transplant Patients with Cystic Fibrosis

Background Achromobacter xylosoxidansis a highly resistant Gram-negative bacterium that causes chronic infections in patients with cystic fibrosis (CF). Treatment options for A. xylosoxidans are limited. In the peri-lung transplant setting, the treatment of A. xylosoxidans infections is especially challenging. Cefiderocol is a novel siderophore cephalosporin antibiotic with broad anti-Gram-negative activity, including against A. xylosoxidans. We report here two cases of compassionate use of cefiderocol in CF lung transplant recipients with A. xylosoxidans infection.MethodsCefiderocol was obtained through compassionate use from its manufacturer, with approval from the local Institutional Review Board. In the first case, it was used as salvage treatment, and in the second case as a planned part of the peri-transplant regimen.ResultsA male in his 20s with CF and a trimethoprim-sulfamethoxazole (TMP-SMX) allergy was chronically colonized by A. xylosoxidans, which was sensitive only to piperacillin–tazobactam (PIP-TAZ), and TMP-SMX. After lung transplant, he developed A. xylosoxidansbacteremia, and extended-infusion PIP-TAZ was started. Repeat bronchoscopy grew A. xylosoxidans. Due to lack of improvement, cefiderocol was added to PIP-TAZ with rapid clinical improvement. However, after completing his course, he was readmitted with A. xylosoxidans pneumonia. He was treated with 6 weeks of cefiderocol and imipenem and has been well since with an 8-month follow-up. In the second case, cefiderocol was used as part of the planned peri-transplant regimen for a female with CF in her late teens, with chronic A. xylosoxidans colonization, which was intermediate to PIP-TAZ, and resistant to all other drugs tested. Her native lungs grew 4+ A. xylosoxidans at the time of explant. Post-transplant, she was treated with 5 weeks of meropenem and 6 weeks of cefiderocol. At four-month follow-up, she is doing well. However, she is asymptomatically colonized with A. xylosoxidanspost-transplant. Isolates from both cases were susceptible to cefiderocol (case #1 MIC = 0.12; case #2 pretreatment MIC = 1, post-treatment MIC.ConclusionCefiderocol may be a useful option for lung transplant recipients with A. xylosoxidans infections.DisclosuresAnne Lachiewicz, MD, MPH, MicroGenDx: Consultant; Shionogi: Consultant.