Citations

Abstract Background Invasive fungal infection (IFI) in heart transplant recipients is associated with increased mortality and poor outcome. Reports have estimated the risk of 1-year IFI to be 3.4-8.6% with renal replacement therapy, delayed chest closure, and reoperation suggested as risk factors. However, the role of antifungal prophylaxis is unclear, though previous studies have suggested a reduced incidence of invasive Aspergillosis. The transplant program in Mayo Arizona provides 6 months of universal azole prophylaxis for Coccidioides, while Rochester and Florida only provide prophylaxis to high risk patients. We sought to define epidemiology and risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. Methods We conducted a retrospective cohort study of patients undergoing single-organ heart transplantation at Mayo Rochester, Florida, or Arizona from January 2000 to March 2019. We identified baseline characteristics, details of transplant hospitalization such as need for renal replacement therapy, open chest, reoperation, and operative time, receipt of antifungal prophylaxis, and diagnosis of IFI. Multivariable Cox analysis was performed to identify risk factors of time to 1-year IFI. Results A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62) and 72% male. 444 patients received antifungal prophylaxis which included 32% fluconazole, 34% itraconazole, 18% voriconazole, 15% echinocandin, and < 1% amphotericin or posaconazole. Over 1-year follow-up, 62 patients developed IFI with a cumulative prevalence of 6.4%. The most common organisms were Aspergillus (50%) and Candida (27%). In a multivariable model, factors associated with 1-year IFI were post-transplant renal replacement therapy (HR 3.34, 95% CI 1.69-6.60; P < 0.001) and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96; P=0.042). Operative time, recent hospitalization, open chest, and post-transplant mechanical circulatory support were not associated with 1-year IFI. Conclusion Renal replacement therapy after transplantation is associated with 1-year IFI. Antifungal prophylaxis appears to be protective and further prospective study is warranted to verify this finding. Disclosures All Authors: No reported disclosures

Abstract Background Stenotrophomonas maltophilia is a gram-negative, opportunistic infection that is usually hospital-acquired and associated with high morbidity and mortality. The reported increase in S. maltophilia infections is presumed to be due to an increase in the population at risk. Methods We retrospectively reviewed 10-year data for S. maltophilia bacteremia in hospitalized adults at our institution to determine the population at risk, sources of infection, common complications, antimicrobial susceptibility profiles, and clinical outcome trends over the past decade. Results Among the 98 patients analyzed, the most common source of infection was catheter-related (62, 63.3%). Most isolates (61, 65%) were resistant to ceftazidime; fewer were resistant to trimethoprim-sulfamethoxazole (TMP-SMX; 2, 2.1%) and levofloxacin (22, 23.4%). All-cause in-hospital mortality was 29.6% (29 patients). The highest mortality, 53.8%, was observed in pulmonary sources of bacteremia. Conclusions Although TMP-SMX continues to have reliable activity in our cohort, we noted resistance to TMP-SMX in patients with recent TMP-SMX exposure, including a case with developing resistance to TMP-SMX while on therapy.

Abstract Background Optimum duration of antimicrobial therapy for acute bacteremic cholangitis is not well established; however, 4–7 days is recommended by the 2018 Tokyo guidelines in those without Gram-positive bacteremia. Methods A retrospective study performed at Mayo Clinic - Rochester, Florida and Arizona sites was conducted, reviewing all adult patients with the first episode of acute cholangitis secondary to biliary stone obstruction, between January 1, 2012 and December 31, 2017. We reviewed the duration of prescribed antimicrobials. Results Among 331 included cases, 197(60%) were men, 66 (20%) were immuno-compromised. Presenting symptoms included fever in 202 (61.5%), abdominal pain in 289 (87%), jaundice 128(38.7%), and altered mentation in 49 (15%). Among these, 256 (77%) were classified as “definite” and 38 (11.5%) were “suspected” using the 2018 Tokyo guideline classification. Cholangitis grade was grade III in 134 (40.5%); grade II in 115 (34.7%); and grade I in 82 (24.8%). Majority of cases, 321 (97%), underwent source control—most commonly 309 (96%) achieved by endoscopic retrograde cholangiopancreatography (ERCP). Source control occurred within 24 hr of presentation in 197 (61.4%) of the cases. Bacteremia was documented in 131/277 (47%). Majority of bacteremias were due to Gram-negative organisms in 119 (91%). Mean duration of antibiotic therapy following “source control” was 9.6 days (SD 7.0). Cases with bacteremia, resulted in longer treatment duration, mean of 13 days (SD 5.6), regardless of the isolated organism. Overall 30 day mortality was 14/331 (4.2%). No mortality difference was noted in patients who underwent early (within 12 hours) vs. later source control (4.55% Vs. 4.53%), nor in those who received more or less than 6 days of antibiotic therapy after source control (4.7% Vs. 3.9%, P = 0.76). No difference in mortality was observed in those with or without bacteremia. Conclusion Our results note the use of longer courses of antimicrobials for management of bacteremic cholangitis, regardless of the organism type. This population could be a prime target for an antimicrobial stewardship intervention, to decrease the duration of prescribed antimicrobials in accordance with recent guidelines. Disclosures All authors: No reported disclosures.

Abstract Background Stenotrophomonas maltophilia is a hospital acquired infection that is associated with high morbidity and mortality. There has been a reported rise in S. maltophilia infections, presumed secondary to the increase in the population at risk. Methods We retrospectively reviewed all hospitalized adult patients in Mayo Clinic, MN with S. maltophilia bacteremia from January 2008 through January 2018. We analyzed patient population and described patients at risk, sources of infection, and changes in antimicrobial susceptibility profile. Results A total of 94 patients were analyzed, including 52 males, median age of 56 (46–65.75 IQR). The population included 60 infections in those with malignancies and 30 infections in transplant recipients. At presentation, 58 (61.7%) were febrile, while 54 (58.1%) presented with hemodynamic instability. Majority (70.2%) received broad-spectrum antimicrobials within 2 weeks of presentation. The most common source was catheter associated infection (n = 60), 15 cases were secondary to gastrointestinal, and 9 due to a pulmonary source. Almost half, 46 (48.9%) required ICU admission. Two patients were diagnosed with endocarditis. Most isolates, 61(64.9%), were resistant to ceftazidime, 2 (2.2%) resistant to TMP/SMX and 20 (21.5%) were resistant to levofloxacin. Exposure to a quinolone in the 30 days prior to presentation did not impact fluoroquinolone resistance. Five patients were exposed to Trimethoprim/Sulfamethoxazole (TMP/SMX) in the 30 days prior to presentation, which was associated with higher rate of TMP/SMX resistance compared with those without exposure (80% vs. 98.8%, P = 0.004). Treatment options commonly included combination therapy, and TMP/SMX was a primary agent used in the majority, 59 (62.8%). All-cause in-hospital mortality was 26.6%. All-cause mortality was lower for line associated infections (16.67%) vs. other sources (44.12%) with P = 0.0038. Conclusion S. maltophilia bacteremia should be considered in hospitalized patients with recent use of broad-spectrum antibiotics. Although TMP/SMX continues to have reliable activity, use of empiric ceftazidime pending susceptibility testing should be avoided as trend toward increasing resistance is noted. We noted a drop in TMP/SMX susceptibility in those with recent reported TMP/SMX use. Disclosures All authors: No reported disclosures.

AbstractTo the best of our knowledge, we report the first case of pre‐transplant unrecognized disseminated Coxiella burnetii infection, unmasked in the post‐transplant period leading to both heart and kidney allograft dysfunction. A 59 year old man with a history of simultaneous heart‐kidney transplantation due to end stage heart failure from severe aortic regurgitation (AR) and cryoglobulinemic immune complex mediated concentric necrotizing glomerulonephritis (GN), presents with a history of intermittent fevers and fatigue. Prior to transplantation he was treated for multiple episodes of culture negative endocarditis requiring bio‐prosthetic valve replacement. Evaluation of fever included a transesophageal echocardiogram (TEE) that revealed a large hyperechoic mass on the anterior mitral leaflet with perforation, severe mitral regurgitation and moderate AR. Blood cultures were negative at that time. Owing to development of allograft mitral and aortic valve insufficiency, he underwent allograft bio‐prosthetic mitral valve (MV) replacement and aortic valvuloplasty 2 years following his transplantation. Pathologic examination of the allograft mitral valve demonstrated fibrinopurulent exudate with degenerating bacterial organisms, consistent with vegetation and myxoid degenerative changes. Due to a high suspicion for native heart C. burnetii prosthetic valve endocarditis prior to transplantation, we re‐evaluated the native explanted heart histopathology, as well as the explanted allograft MV. Cardiac allograft and native MV were positive for C. burnetii by real‐time PCR. C. burnetii serology was consistent with persistent infection as well.

AbstractCytomegalovirus (CMV) pneumonia causes major morbidity and mortality. Its diagnosis requires demonstration of viral cytopathic changes in tissue, entailing risks of lung biopsy. This study aimed to determine CMV viral load (VL) thresholds in bronchoalveolar lavage fluid (BALF) for diagnosis of CMV pneumonia in immunocompromised patients. CMV VL in BALF was studied in 17 patients (83% transplant recipients) and 21 control subjects with and without CMV pneumonia, respectively, using an FDA‐approved PCR assay (Cobas® AmpliPrep/Cobas TaqMan® CMV Test, Roche Molecular Systems, Inc.) calibrated to the WHO International Standard for CMV DNA (NIBSC: 09/162). Receiver operating characteristic curve analysis produced a BALF CMV VL threshold of 34 800, IU/mL with 91.7% sensitivity and 100.0% specificity for diagnosis of possible, probable, and proven CMV pneumonia in transplant patients, while a threshold of 656 000 IU/mL yielded 100% sensitivity and specificity among biopsy‐proven cases. For all immunocompromised patients, a VL threshold of 274 IU/mL was selected. VL thresholds also were normalized to BALF cell count yielding a threshold of 0.32 IU/106 cells with 91.7% sensitivity and 90.5% specificity for possible, probable, and proven CMV pneumonia in transplant recipients. Monitoring CMV VL in BALF may be a less invasive method for diagnosing CMV pneumonia in immunocompromised patients.