Prophylaxis In Lung Transplant Recipients Research Articles

Tixagevimab/Cilgavimab as SARS-CoV-2 Pre-Exposure Prophylaxis in Lung Transplant Recipients during the Omicron Wave: A Real-World Monocentric Experience.

Lung transplant recipients (LTRs) respond poorly to vaccination. SARS-CoV-2 pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab (TIX/CIL) reduces the incidence of infection and the evolution to severe COVID-19. In vitro data show decreased activity against Omicron variants. We evaluated the clinical efficacy and safety of TIX/CIL in LTRs during the Omicron wave. A prospective observational cohort study was conducted at ISMETT in Palermo (Italy). In June 2022, SARS-CoV-2 PrEP with TIX/CIL 150/150 mg was offered to LTRs. LTRs who received TIX/CIL were compared to LTRs who did not. Logistic regression analysis (adjusted for prior COVID-19, SARS-CoV-2 vaccination, age, years from transplant, and rejection) was performed. The objective of this study was to compare the following among the two populations: prevalence of SARS-CoV-2, length of SARS-CoV-2 positivity, and COVID-19 disease severity. Among 110 eligible LTRs, 79 (72%) received TIX/CIL and 31 (28%) did not. SARS-CoV-2 infections occurred in 6% (n = 5) of patients who received TIX/CIL and 29% (n = 9) of patients who did not (p < 0.001). In both groups, infections were mild/asymptomatic, and no one was hospitalized or died. At multivariate analysis, TIX/CIL was associated with a lower risk of infection (aOR 0.22; 95%CI 0.06-0.78; p = 0.02). TIX/CIL was safe and effective in reducing the risk of SARS-CoV-2 in LTRs during the Omicron wave.

Use of letermovir for cytomegalovirus primary prophylaxis in lung transplant recipients.

Cytomegalovirus (CMV) is a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard-of-care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV). Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D-/R-), survived <90 days post-LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0×109/L), severe leukopenia (WBC ≤ 2.0×109/L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte-colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post-PPX CMV infection. 204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non-lymphocyte-depleting induction (96.6%) and moderate-risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post-transplant. Patients on VGC experienced significantly more leukopenia (82.3%vs. 58.6%, p = 0.008), severe leukopenia (57.1%vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9%vs. 51.7%, p = 0.048). Breakthrough (5.7%vs. 3.4%, p = 0.955) and post-PPX (24.6%vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high-risk serostatus showed similar trends, though did not reach statistical significance. In this single-center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post-PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX.

Gram-negative bacterial colonizations before bilateral lung transplant. The impact of ‘targeted’ versus ‘standard’ surgical prophylaxis

BackgroundInfections are one of the most common causes of death after lung transplant (LT). However, the benefit of ‘targeted’ prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear.MethodsAll consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016–2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis (‘standard’ vs. ‘targeted’ on the preoperative bacterial isolation).ResultsOne hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to ‘targeted’ prophylaxis, while 24 (52%) to ‘standard’ prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with ‘standard’ prophylaxis and twelve (75%) with ‘targeted’ therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the ‘standard’ and 11 to the ‘targeted’ prophylaxis (p = 0.027).ConclusionsThe administration of a ‘targeted’ prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections.

Implementation of routine Clostridioides difficile infection (CDI) primary prophylaxis in lung transplant recipients.

Lung transplant recipients are at an increased risk for Clostridioides difficile infection (CDI), and those who develop CDI post-transplant can have worsened outcomes including graft failure and death. We sought to describe the efficacy and safety of primary CDI prophylaxis with oral vancomycin among 86 adult lung transplant recipients. Overall, we observed a 9.3% (8/86) incidence of CDI among patients receiving prophylaxis, with the majority of infections occurring a median of 25 days after completion of prophylaxis. Furthermore, we observed a 4.7% incidence of VRE infection/colonization. Opportunities exist to optimize the duration of CDI prophylaxis to balance the benefits and risks in lung transplant recipients.

Real-world experience of Quantiferon-CMV directed prophylaxis in lung transplant recipients

The Quantiferon-Cytomegalovirus (QF-CMV) assay was introduced to predict CMV infection and inform prophylaxis duration in our lung transplant recipients (LTR) from 2012. The aims of this retrospective cohort study were to review our QF-CMV experience, understand factors associated with positive results and further explore its predictive utility. LTR with QF-CMV testing performed at 5 months post-transplant were included. Patients receiving QF-directed prophylaxis (5 or 11 months) were compared to those receiving our prior standard of care (5 months). Outcomes were CMV infection >1,000 IU/mL in blood and/or bronchoalveolar lavage fluid. Factors associated with positive QF-CMV results were identified. Patients were compared based on serostatus, QF-CMV results and prophylaxis duration. Our cohort included 263 LTR (59 D+/R-, 204 R+). QF-directed prophylaxis was used in 195 of 263 (74%) and was associated with reduced CMV infection (84/195, 43% vs 41/68, 60%, p < .001). Patients receiving extended prophylaxis experienced less CMV if negative and/or indeterminate (43% vs 70%, p < .01) or positive (10% vs 51%, p < .01). Only 5 of 59 (8%) D+/R- patients were QF-CMV positive compared to 155 of 204 (76%) R+ patients (adjusted OR 0.03, 0.01-0.07, p < .001). After controlling for prophylaxis duration, only D+/R- serostatus remained independently associated with CMV infection (adjusted HR 4.90, 95% CI 2.68-9.00, p < .0001). QF-CMV results were strongly correlated with serostatus, with D+/R- patients unlikely to test positive while receiving prophylaxis. Extended prophylaxis was associated with delayed onset, reduced frequency and severity of CMV infection across all subgroups. After accounting for serostatus, the incremental predictive value of QF-CMV in this cohort was limited.

Prophylaxis in Lung Transplant Recipients.

Prophylaxis in Lung Transplant Recipients.

Safety of Inhaled Amphotericin B Lipid Complex as Antifungal Prophylaxis in Lung Transplant Recipients.

Inhaled formulations of amphotericin B are the most widely used antifungal prophylactic agents in lung transplant recipients, yet there are limited data on their safety. We performed a single-center retrospective cohort study of 603 consecutive patients who underwent lung transplantation between 2012 and 2017 and received antifungal prophylaxis with inhaled amphotericin B lipid complex (iABLC) from the day of transplantation until hospital discharge. Of 603 patients, 600 (99.5%) received ≥1 dose of iABLC, and 544 (90.2%) completed the recommended prophylactic course. In total, 4,128 iABLC doses (median, 5; range, 1 to 48 per patient) were administered; 24 patients received >3 months of therapy. Only one (0.2%) patient discontinued therapy due to a drug-attributable adverse event. During the first posttransplant year, 80 (13.3%) patients died (median time to death, 171 days; interquartile range [IQR], 80 to 272 days), and 3,352 (median, 6 per patient) lung biopsies were performed; 414 (68.7%) patients developed biopsy-proven acute cellular rejection. One-year adverse events in our cohort of lung transplant recipients treated with iABLC during transplant hospitalization matched national outcomes for rejection, graft loss, and death. iABLC is a safe and well-tolerated antifungal prophylactic agent in lung transplant recipients.

CMV Pneumonitis After Discontinuation of Prophylaxis Therapy Guided by CMV T-cell Immunity Panel

<h3>Introduction</h3> CMV T-cell immunity panels (TCIP) may reliably qualify T-cell specific CMV immunity, however, utility within lung transplant recipients (LTR) is unclear. We describe one of several CMV pneumonitides occurring in LTR after a positive CMV TCIP. <h3>Case Report</h3> A 61yo bilateral LTR (CMV donor IgG+/recipient IgG-) for COPD was admitted for worsening dyspnea 17mo post-LT. During admission, he experienced persistent leukopenia requiring multiple granulocyte colony-stimulating factor doses, MMF discontinuation, and frequent bronchoscopy for clearance. Respiratory cultures were positive for <i>Aspergillus</i> species only. Despite drug modification, his WBC and ANC ranged 1-4K cells/µL and ∼1K cells/µL, respectively. Durable CMV seroconversion to IgG+ occurred 9.5mo post-LT. No prior CMV viremia occurred and only 2 episodes on bronchoalveolar lavage (BAL) viral shedding ranging 1243-2762 copies/mL, with the second episode occurring 3 months prior to current admission. During hospitalization, a CMV TCIP showed immunity [(reference range >0.20%) CD4+ CMV IFN-ɣ cells = 3.08%; CD8+ CMV IFN-ɣ = 10.64%; CD4+ control = 1.93%; CD8+ control = 8.28%]. Subsequently, valganciclovir (VGCV) was discontinued to reduce further bone marrow suppression. One month after VGCV cessation, routine plasma CMV PCR monitoring resulted 740 copies/mL with BAL 37114 copies/mL. Lung tissue pathology and cytology were not performed, however, given the high BAL viral load and persistent graft dysfunction, CMV pneumonitis was diagnosed and treatment with IV ganciclovir (GCV) was initiated. He received 21d of IV GCV treatment with clinical and virologic improvement, and now remains on lifelong VGCV secondary prophylaxis. <h3>Summary</h3> This case advises caution when interpreting CMV TCIP alone to guide duration of CMV prophylaxis in LTR. Pairing CMV TCIP assay with assessment of patient factors (i.e. age, recipient CMV IgG seroconversion, hypogammaglobulinemia) or need for serial monitoring requires further exploration.

Risk factors of breakthrough aspergillosis in lung transplant recipients receiving itraconazole prophylaxis

IntroductionInvasive Aspergillus infection (IA) in lung transplantation can result in poor outcomes. Itraconazole has been shown to be effective for fungal prophylaxis in lung transplant recipients. However, IA remains a major cause of death after lung transplantation. Therefore, we aimed to clarify the risk factors for IA on itraconazole prophylaxis. MethodsWe examined 120 recipients to uncover their IA epidemiology, clinical characteristics, and outcomes. In addition, a case-control study was performed to identify risk factors of IA. ResultsOf the 120 patients, 12 developed IA under itraconazole prophylaxis. The patient demographics and clinical characteristics were compared among the following two groups: IA group, 12 patients, and control group, 108 patients. Significant differences were observed in age (p = 0.004), history of interstitial pneumonia (p = 0.032), and CMV infection (p < 0.001) between the groups. Before the onset of IA, 92% (11/12) of the patients received itraconazole with trough concentrations above the therapeutic range. IA developed at 272.9 ± 114.1 days after lung transplantation. Of the 12 patients who developed IA, 66.7% (8/12) had early cessation of cytomegalovirus (CMV) prophylaxis due to toxicity of valganciclovir, as follows: leukocytopenia in 4 patients, and renal dysfunction in 4 patients. Of the 8 patients who stopped valganciclovir, 75% (6/8) developed CMV infection subsequently. ConclusionThis study suggests that older age, history of interstitial pneumonia, and CMV infection may be important risk factors for IA on itraconazole prophylaxis. These results may help clinicians optimize prophylactic strategies for IA.

A novel highly bio-available itraconazole formulation (SUBA®-Itraconazole) for anti-fungal prophylaxis in lung transplant recipients.

Antifungal prophylaxis remains a mainstay of lung transplantation, given invasive fungal infection is a common and serious complication after lung transplantation. Choice of systemic agent to prevent invasive fungal infection varies between centers and funding of agents remains challenging. Our center has recently changed from posaconazole to a highly bioavailable formulation of itraconazole (SUBA®-itraconazole) at substantially reduced cost, but safety and toxicity require further assessment. A retrospective study of lung transplant patients receiving systemic antifungal prophylaxis from December 2016 through December 2019 following change from posaconazole to itraconazole as standard practice. 150 patients with lung transplants were managed in this time period, with 88 (59%) receiving at least 1 mold-active triazole during the study period. 48 (58%) of these patients received SUBA®-itraconazole; 68 (82%) received posaconazole and 10 (12%) received voriconazole. The average cost per patient during the study period was significantly lower on SUBA®-itraconazole (mean $1548/patient/6month course) than posaconazole (mean $16921.35/patient/6month course). Target trough concentrations for prophylaxis of itraconazole>0.5mg/L and posaconazole>0.7mg/L were achieved on empiric dosing in 49% and 68% respectively. Overall trough itraconazole (0.50 vs 1.12mg/L, P<.001) and posaconazole (1.37 vs 2.10mg/L P<.001) concentrations were significantly lower in patients with cystic fibrosis. Calcineurin inhibitor dose changes on introduction or cessation were similar for SUBA®-itraconazole and posaconazole. Breakthrough invasive fungal infection and toxicity were rare. SUBA®-itraconazole is well-tolerated, associated with rare breakthrough invasive fungal infection, and lower cost. Prospective studies following general introduction are required to determine long-term safety, tolerability, and efficacy.

The Impact of Antifungal Prophylaxis in Lung Transplant Recipients.

Rationale: Many lung transplant centers prescribe antifungal medications after transplantation to prevent invasive fungal infections (IFIs); however, the effectiveness of antifungal prophylaxis at reducing the risk of all-cause mortality or IFI has not been established.Objectives: We aimed to evaluate the effect of antifungal prophylaxis on all-cause mortality and IFI in lung transplant patients.Methods: Using administrative claims data, we identified adult patients who underwent lung transplantation between January 1, 2005, and December 31, 2018. Propensity score analysis using inverse probability treatment-weighting approach was used to balance the differences in baseline characteristics between those receiving antifungal prophylaxis and those not receiving antifungal prophylaxis. Cox proportional hazards regression was used to compare rates of all-cause mortality and IFI in both groups.Results: We identified 662 lung transplant recipients (LTRs) (387 received prophylaxis and 275 did not). All-cause mortality was significantly lower in those receiving antifungal prophylaxis compared with those not receiving antifungal prophylaxis (event rate per 100 person-years, 8.36 vs. 19.49; hazard ratio, 0.43; 95% confidence interval, 0.26-0.71; P = 0.003). Patients receiving antifungal prophylaxis had a lower rate of IFI compared with those not receiving prophylaxis (event rate per 100 person-years, 14.94 vs. 22.37; hazard ratio, 0.68; 95% confidence interval, 0.44-1.05; P = 0.079), but did not reach statistical significance.Conclusions: In this real-world analysis, antifungal prophylaxis in LTRs was associated with reduced all-cause mortality compared with those not receiving antifungal prophylaxis. Rates of IFI were also lower in those receiving prophylaxis, but this was not statistically significant in our primary analysis.

Antifungal prophylaxis in lung transplant recipients: A systematic review and meta-analysis.

No consensus exists regarding optimal strategy for antifungal prophylaxis following lung transplant. To review data regarding antifungal prophylaxis on the development of fungal infections. We searched MEDLINE, Embase, and Scopus for eligible articles through December 10, 2019. Observational or controlled trials published after January 1, 2001, that pertained to the prevention of fungal infections in adult lung recipients were reviewed independently by two reviewers for inclusion. Of 1702 articles screened, 24 were included. Data were pooled using random effects model to evaluate for the primary outcome of fungal infection. Studies were stratified by prophylactic strategy, medication, and duration (short term<6months and long term≥6months). We found no difference in the odds of fungal infection with universal prophylaxis (49/101) compared to no prophylaxis (36/93) (OR 0.76, CI: 0.03-17.98; I2 =93%) and preemptive therapy (25/195) compared to universal prophylaxis (35/222) (OR 0.91, CI: 0.06-13.80; I2 =93%). The cumulative incidence of fungal infections within 12months was not different with nebulized amphotericin (0.08, CI: 0.04-0.13; I2 =87%) compared to systemic triazoles (0.07, CI: 0.03-0.11; I2 =21%) (P=.65). Likewise, duration of prophylaxis did not impact the incidence of fungal infections (short term: 0.11, CI: 0.05-0.17; I2 =89%; long term: 0.06, CI: 0.03-0.08; I2 =51%; P=.39). We have insufficient evidence to support or exclude a benefit of antifungal prophylaxis.

Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients

Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. A single-center, retrospective study of patients who received isavuconazole (September 2015-February 2018) or voriconazole (September 2013-September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005). Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.

CMV Viremia after Discontinuation of Valganciclovir Prophylaxis in Lung Transplant Recipients

Cytomegalovirus (CMV) remains a significant cause of acute morbidity following lung transplantation, and has been linked to the early onset of chronic allograft rejection. Most lung transplant centers utilize prophylaxis with valganciclovir (VGC) to prevent CMV infection. Long-term VGC therapy can be complicated by adverse side effects that include myelosuppression, leading to early discontinuation. We hypothesize that the risk of CMV infection following withdrawal of VGC will be affected by the D/R serology status. We performed a single center, retrospective study of patients who received a lung transplant between January 1st, 2016 to December 31st, 2018. Patient information included gender; VGC discontinuation due to myelosuppression; time from transplant to VGC discontinuation; and time from VGC discontinuation to first detectable CMV PCR. A total of 112 patients received a lung transplant during the study period (table 1). All patients initiated VGC after transplant. CMV D+/R- patients also received CMV immunoglobulin every 2 weeks for 7 doses. 40 patients (36%) developed CMV viremia, with more than half of these cases occurring in CMV+/- recipients. All but two of these cases occurred following discontinuation of VGC. None of the cases of viremia were associated with end-organ disease. Although recent data suggests that extending VGC prophylaxis up to 18 months in lung transplant patients may offer additional protection, the side effects may limit this practice. Incidence of CMV viremia following discontinuation was highest in D+/R- patients and in patients who discontinued therapy early, but there were no patients with end organ disease. These results support a VGC prophylaxis strategy where duration of therapy is based on D/R serologies coupled with weekly monitoring of CMV PCR for 16 weeks after VGC discontinuation.

1737. Impact of Therapeutic Drug Monitoring (TDM) of Azole Prophylaxis in Lung Transplant Recipients on the Development of Positive Fungal Events

BackgroundThe utility and clinical impact of therapeutic drug monitoring (TDM) of prophylactic azole antifungals in lung transplant recipients is not well described. The objective of this study was to investigate the impact of TDM of azole prophylaxis in lung transplant recipients on the development of positive fungal events.MethodsA retrospective analysis was performed on 47 lung transplant recipients between 2013 and 2018 at Northwestern Memorial Hospital. A positive fungal event was defined as fungal species on BAL culture and/or positive BAL Aspergillus galactomannan (GM) with an index value ≥1.0. Study groups were defined based on attainment of therapeutic trough levels after initiation of oral therapy (therapeutic if posaconazole level ≥0.7 μg/mL or voriconazole ≥1–5.5 μg/mL, subtherapeutic if ≥2 consecutive levels of posaconazole <0.7 μg/mL or voriconazole <1 μg/mL after initial dose increase).ResultsThere were no differences in baseline characteristics (Figure 1). There were a total of 11 fungal events with 3 (12.0%) occurring in the therapeutic cohort and 8 (36.4%) in those subtherapeutic (P = 0.08). In the 5 patients with a positive GM, the mean index was 2.02 ± 0.95. 7/30 (23.3%) of patients on posaconazole had a fungal event, with 2/7 (28.6%) requiring treatment at the time of event. For patients on voriconazole, 4/17 (23.5%) had a fungal event, with 1/4 (25.0%) requiring treatment. Mean time to fungal event was 164.5 ± 8.9 days vs. 135.9 ± 13.7 days in the therapeutic and subtherapeutic group, respectively (P = 0.05).All patients on posaconazole suspension who experienced a fungal event were subtherapeutic (3/3, 100%) compared with the majority of patients on posaconazole delayed release (DR) tablets who achieved therapeutic levels (17/22, 77.3%). Mean posaconazole trough level observed in the patients receiving DR tablet was 2.15 ± 0.95 μg/mL.ConclusionThere was an association between two consecutive subtherapeutic azole prophylaxis levels and positive fungal events indicating a role for TDM in lung transplant recipients. Time to fungal event post-transplant was shorter in subtherapeutic patients. As anticipated, the use of posaconazole suspension resulted in subtherapeutic levels. This study presents an opportunity for further research of the impact of TDM on clinical outcomes to optimize patient care. Disclosures All authors: No reported disclosures.

Antifungal Prophylaxis in Lung Transplant Recipients: A Network Meta-Analysis

Purpose Invasive fungal infections (IFIs), in particular invasive aspergillosis cause significant morbidity and mortality in lung transplant recipients (LTRs). Various antifungal agents are used either for universal or pre-emptive/ targeted prophylaxis. However, as there is a lack of randomized control studies, the best agent for prophylaxis/ pre-emptive treatment remains unknown. Methods We identified studies comparing regimens for antifungal prophylaxis in LTRs. We ran a frequentist network (Figure 1). We checked for inconsistency in the network. We could not reject the null hypothesis that the model was consistent between the direct and indirect estimates. Therefore, the model was run under the consistency assumption. Results Ten observational studies were included, which reported comparisons of liposomal amphotericin B (L-AmB), itraconazole, voriconazole, isavuconazole and no treatment. Amphotericin B was the best agent for reducing the rate of IFI in the network meta-analysis, followed by isavuconazole and voriconazole respectively (Table 1). Conclusion Our network analysis suggests that L-AmB and isavuconazole are the preferred antifungal agents for reducing IFI in LTRs.

Discontinuation of Anti-Fungal Prophylaxis in Lung Transplant Recipients: Why Does It Happen

Purpose The objective of this study was to review the reasons lung transplant recipients discontinue antifungal prophylaxis, as documented by treating physicians. Methods We retrospectively reviewed patients who received a single or double lung transplant at Mayo Clinic Rochester from 2002 to 2010 examining the type of antifungal medication and reasons for discontinuation. Lung transplant recipients at our institution receive triazole therapy, voriconazole or itraconazole, for prevention of invasive fungal infections. Results We identified 102 patients who underwent lung transplant at Mayo Clinic from 2002 to 2010; 11 patients died within 6 months of transplant and were excluded. Of the 91 patients who survived longer than 6 months post lung transplant: 86 received itraconazole, 44 received voriconazole, and 37 received both (Table 1). A significantly higher proportion of patients discontinued voriconazole than itraconazole [31 out of 44 (70.5%) versus 41 out of 86 (47.6%), p=0.01]. Side effects (gastrointestinal intolerance, hepatitis, and fluorosis) were the most common reason for discontinuing voriconazole [20/44 (45.5)] compared to one of the least common reasons itraconazole was discontinued [6/86 (8.4), p Conclusion Itraconazole was discontinued prior to the prophylactic end point significantly less often than voriconazole and appeared to be better tolerated; although, several patients were diagnosed with an invasive fungal infection while on itraconazole prophylaxis.

804. Impact of Azithromycin Prophylaxis in Lung Transplant Recipients on the Risk of Nontuberculous Mycobacterial Infections

BackgroundAzithromycin has been shown to improve FEV1 in lung transplant recipients (LTR) with bronchiolitis obliterans syndrome (BOS). The impact of azithromycin use on the incidence of infections due to Mycobacterium avium complex (MAC) and M. abscessus in LTR is currently unknown.MethodsWe conducted a nested case–control study of a retrospective cohort of adult LTR transplanted between 2007 and 2017. Cases were defined as LTR with nontuberculous mycobacterial (NTM) infections due to MAC and/or M. abscessus. Controls were defined as LTR without NTM infections. NTM infection was defined by presence of pulmonary symptoms and radiographic changes (clinical criteria) in addition to positive cultures from ≥2 sputa or ≥1 bronchial specimens (microbiological criteria) according to the IDSA/ATS criteria. LTR who meet microbiological, but not clinical criteria were considered colonized and not included for analysis. Azithromycin use was defined as ≥90 days for BOS treatment.ResultsAmong 538 LTR, 60% (321/538) were male and 81% (434/538) received double LTs. Indication for LT was idiopathic pulmonary fibrosis (28% [152/538]), chronic obstructive pulmonary disease (23% [121/538]), cystic fibrosis [CF] (13% [68/538]), and other (37% [197/538]). The overall incidence of NTM infections was 4.3% (23/538); of which 65.2% (15/23), 17.4% (4/23), and 17.4% (4/23) were due to MAC, M. abscessus and polymicrobial infections, respectively. Thirty-one percent (165/538) of LTR received azithromycin. LTR who received azithromycin prophylaxis had 0.21 times the odds of developing NTM infections compared with LTR who did not receive azithromycin prophylaxis (OR: 0.21, 95% CI: 0.02 – 0.86, P = 0.02). Age (P = 0.88), type of LT (P = 0.81), pretransplant NTM colonization (P = 0.46), and CF (P = 0.22) were evaluated as possible risk factors, but were not associated with increased risk of developing NTM infections in bivariable analyses. In a multivariable logistic regression model, azithromycin prophylaxis was independently associated with decreased risk of NTM infections after adjusting for CF and pretransplant NTM colonization (aOR: 0.20, 95% CI: 0.05–0.88, P = 0.01).ConclusionAzithromycin use was associated with lower risk of NTM infections due to M. abscessus and MAC in our LTR.Disclosures All authors: No reported disclosures.

2138. Impact of De-escalation of Antibiotic Surgical Prophylaxis in Lung Transplant Recipients

BackgroundGuidelines for perioperative antibiotic prophylaxis in lung transplantation (LT) are limited; since Pseudomonas colonization has been linked to acute graft rejection and development of bronchiolitis obliterans syndrome, some centers utilize an anti-pseudomonal β-lactam as part of the surgical prophylaxis regimen. Internal data from our large academic medical center, a center that does not frequently transplant cystic fibrosis patients, identified low rates of Pseudomonascolonization and infection in LT patients. The surgical prophylaxis regimen was therefore narrowed from vancomycin/piperacillin–tazobactam (VPT) in 2013 to vancomycin/ceftriaxone (VCT). The purpose of this study was to examine the protocol change to on the incidence of Pseudomonas isolation in the post-operative period for lung transplant recipients.MethodsThis was a single-center, retrospective quasi-experimental before-after study of lung transplant recipients from July 2006 to February 2017 comparing patients who received VPT to VCT for surgical prophylaxis. Patients receiving other surgical prophylaxis regimens due to allergy or colonization history were excluded. Donor and recipient culture data from bronchoscopy samples were collected to determine the incidence of Pseudomonas in the 14-day post-transplant period. The secondary outcome was the incidence of post-transplant CDC-defined pneumonia. Statistical analysis was performed using SAS 9.4 (Cary, NC).ResultsOne hundred patients were included in the pre-protocol group (VPT), and 65 in the post-protocol group (VCT). Pseudomonas was recovered in recipient BALs on post-op day 2–14 in 8 (8%) patients in the VPT group compared with 5 (7.7%) patients in the VCT group (P = 1.0). Mean time to Pseudomonas isolation was 8.4 days in the VPT group compared with 5.4 days in the VCT group. Incidence of pneumonia on post-op day 2–14 was 6% in the VPT group vs. 3% in the VCT group (P = 0.48). Surgical site infections were rare in the VCT group with an incidence of 1.5% (1/65).ConclusionIsolation of Pseudomonas was rare in both time periods and an increase was not detected when anti-pseudomonal coverage was removed from the surgical prophylaxis regimen. Safe deescalation of surgical prophylaxis regimens are an important antimicrobial stewardship initiative.Disclosures E. Heil, ALK-Abelló: Grant Investigator, Research grant.

Omega-3 fatty acid supplement skin cancer prophylaxis in lung transplant recipients: A randomized, controlled pilot trial.

Lung transplant recipients (LTRs) are at very high risk of skin cancer. Omega-3 fatty acids (FAs) are anti-inflammatory and immune-modulating and could potentially reduce this risk. We assessed the feasibility of omega-3 FA supplementation to reduce skin cancer among these patients. LTRs aged 18+ years, at least 1 year post-transplant, were recruited from the outpatient clinic of The Prince Charles Hospital, Brisbane. Participants were randomly allocated to 4-times-daily supplements containing either omega-3 FA (3.36 eicosapentaenoic acid [EPA] + docosahexaenoic acid) or placebo (4 g olive oil) for 12 months. Primary outcomes were rates of recruitment, retention, adherence (assessed by plasma omega-3 FA), and safety. Secondary outcomes were incident skin cancers. Among 106 eligible lung transplant recipients, 49 consented to take part (46%) with 25 allocated to omega-3 FA and 24 to placebo supplements. Of these, 22 (88%) and 20 (83%), respectively, completed the trial. After 12 months, median plasma EPA increased substantially in the intervention group (125.0 to 340.0 µmol/L), but not the placebo group (98.0 to 134.5 µmol/L). In the intervention group, 6 patients developed skin cancers compared with 11 in the placebo group, giving an odds ratio (95% confidence interval) of 0.34 (0.09 to 1.32). There were no serious, active intervention-related adverse events. This pilot trial among LTRs showed acceptable recruitment and high retention and adherence. We demonstrated a signal for reduction of new skin cancer cases in those taking omega-3 FA supplements, which supports the notion that a larger, more definitive trial is warranted.