Bosch, Wendelyn

Abstract Background There is scarce data surrounding the epidemiology of invasive fungal infections (IFI) after pancreas transplantation (PT). Our centers’ PT protocols recommend universal fluconazole prophylaxis for at least 1 month, which is extended to 1 year for recipients who live in Coccidioides endemic areas. The purpose of our study was to evaluate the epidemiology of IFIs after PT while on our antifungal prophylaxis protocol. Methods A retrospective cohort study was performed among adult patients who underwent PT at Mayo Clinic sites in Arizona, Florida, or Minnesota between January 1, 2010 and December 31, 2020. IFI was defined based on EORTC/MSGERC criteria. The primary aim was to describe epidemiology and timing of IFI after PT, particularly in the context of the universal antifungal prophylaxis protocol. Results Among 482 pancreas transplant recipients, 35 developed IFIs (7.3%). All patients received antifungal prophylaxis per protocol for a median duration of 33 days (Figure 1). Median duration from time of transplant to IFI was 16 (IQR 10.5-28.2) days for Candida IFIs versus 529 (IQR 192.5-1195.0) days for non-Candida IFI. 20 IFIs (57.1%) were secondary to Candida species with 45% of these cases caused by either C. glabrata or C. krusei (Figure 2). 90% were on antifungal prophylaxis (85% fluconazole) at time of diagnosis of invasive candidiasis. All the Candida IFIs were intra-abdominal infections. Amongst the 15 non-Candida IFIs (42.9%), 9 were secondary to endemic mycoses and 4 were secondary to invasive molds. Conclusion Our study shows a high incidence of IFIs secondary to Candida, with few patients diagnosed with non-Candida IFIs (Figure 3). Non-Candida IFIs, mostly secondary to endemic mycoses, occurred more than a year after transplant. Patients are at highest risk for Candida IFIs within the first 30 days after PT, likely secondary to organ space surgical site infections, despite receipt of antifungal prophylaxis. Breakthrough invasive candidiasis occurred in 90% of cases. Though our study lacked a comparator group without prophylaxis, these data question the effectiveness of fluconazole prophylaxis after PT. Disclosures All Authors: No reported disclosures

Abstract Background Clostridioides difficile infection (CDI) is a common and potentially life-threatening infection. Transplant recipients are vulnerable to CDI due to immune suppression and frequent antibiotic exposure. CDI can lead to serious complications in these patients, including allograft failure. In a population of pancreas transplant recipients, we aimed to identify epidemiologic characteristics and risk factors associated with CDI within 90 days of transplant. Methods We performed a retrospective cohort study of adults who underwent pancreas transplantation between January 1, 2010, and December 31, 2020, at three centers in Arizona, Florida, and Minnesota. Patients were excluded if they developed pancreas allograft failure within 48 hours of transplantation. The primary outcome was diagnosis of CDI within 90 days of transplantation and the secondary outcome was pancreas allograft failure. The main analyses were performed by Cox regression. Results A total of 482 patients were included, of which 35 (7.3%) developed CDI within 90 days (Table 1). Within the subset of 35 CDI patients, the median time to CDI was 17.0 (IQR 13.0–28.5) days (Figure 1) with most (83%) diagnosed with non-severe CDI. Most patients with CDI were on current systemic antibiotics (94%), primarily for prophylaxis (73%). CDI treatment was vancomycin for the majority of patients (71%) and metronidazole for the rest (29%). One patient had a fecal transplant for recurrence, and none required surgery. In multivariable cox regression of associations with 90-day CDI, significant associations were anastomotic leak (HR 3.04, 95% CI 1.2-7.4; p=0.015) and simultaneous pancreas-kidney transplantation (HR 8.70, 95% CI 1.15-66.7; p=0.036); age (HR 0.97, 95% CI 0.94-1.01; p=0.110) was not significant. In a secondary analysis, CDI was not associated with pancreas allograft failure (p=0.719).Table 1.Characteristics of 482 patients who underwent pancreas transplantation. Conclusion This study identified preceding anastomotic leak as a risk factor for 90-day CDI after pancreas transplantation, likely due to subsequent intra-abdominal infection and antibiotic use. simultaneous pancreas-kidney transplantation is another risk factor due to additional comorbidity. Transplant providers should be cognizant of the risks of CDI and mitigate these risks as possible. Disclosures All Authors: No reported disclosures

AbstractBackgroundBK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non‐kidney transplant recipients, data are limited regarding its epidemiology and outcomes in pancreas transplant recipients.MethodsWe conducted a retrospective cohort study of adults who underwent pancreas transplantation from 2010–2020. The primary outcome was BKV DNAemia. Secondary outcomes were estimated glomerular filtration rate (eGFR) reduction by 30%, eGFR < 30 mL/min/1.73 m2, endstage kidney disease, and pancreas allograft failure. Cox regression with time‐dependent variables was utilized.ResultsFour hundred and sixty‐six patients were analyzed, including 74, 46, and 346 with pancreas transplant alone (PTA), pancreas‐after‐kidney, or simultaneous pancreas–kidney transplants, respectively. PTA recipients experienced a lower incidence of BKV DNAemia (8.8% vs. 32.9%; p < .001) and shorter duration of DNAemia (median 28.0 vs. 84.5 days). No PTA recipients with BKV DNAemia underwent kidney biopsy or developed endstage kidney disease. Lymphopenia, non‐PTA transplantation, and older age were associated with BKV DNAemia, which itself was associated with pancreas allograft failure (adjusted hazard ratio 2.14, 95% confidence interval 1.27–3.60; p = .004). Among PTA recipients, BKV DNAemia was not associated with eGFR reduction or eGFR < 30 mL/min/1.73 m2.ConclusionsBKV DNAemia was common among PTA recipients, though lower than a comparable group of pancreas–kidney recipients. However, BKV DNAemia was not associated with adverse native kidney outcomes and no PTA recipients developed endstage kidney disease. Conversely, BKV DNAemia was associated with pancreas allograft failure. Further studies are needed to estimate the rate of BKV nephropathy in this population, and further evaluate long‐term kidney outcomes.

Abstract Background Nocardia primarily infects patients who are immunocompromised or those with chronic lung disease. Although disseminated infection is widely recognized as an important prognostic factor, studies have been mixed on its impact on outcomes of nocardiosis. Methods We performed a retrospective cohort study of adults with culture-confirmed nocardiosis. Advanced infection was defined as disseminated infection, cavitary pulmonary infection, or pleural infection. The primary outcome was 1-year mortality, as analyzed by multivariable Cox regression. Results Of 511 patients with culture growth of Nocardia, 374 (73.2%) who had clinical infection were included. The most common infection sites were pulmonary (82.6%), skin (17.9%), and central nervous system (14.2%). In total, 117 (31.3%) patients had advanced infection, including 74 (19.8%) with disseminated infection, 50 (13.4%) with cavitary infection, and 18 (4.8%) with pleural infection. Fifty-nine (15.8%) patients died within 1 year. In multivariable models, disseminated infection was not associated with mortality (hazard ratio, 1.16; 95% CI, .62–2.16; P = .650) while advanced infection was (hazard ratio, 2.48; 95% CI, 1.37–4.49; P = .003). N. farcinica, higher Charlson Comorbidity Index, and culture-confirmed pleural infection were also associated with mortality. Immunocompromised status and combination therapy were not associated with mortality. Conclusions Advanced infection, rather than dissemination alone, predicted worse 1-year mortality after nocardiosis. N. farcinica was associated with mortality, even after adjusting for extent of infection. While patients who were immunocompromised had high rates of disseminated and advanced infection, immunocompromised status did not predict mortality after adjustment. Future studies should account for high-risk characteristics and specific infection sites rather than dissemination alone.

AbstractBackgroundSpecific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied.MethodsWe performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality.ResultsNine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart‐kidney (N = 1), liver‐kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152–283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim‐sulfamethoxazole (TMP‐SMX) and all patients received TMP‐SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow‐up of 1.96 (IQR 0.90–6.33) years. Two patients died during follow‐up, both without evidence of nocardiosis.ConclusionsThis study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP‐SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis. image

Background. Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis. Methods. We performed a retrospective cohort study of PT recipients from 2010–2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression. Results. Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P < 0.001). Overall, 90-d CDI was 7.4%, with no difference between prophylaxis groups (P = 0.680). SSI was associated with pancreas allograft failure or death, even after adjusting for clinical factors (HR 1.94; 95% CI, 1.16-3.23; P = 0.011). Conclusions. Perioperative prophylaxis with Enterococcus coverage was associated with reduced risk of 30-d SSI but did not seem to influence risk of 90-d CDI after PT. This difference may be because of the use of beta-lactam/beta-lactamase inhibitor combinations, which provide better activity against enteric organisms such as Enterococcus and anaerobes compared with cephalosporin. Risk of SSI was also related to anastomotic leak from surgery, and SSI itself was associated with subsequent risk of a poor outcome. Measures to mitigate or prevent early complications are warranted.

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.