Castillo, Natalia E

Abstract Background Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) is standard therapy for high-risk nonmuscle-invasive bladder cancer. However, M bovis infections can occur and are not well understood. We aimed to characterize clinical phenotypes, diagnosis, management, and outcomes of culture-confirmed M bovis BCG infections following intravesical therapy for urothelial carcinoma. Methods A retrospective single-center review of adults with culture-confirmed M bovis infection after intravesical BCG (May 2009–July 2024) was conducted, abstracting clinical, microbiologic, treatment, and outcome data. Results Twenty-two White male patients (median age, 77 years) were included; 8 (36.4%) had localized genitourinary infection, 6 (27.3%) had dissemination limited to blood, and 8 (36.4%) had dissemination to other organs. Patients with bloodstream-only infection presented acutely (median 1.5 days after last BCG), whereas those with localized or organ-disseminated disease presented months to years after BCG, with the longest diagnostic delays in organ-disseminated infection. Despite all cases had culture-proven M bovis BCG infection, acid-fast smear, Mycobacterium tuberculosis complex polymerase chain reaction, and histopathology had limited sensitivity. All isolates were susceptible to rifampin, isoniazid, and ethambutol; all were resistant to pyrazinamide. Median treatment duration exceeded 9 months, 94.7% achieved cure, and attributable mortality was 5.0% (1 vascular graft infection). Conclusions M bovis BCG infections following intravesical therapy have favorable outcomes but are often associated with diagnostic delays and prolonged treatment. Early suspicion, comprehensive diagnostic evaluation, and timely surgical source control when indicated are critical. Management strategies should be tailored based on the extent of disease dissemination and individual host factors.

Abstract Background Elizabethkingia spp. are non-enteric, gram-negative bacilli that are ubiquitous in environment. It has recently been identified as a causative pathogen in hospital outbreaks of life-threatening bloodstream infections in the Midwestern United States. Methods Retrospective electronic medical record review was performed for patients with Elizabethkingia spp. isolated from any site between November 2011 and September 2020 at our tertiary academic medical center. Antimicrobial susceptibilities are performed using Wadsworth agar dilution method. Results Fifteen cases with Elizabethkingia spp. were included. Ten patients (66.7%) were male and fourteen (93.3%) were Caucasian. The median age was 58 years (IQR 42-67). Four patients had diabetes mellitus, with two of these having end-organ damage (nephropathy, neuropathy, or retinopathy). Five patients had a tracheostomy, two patients had a history of lung transplantation, and four patients had active malignancy at the time of diagnosis (table 1). The most common clinical syndrome was respiratory infection (n=6), followed by catheter-related bloodstream infection (CRBSI) (n=4). Three patients were considered to be asymptomatically colonized. Five patients (33.3%) died, one of which was attributable to Elizabethkingia infection. A total of 55 isolates from all sites were available from the fifteen patients. The most common site of isolation was respiratory tract (23/55, 41.8%). In total, 33 of 55 isolates had polymicrobial growth, with the highest rate occurring in respiratory tract specimens (Table 2). A total of 23 clinical isolates were included in tabulation of antimicrobial susceptibility profiles; except for aztreonam (n=13). 95.7% of Elizabethkingia isolates were susceptible to trimethoprim-sulfamethoxazole, followed by levofloxacin and piperacillin-tazobactam (87% and 73.9%, respectively). All isolates were uniformly resistant to amikacin, aztreonam, and tobramycin (Table 3). Conclusion Elizabethkingia spp. can result in respiratory, bloodstream, and sinus infections especially in patients with active malignancy and tracheostomy. Amongst tested antimicrobials, trimethoprim-sulfamethoxazole showed the most favorable susceptibility profile (Figure 1). Figure 1. AN, amikacin; ATM, aztreonam; CAZ, ceftazidime; CIP, ciprofloxacin; FEP, cefepime; GM, gentamicin; LVX, levofloxacin; MEM, meropenem; NN, tobramycin; SXT, sulfamethoxazole/trimethoprim; TZP, piperacillin/tazobactam. Disclosures All Authors: No reported disclosures

Abstract Purpose To identify risk factors that may predispose patients to rifampin- and cefazolin-induced coagulopathy. Summary An 86-year-old man with a history of rheumatoid arthritis on chronic prednisone and stage 3 chronic kidney disease, notably not on warfarin, presented to the hospital with a 10-day history of right hip pain, swelling, and drainage after a recent right total-hip arthroplasty. The patient underwent a combination of surgical intervention and medication therapy with rifampin and ceftriaxone. After discharge and at postoperative day 9, ceftriaxone was changed to cefazolin due to increasing alkaline phosphatase levels. Four weeks after the initial debridement, antibiotics, and implant retention, the patient underwent a second irrigation and debridement due to persistent infection. Cefazolin and rifampin therapy was extended. Three days later, the patient presented to the emergency room with significant bleeding at the surgical site and a profoundly elevated prothrombin time and international normalized ratio (INR). No potential contributors were identified. The Naranjo adverse drug reaction probability scale identified cefazolin and rifampin as the probable cause of elevated INR. The Liverpool adverse drug reaction avoidability assessment tool classified this adverse event as “definitely avoidable.” Conclusion Rifampin-containing regimens are often recommended to treat staphylococcal prosthetic joint infections when the implant is retained. In methicillin-susceptible staphylococcal infections, cefazolin is routinely employed as the β-lactam backbone of definitive antimicrobial regimens. Although rifampin- and cefazolin-induced hypoprothrombinemia seems to be rare, adverse consequences of its occurrence may be prevented with appropriate monitoring.

Abstract Background Nocardial brain abscesses are rare, and published literature describing brain abscesses due to Nocardia species is limited to individual case reports or small series. We report one of the largest contemporary retrospective studies describing risk factors, diagnostic evaluation, management, and outcomes of nocardial brain abscess. Methods Retrospective review of all adults with brain abscess due to culture-confirmed Nocardia species at our institution between January 1, 2009, and June 30, 2020. Results Overall, 24 patients had nocardial brain abscesses during the study period. The median age at presentation was 64 years, and 62.5% were immunocompromised. Pulmonary and cutaneous infections were the most common primary sites of nocardial infection. All 24 patients had magnetic resonance imaging performed, and the frontal lobe was the most commonly involved. The most common organism isolated was Nocardia farcinica, followed by Nocardia wallacei and Nocardia cyriacigeorgica. Thirteen patients were managed with antimicrobial therapy alone, while 11 had both medical and surgical management. In all patients, dual therapy was recommended for the initial 6 weeks of treatment, and 22 patients received at least 1 oral agent as part of their final antibiotic regimen, predominantly trimethoprim-sulfamethoxazole and linezolid. Fourteen patients achieved complete clinical and radiographic resolution of infection. Conclusions Nocardia is an important cause of brain abscess in the immunocompromised host. Early diagnostic and therapeutic aspiration may help health care providers confirm the diagnosis, choose an appropriate antimicrobial regimen, and achieve source control.

Abstract Background More than 90% of reported penicillin allergies are found inaccurate when formally assessed. These allergy labels lead to decreased utilization of first-line beta-lactam antibiotics, and adverse clinical outcomes. The objective of this study was to develop a multi-disciplinary approach to decrease inaccurate labeling among hospitalized patients with documented penicillin allergy. Methods A team of clinicians, pharmacists, and nurses utilized the DMAIC quality strategy to improve accuracy of penicillin allergy labeling. Allergic reactions were stratified to develop a penicillin allergy de-labeling algorithm (Figure 1). Admission to the intensive care unit (ICU) for anaphylaxis was defined as a balancing measure. We reviewed baseline data from patients with a documented penicillin allergy admitted to a single inpatient floor at Mayo Clinic, Rochester between June and October 2019. A cause and effect diagram was used to conduct a root cause analysis. The intervention was then applied to patients who reported penicillin allergy admitted to the same floor from November 2019 to January 2020. Study data were collected and basic descriptive statistics generated. Figure 1: Penicillin allergy delabeling algorithm Results 96 patients were included in the control group with mean age of 71 years (range 65–84 years) and 55% females. Breakdown of documented allergic reactions are represented in Figure 2. 58 (60%) received an antibiotic for a median duration of 1.5 days (IQR: 0 – 6). Of these, 7(12%) received penicillin-class antibiotics, and 41 (70.6%) received non-beta-lactam antibiotics. 2 (2%) of these patients were de-labeled without any penicillin skin tests. Detailed metrics of each PDSA cycle are shown in Table 1. During PDSA cycle 2, inaccurate penicillin documentation was removed in 9/19 (47.4%) of hospitalized patients. There were no ICU admissions for anaphylaxis. Figure 2: Graphic representation of proportion of type of documented allergic reactions to penicillin Table 1: Metrics and outcomes at baseline and during successive PDSA cycles Conclusion Various factors contribute to penicillin allergy mislabeling. Our comprehensive algorithm addresses nuances of penicillin allergic reactions and increased accurate penicillin allergy labeling in 47.4% of the cases. Beta-lactam use also increased to 37% through our pilot project while maintaining patient safety. A multi-disciplinary and patient-centered approach aligned with institutional workflows is necessary to improve patient outcomes. Disclosures All Authors: No reported disclosures

Abstract Background The etiology of febrile neutropenia in patients with hematological malignancy is identified in only 20–30% of cases. Sinus computed tomography (CT) is often used, regardless of symptoms, to rule out rhinocerebral source of infection. There are no clear guidelines on when to perform sinus CT in this population. In this study, we evaluated the role of sinus CT in febrile neutropenic patients. Methods We retrospectively reviewed medical records of all adults (age ≥18 years) with febrile neutropenia (T≥ 38.3ºC, ANC < 0.5 x 109/L) and hematological malignancies who underwent sinus CT from January 2014 to May 2020. We present the preliminary analysis of the impact of sinus CT findings on the management of febrile neutropenia. Results 47 patients with a total of 56 episodes of febrile neutropenia met the inclusion criteria. The median age at presentation was 57 years (IQR: 42 - 68 years). The most common underlying malignancy was acute myeloid leukemia (51%), followed by myelodysplastic syndrome (19%). At presentation, 47% had refractory disease, 21% were newly diagnosed, 15% had relapsed, 15% were in complete remission, and 2% were in partial remission. Of the total 56 episodes, 29 (52%) had symptoms of rhinorrhea (20%), facial pain (14%), and sinus congestion (14%). The remaining 27 of 56 episodes (48%) had no sinus symptoms. Sinus CT was abnormal in 48 of 56 episodes (86%); the most common finding was mucosal thickening (47/48; 98%), followed by air-fluid levels (7/48; 14.5%), partial opacification (6/48; 12.5%), complete opacification (2/48; 4%), and bony invasion (2/48; 4%). The source of febrile neutropenia was attributed to the CT sinus findings in 9 cases (9/48; 29%), leading to a change in therapeutic management. All 9 patients were symptomatic, with evidence of necrosis in 22% (2/9) and purulence in 22% (2/9) on nasal endoscopy. Table 1 Conclusion Mucosal thickening is a frequent and non-specific imaging finding, particularly in patients without sinus symptoms. Sinus CT findings in patients with febrile neutropenia without sinus symptoms had no impact on clinical management. Consequently, sinus CT may be reserved for patients presenting with sinus symptoms. Disclosures M. Rizwan Sohail, MD, Aziyo Biologics (Consultant)Medtronic Inc (Consultant, Research Grant or Support)

AbstractBackgroundAscertaining involvement of left ventricular assist device (LVAD) in a patient presenting with bloodstream infection (BSI) can be challenging, frequently leading to use of chronic antimicrobial suppressive (CAS) therapy. We aimed to assess the efficacy of CAS therapy to prevent relapse of BSI from LVAD and non-LVAD sources.MethodsWe retrospectively screened adults receiving LVAD support from 2010 through 2018, to identify cases of BSI. Bloodstream infection events were classified into LVAD-related, LVAD-associated, and non-LVAD BSIs.ResultsA total of 121 episodes of BSI were identified in 80 patients. Of these, 35 cases in the LVAD-related, 14 in the LVAD-associated, and 46 in the non-LVAD BSI groups completed the recommended initial course of therapy and were evaluated for CAS therapy. Chronic antimicrobial suppressive therapy was prescribed in most of the LVAD-related BSI cases (32 of 35, 91.4%) and 12 (37.5%) experienced relapse. Chronic antimicrobial suppressive therapy was not prescribed in a majority of non-LVAD BSI cases (33, 58.9%), and most (31, 93.9%) did not experience relapse. Chronic antimicrobial suppressive therapy was prescribed in 9 of 14 (64.2%) cases of LVAD-associated BSI and none experienced relapse. Of the 5 cases in this group that were managed without CAS, 2 had relapse.ConclusionsPatients presenting with LVAD-related BSI are at high risk of relapse. Consequently, CAS therapy may be a reasonable approach in the management of these cases. In contrast, routine use of CAS therapy may be unnecessary for non-LVAD BSIs.