Citations

Background. Nocardia is an environmental pathogen with a predilection for causing opportunistic infections in immunocompromised patients, including solid organ transplant (SOT) recipients. Although risk factors have been identified for developing nocardiosis in this population, little is known regarding clinical factors resulting in poor outcomes. We evaluated a cohort of SOT recipients with nocardiosis for associations with 12-month mortality. Methods. We performed a multicenter retrospective cohort study of adult SOT recipients diagnosed with culture-confirmed nocardiosis from 2000 to 2020. Patients were followed for 12 months after diagnosis, unless abbreviated by mortality. Multivariable Cox regression was performed to analyze associations with 12-month mortality. A subgroup analysis of patients with disseminated nocardiosis was performed to analyze treatment variables. Results. A total of 125 SOT recipients met inclusion criteria; 12-month mortality was 16.8%. Liver transplantation (hazard ratio [HR] 3.52; 95% confidence interval [CI] 1.27-9.76) and time from symptom onset to presentation (HR 0.92/d; 95% CI 0.86-0.99) were independently associated with 12-month mortality, whereas disseminated infection was not (HR 1.23; 95% CI 0.49-3.13). No treatment-specific factors were significantly associated with mortality in 33 patients with disseminated nocardiosis, although survivors had a higher rate of linezolid use. Conclusions. This study identified 2 independent associations with 12-month mortality, representing demographics and infection severity. Disseminated infection was not independently associated with poor outcomes, and specific sites of infection may be more important than dissemination itself. No treatment-specific factors were associated with mortality, though this analysis was likely underpowered. Further study of treatment strategies based on specific Nocardia syndromes is warranted.

Abstract Background Solid organ transplant recipients (SOTRs) are at high‐risk for severe infection from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Anti‐spike monoclonal antibodies are currently utilized under emergency use authorization to prevent hospitalization in high‐risk individuals with coronavirus disease 2019 (COVID‐19), including SOTRs. However, clinical data for bebtelovimab, the sole currently available anti‐spike monoclonal antibody for COVID‐19, is limited. Methods We conducted a retrospective cohort study of adult SOTRs diagnosed with mild‐to‐moderate COVID‐19 from January 2022 through May 2022 who received either bebtelovimab or sotrovimab. The primary outcome was COVID‐19‐related hospitalization within 30 days of COVID‐19 diagnosis. Data were analyzed with Fisher's exact test. Results Among 361 SOTRs, 92 (25.5%) received bebtelovimab and 269 (74.5%) received sotrovimab. The most common organ transplant was a kidney (42.4%). SOTRs who received bebtelovimab had a higher proportion who had received a booster SARS‐CoV‐2 vaccine dose and had received their last vaccination dose more recently. Eleven (3.0%) SOTRs were hospitalized, and rates of hospitalization were similar between monoclonal antibody groups (3.3% versus 3.0%; p > .99). Three patients required admission to an intensive care unit, all of who received sotrovimab. Four (1.1%) patients died within 30 days of COVID‐19 diagnosis, two from each group. Conclusions SOTRs with mild‐to‐moderate COVID‐19 who received bebtelovimab had similar rates of COVID‐19‐related hospitalization as those who received sotrovimab. While differences in vaccination rates and viral subvariants could act as confounders, bebtelovimab appears to be of similar effectiveness as sotrovimab. image

AbstractGraft‐versus‐hostdisease (GVHD) following liver transplantation (LT) is rare but can lead tosignificant mortality. The leading cause of death following GVHD diagnosis isinfectious complications. However, there is a lack of clear descriptions concerning infection and antimicrobial management patterns. Our study aims toprovide the focused details of all infectious complications of acute GVHDfollowing LT. We retrospectively reviewed all adult LT recipients with acute GVHD at Mayo Clinic's Transplant Centers from January 1, 2010, to December 31, 2021. Detailed characteristics of infection in each case were described. Among 4,585 LTs performed during this period, 12 (0.3%) patients developed acuteGVHD. The median time from transplantation to GVHD diagnosis was 49.0 days [IQR 31.5–99.0]. Ten (83.3%) patients developed severe infections leading tomortality. The most common cause of infection was nosocomial bacteremia fromenteric bacteria such as vancomycin‐resistant enterococci and gram‐negative bacilli. Other infections included breakthrough invasive fungal infections,cytomegalovirus (CMV) reactivation, and Clostridioides difficile colitis. Antimicrobial prophylaxis strategies in most cases were based on the degree of neutropenia—these include levofloxacin for bacterial prophylaxis, nebulized pentamidine for Pneumocystis jiroveci pneumonia prophylaxis, posaconazole for invasive fungal prophylaxis, and valganciclovir based on CMVstatus. All GVHD patients with severe infections succumbed to thesecomplications. Ourstudy reiterates that despite prophylaxis, infectious complications in GVHDfollowing LT are common and lead to exceptionally high mortality. Individualizedantimicrobial treatment, prophylaxis and monitoring strategies remain a criticalcomponent of GVHD management. Further study to optimize these practices isrequired. image

AbstractBackgroundCryptococcus spp. infection involving the central nervous system (CNS) is associated with poor outcomes. Current guidelines recommend repeating a cerebrospinal fluid (CSF) fungal culture after 2 weeks of treatment to evaluate for clearance. However, this practice has not clearly been associated with outcomes.ObjectivesWe sought to assess the relationship between CSF fungal clearance at 2 weeks and 12‐month mortality in patients with CNS cryptococcosis.MethodsThis is a retrospective cohort study from 2011 to 2020 of patients with CNS cryptococcosis. Factors associated with 12‐month mortality were assessed with Fisher’s exact test for categorical variables and Mann–Whitney test for continuous variables.ResultsAmong 51 patients with CNS cryptococcosis, 42 (82.4%) were initially CSF culture positive. Among 27 patients with follow‐up CSF culture at 2 weeks, 6 (22.2%) had a positive result. Factors associated with a positive CSF culture at 2 weeks were an initial CSF cryptococcal antigen titre ≥1:2560, fungaemia, and an elevated intracranial pressure requiring therapeutic lumbar punctures. The 12‐month mortality rate was 33.3%, and this was significantly associated with baseline fungaemia, extra‐CNS cryptococcal involvement and requirement of intensive care unit level of care. Lack of CSF culture clearance by 2 weeks was not associated with 12‐month mortality.ConclusionsCNS cryptococcosis has a high mortality rate. A markedly elevated CSF cryptococcal antigen, and opening CSF pressure was associated with lack of CSF culture clearance at 2 weeks of treatment. Severe disseminated disease and cryptococcemia were associated with 12‐month mortality.

Abstract Antispike monoclonal antibody treatment of 180 B-cell-depleted patients with mild-to-moderate coronavirus disease 2019 (COVID-19) resulted in good outcomes overall, with only 12.2% progressing to severe disease, 9.4% requiring hospitalization, 0.6% requiring mechanical ventilation, no deaths within 30 days, and 1.8% developing persistent COVID-19. Antispike monoclonal antibodies appear effective in this immunocompromised population.

AbstractBackgroundSolid organ transplant (SOT) recipients are at increased risk for complications from SARS‐CoV‐2 infection. Little is known regarding clinical course and outcomes of breakthrough COVID‐19 in the fully vaccinated SOT population. We sought to describe our cohort of SOT recipients who developed symptomatic breakthrough COVID‐19 after full vaccination.MethodsWe conducted a retrospective review of SOT recipients diagnosed with COVID‐19 at least 14 days after completing SARS‐CoV‐2 vaccination. Patients were analyzed according to those presenting with mild‐to‐moderate and severe COVID‐19, respectively. We described presenting characteristics, COVID‐19 therapy, and analyzed outcomes including emergency department (ED) visits, hospitalization, and intensive care unit (ICU) admission.ResultsThirty‐five patients met inclusion criteria. These had a mean age of 60.8 years and kidney transplant was the most common SOT type. Five patients presented with severe COVID‐19 at diagnosis, all requiring hospitalization without ICU admission. From the 30 patients who presented with mild‐to‐moderate infection, 28 received casirivimab–imdevimab. Four of these 28 (14.3%) had an ED visit, with one requiring hospital admission (3.4%). No patients required ICU admission.ConclusionBreakthrough COVID‐19 may occur in SOT recipients after full vaccination, though they appear to have acceptable outcomes. Anti‐spike monoclonal antibody therapy for eligible SOT patients may have mitigated clinical progression and improved the outcomes. Further study with large cohorts is warranted.

Abstract Background Nocardia more commonly causes infection in immunocompromised individuals, notably with a relapse rate of approximately 5%. Solid organ transplant recipients will often receive post-treatment prophylaxis as the underlying immunosuppression is unable to be completely removed. However, data supporting this practice is sparse. We sought to evaluate recurrence of nocardiosis in solid organ transplant recipients, specifically evaluating the role of post-treatment prophylaxis. Methods We conducted a retrospective cohort study of solid organ transplant (SOT) recipients at our medical center diagnosed with nocardiosis from 2000 through 2020. We included adult SOT recipients who completed their course of Nocardia therapy. Patients were excluded if they had not yet completed therapy, died prior to completing therapy, or there was no post-therapy follow-up. The primary outcome was Nocardia recurrence. Continuous variables were presented as mean or median with interquartile range (IQR). Results 108 patients meeting inclusion criteria were analyzed. 72 (66.7%) were male and median age was 60 years (IQR 52-65). Most common SOT types were kidney (47.2%), heart (17.6%), kidney-pancreas (11.1%), and lung (11.1%). Median time from transplantation to diagnosis of nocardiosis was 396 days (IQR 154-1071). Most common sites of infection were lung (88.0%), skin (16.7%), brain (13.9%), and blood (6.5%). Multi-organ infection was present in 22.2% and 24.1% were on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at diagnosis. Post-treatment prophylaxis was utilized in 55 (50.9%) patients (Table 1). TMP-SMX was the most common prophylaxis (87.3%; Figure 1). Four patients experienced Nocardia recurrence, 2 of which were receiving TMP-SMX prophylaxis at time of relapse (Table 2). These were dosed as double strength tablet daily and weekly, respectively. Median time from treatment completion to relapse was 255.5 days (range 107-871). Figure 1. Post-Treatment Prophylaxis Regimens for Nocardia in 55 Patients Conclusion Nocardia recurrence in solid organ transplant recipients is an uncommon occurrence. Double strength daily and weekly TMP-SMX prophylaxis does not appear to be entirely protective and relapse may be dependent upon other factors such as primary treatment length. Further study into the use of post-treatment prophylaxis is warranted. Disclosures All Authors: No reported disclosures

AbstractBackgroundImmunocompromised individuals are at risk for Nocardia infection, with a recurrence rate of approximately 5%. Solid organ transplant (SOT) recipients often receive secondary prophylaxis due to their requirement of lifelong immunosuppression. However, data supporting this practice is sparse. We sought to evaluate Nocardia recurrence in SOT recipients, specifically evaluating secondary prophylaxis.MethodsWe conducted a retrospective cohort study of SOT recipients diagnosed with nocardiosis from 2000 through 2020. We included adult SOT recipients who completed their course of Nocardia therapy and had at least 6 months of posttherapy follow‐up. The primary outcome was Nocardia recurrence, which included relapse and reinfection.ResultsOne hundred two patients met inclusion criteria. Sixty‐six (64.7%) were male and mean age was 58.6 ± 11.7 years. Most common SOT types were kidney (46.1%), heart (18.6%), kidney‐pancreas (11.8%), and lung (10.8%). Most common sites of infection were lung (85.3%), skin (17.6%), and brain (14.7%). Secondary prophylaxis was utilized in 53 (52.0%) patients. Trimethoprim‐sulfamethoxazole (TMP‐SMX) single‐strength daily was the most common prophylaxis agent and dose. Five patients (4.9%) experienced Nocardia recurrence, three of which were receiving secondary prophylaxis at time of recurrence. Two recurrences were with the same Nocardia species. Factors associated with recurrence were lung transplantation (p = .011), chronic lung disease (p = .032), and treatment ≤120 days (p = .006). Time from treatment completion to recurrence ranged from 107 to 875 days.ConclusionsNocardia recurrence in SOT recipients is an uncommon event. TMP‐SMX secondary prophylaxis is incompletely protective and recurrence may be dependent upon other factors. Further study of secondary prophylaxis is warranted.