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Soluble products spontaneously secreted by murine nuclear erythroid cells directly suppress the proliferation of activated B-lymphocytes induced by bacterial lipopolysaccharides. Blocking of the transforming growth factor-β synthesis in nuclear erythroid cells by antisense oligonucleotides binding mRNA and blocking of this factor's functional activity by neutralizing antibodies were associated with a marked decrease in suppressor activity of the medium conditioned by nuclear erythroid cells. [ABSTRACT FROM AUTHOR]

Background Overexpression of interleukin (IL)-1β has been described in solid tumors, including lung. IL-1β can promote angiogenesis, tumor invasiveness, and induces tumor-associated immunosuppression through myeloid-derived suppressor cell (MDSC) accumulation in tumors. Pre-clinical data has shown that IL-1β inhibition reduced tumor growth, by limiting pro-tumorigenic inflammation and polarization of MDSCs into M1 phenotype. Canakinumab is a human monoclonal antibody with high affinity and specificity for IL-1β. Recently, it was found that canakinumab was associated with a significant and dose-dependent reduction in incidence and mortality from lung cancer based on CANTOS study. Trial design CANOPY-A (NCT03447769) is a phase III, randomized, double-blind, placebo-controlled study designed to evaluate efficacy and safety of adjuvant canakinumab vs placebo in pts with surgically resected NSCLC. This trial will enroll adult pts, with completely resected (R0) AJCC/UICC v.8 stages II-IIIA and IIIB (T > 5 cm and N2) NSCLC, who have completed standard-of-care adjuvant treatments, including cisplatin-based chemotherapy and mediastinal radiation therapy (if applicable). Prior treatment with neoadjuvant chemotherapy or neoadjuvant radiotherapy is not permitted. Approximately 1500 pts will be randomized 1:1 to receive canakinumab (200 mg Q3W, s.c) or placebo (Q3W, s.c.) for 18 cycles or until disease recurrence, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or pt, death, or loss to follow-up. Randomization will be stratified by AJCC/UICC v.8 stage, tumor histology, and region. In the amended protocol, a sub-study was included to determine the biomarker levels in the blood at pre- and post-surgery, and to establish their association with canakinumab efficacy. The primary objective is disease-free survival (per investigator assessment). Secondary objectives include overall survival (key secondary objective), lung cancer-specific survival, safety, pharmacokinetics and immunogenicity of canakinumab, and pt-reported outcomes. Enrollment is ongoing. Clinical trial identification CACZ885T2301. Legal entity responsible for the study Novartis. Funding Novartis. Disclosure B.C. Cho: Honoraria (self): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD; Advisory / Consultancy: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD; Research grant / Funding (self): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD; Shareholder / Stockholder / Stock options: TheraCanVac Inc; Licensing / Royalties: Champions Oncology. G-C. Chang: Honoraria (self): F. Hoffmann–La Roche, Ltd, Eli Lilly and Company Oncology, AstraZeneca, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, and Merck Sharp & Dohme. Y-C. Kim: Honoraria (self): AstraZeneca, Roche, Boehringer Ingelheim; Research grant / Funding (self): AstraZeneca, Roche, Boehringer Ingelheim. S. Geater: Honoraria (self): AstraZeneca, Boehringer Ingelheim, Roche; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca, Boehringer Ingelheim, Roche, MSD; Travel / Accommodation / Expenses: AstraZeneca, Boehringer Ingelheim, Roche. S. Saeteng: Honoraria (self): AstraZeneca, Novartis : Speaker. Y. Goto: Speaker Bureau / Expert testimony: AstraZeneca, Eli Lilly, Chugai, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, Bristol-Myers Squibb, Pfizer, MSD, Shionogi Pharma, Novartis; Advisory / Consultancy: Eli Lilly, Chugai, Taiho Pharmaceutical, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Glaxo Smith Kline; Research grant / Funding (self): AbbVie, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Pfizer, Novartis, Kyorin. S. Lu: Research grant / Funding (self): AstraZeneca, Hutchison, Roche; Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma, Simcere, Roche; Honoraria (self): AstraZeneca, Roche. A. Ardizzoni: Advisory / Consultancy: MDS, Roche; Honoraria (self): MSD, BMS, Pfizer, Lilly; Research grant / Funding (self): BMS, Celgene, Roche; Leadership role: Member Educational Committee. F. Barlesi: Honoraria (self): AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology,. P. De Marchi: Advisory / Consultancy: Roche, Bayer, Msd, BMS, Pfizer, AstraZeneca; Speaker Bureau / Expert Testimony: Roche, Bayer, MSD, BMS, Pfizer, AstraZeneca; Travel / Accommodation / Expenses: Roche, MSD, BMS, AstraZeneca. L. Paz-Ares: Advisory / Consultancy: Roche, Lilly, Novartis, Pfizer, BMS, MSD, Takeda, AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Celgene; Honoraria (self): Roche, Lilly, Novartis, Pfizer, BMS, MSD, Amgen, Merck, Sanofi, Takeda, AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, PharmaMar, Celgene. D.R. Spigel: Advisory / Consultancy: AbbVie (Inst); Amgen (Inst); AstraZeneca (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squibb (Inst); Celgene (Inst); Evelo Therapeutics (Inst); Foundation Medicine (Inst); Genentech/Roche (Inst); GlaxoSmithKline (Inst); Illumina (Inst); Lilly (Inst); Research grant / Funding (institution): AbbVie (Inst); Acerta Pharma (Inst); Aeglea Biotherapeutics (Inst); Amgen (Inst); ARMO BioSciences (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squibb (Inst); Celgene (Inst); Celldex (Inst); Clovis Oncolog; Travel / Accommodation / Expenses: AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; EMD Serono; Genentech; Genzyme; Intuitive Surgical; Lilly; Merck; Pfizer; Purdue Pharma; Spectrum Pharmaceuticals; Sysmex. M. Thomas: Advisory / Consultancy: Novartis, Lilly, Pfizer, Bristol-Myers Squibb, Roche, AstraZeneca, Boehringer Ingelheim, MSD; Honoraria (self): Roche, Bristol-Myers Squibb, Lilly, AstraZeneca, Novartis, Pfizer, Boehringer Ingelheim, MSD; Research grant / Funding (self): Roche, BMS, MSD, AstraZeneca, Takeda. E.B. Garon: Advisory / Consultancy: Dracen, EMD Serono; Research grant / Funding (self): AstraZeneca, BMS, Eli Lilly, Genentech, Merck, Novartis, Neon, Iovance, Dynavax, Mirati. M. Leung: Shareholder / Stockholder / Stock options: Novartis; Full / Part-time employment: Novartis. J. Baum: Shareholder / Stockholder / Stock options: Novartis stock; Full / Part-time employment: Novartis. Spouse (Lauren Baum) – Abbot Laboratories. Z. Zewen: Full / Part-time employment: Novartis; Shareholder / Stockholder / Stock options: Novartis. B. Mookerjee: Full / Part-time employment: Novartis; Shareholder / Stockholder / Stock options: Novartis, GlaxoSmithKline, Incyte, AstraZeneca. J.C-H. Yang: Advisory / Consultancy: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai Pharmaceutical, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceuticals, Daiichi-Sankyo, Hansoh Pharmaceuticals, Takeda Pharmaceuticals, Bluep; Honoraria (self): Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai Pharmaceutical, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceuticals, Daiichi-Sankyo, Hansoh Pharmaceuticals, Takeda Pharmaceuticals, Bluep; Leadership role: IASLC CME activity: Author/Board of Directors/Presenter/Reviewer. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background mMCC is a rare, highly aggressive neuroendocrine cancer of the skin with a poor prognosis. ICIs have favourable efficacy and safety in clinical trials. We outline single centre experience utilising ICIs in mMCC. Methods Medical records of patients (pts) with mMCC treated with ICIs from Aug 2015 to Dec 2018 at Peter MacCallum Cancer Centre in Australia were retrospectively analysed. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples were performed. Baseline tumor volumes and responses were assessed with FDG-PET scans using the Hicks criteria. Results 23 pts with mMCC were treated with ICIs. Pt characteristics are summarised in the table. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%); 10 (44%) complete metabolic responses (CMR) and 4 (17%) partial metabolic responses (PMR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival (PFS) rate was 39%. Increased OR were seen in pts aged less than 75 (OR 8/10, 80% vs 46%), pts with normal baseline LDH (OR 5/7, 71% vs 50%), pts with an immune-related adverse event (irAE) (OR 6/6, 100% vs 47%) and in MCPyV negative pts (OR 11/16, 69% vs 43%). Pts with a CMR had lower mean-tumor volume on baseline FDG-PET scan (CMR: 35.7mL, no CMR: 187.8mL, p = 0.05). No correlation was seen between tumor PD-L1 positivity and response to ICI (p = 0.25) or MCPyV status (p = 0.76). Similarly, no association was seen between OR and CD3 staining within the tumor (p = 0.07). 10 pts received radiation (RT) during ICI: 4 pts started RT concurrently (OR 75%, CMR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. 6 pts (26%) had a Grade 1-2 irAE. Table: 341O Baseline characteristics Patient Characteristics  n = 23  Age (years) Median (range)  75 (64 to 91)  Gender Male Female  18 5  ECOG 0 12 3  8 12 3  ICI Avelumab Pembrolizumab Other (BGB-A317)  15 5 3  MCPyV status Positive Negative  7 16  Visceral disease  17  Prior chemotherapy  10  History of autoimmune disease  2  Previous immunosuppression  2  Patient Characteristics  n = 23  Age (years) Median (range)  75 (64 to 91)  Gender Male Female  18 5  ECOG 0 12 3  8 12 3  ICI Avelumab Pembrolizumab Other (BGB-A317)  15 5 3  MCPyV status Positive Negative  7 16  Visceral disease  17  Prior chemotherapy  10  History of autoimmune disease  2  Previous immunosuppression  2  Table: 341O Baseline characteristics Patient Characteristics  n = 23  Age (years) Median (range)  75 (64 to 91)  Gender Male Female  18 5  ECOG 0 12 3  8 12 3  ICI Avelumab Pembrolizumab Other (BGB-A317)  15 5 3  MCPyV status Positive Negative  7 16  Visceral disease  17  Prior chemotherapy  10  History of autoimmune disease  2  Previous immunosuppression  2  Patient Characteristics  n = 23  Age (years) Median (range)  75 (64 to 91)  Gender Male Female  18 5  ECOG 0 12 3  8 12 3  ICI Avelumab Pembrolizumab Other (BGB-A317)  15 5 3  MCPyV status Positive Negative  7 16  Visceral disease  17  Prior chemotherapy  10  History of autoimmune disease  2  Previous immunosuppression  2  Conclusions ICIs showed efficacy and safety consistent with trial data. Younger age, negative MCPyV status, normal LDH, lower baseline FDG-PET tumor volume and irAEs are potentially associated with enhanced response. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure R.J. Hicks: Shareholder / Stockholder / Stock options: Telix Pharmaceuticals; Travel / Accommodation / Expenses: Endocyte; Travel / Accommodation / Expenses: GE Medical Systems. R. Tothill: Honoraria (self), Travel / Accommodation / Expenses: Merck Serono. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background VEGF and Ang2 signaling have key functions in tumor angiogenesis and have an immunosuppressive effect in the tumor microenvironment. Preclinical data show that combined inhibition of VEGF/Ang2 and PD-1 enhances the tumor microenvironment to support T-cell mediated destruction of tumor cells. BI 836880 is a humanized bispecific nanobody that targets VEGF and Ang2, and BI 754091 is an anti-PD-1 antibody. Each have shown safety and preliminary activity as monotherapy in phase I (recommended phase 2 dose [RP2D] 720 mg intravenous [iv] every 3 weeks [q3w] for BI 836880 [Caucasian pts] and 240 mg iv q3w for BI 754091 [Caucasian and Japanese pts]). An ongoing phase Ib study (NCT03468426) will determine the RP2D, safety and preliminary activity of BI 836880 + BI 754091 in Caucasian pts. The current phase I study will determine the maximum tolerated dose (MTD)/RP2D of BI 836880 alone or in combination with BI 754091 in Japanese pts with advanced solid tumors. Trial design This open-label, multi-center, dose-escalation trial will enroll pts with a confirmed diagnosis of advanced, unresectable and/or metastatic solid tumors (any type) whose disease is not amenable to standard therapies or where there is no therapy of proven efficacy. Pts are required to have an ECOG PS ≤ 1 and adequate organ function. The study has 2 parts: Part 1 will assess BI 836880 monotherapy and Part 2 will assess BI 836880 + BI 754091. Pts will receive BI 836880 at a starting dose of 360 mg iv q3w in Part 1 and of 120 mg iv q3w in Part 2 (in combination with BI 754091 240 mg iv q3w). Administration will continue until progressive disease, unacceptable toxicity or other withdrawal criteria. Dose escalation will be guided by Bayesian logistic regression models with overdose control in both Parts, with oversight from a safety monitoring committee. Primary endpoint is MTD/RP2D of BI 836880 alone (Part 1) and in combination with BI 754091 (Part 2). Secondary/further endpoints will document the safety, pharmacokinetics, anti-tumor activity and immunogenic response of BI 836880 alone and in combination with BI 754091. It is planned to enroll 24 pts. Clinical trial identification NCT03972150. Legal entity responsible for the study Boehringer Ingelheim. Funding Boehringer Ingelheim. Disclosure K. Yamazaki: Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony: Yakult; Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Lily; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Merck-Serono; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Bristol-Myers Squibb. T. Shimizu: Honoraria (self): Clinical Research Joint Scientific Committee Review Member for Phase 1 trials in Hong Kong; Honoraria (self): HKSAR China ; Advisory / Consultancy, Research grant / Funding (institution): Takeda Oncology; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Chordia Therapeutics; Research grant / Funding (institution): 3D-Medicine; Research grant / Funding (institution): Symbio Pharmaceuticals; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Five Prime; Research grant / Funding (institution): AstraZeneca ; Research grant / Funding (institution): AbbVie. T. Takahashi: Honoraria (self), Research grant / Funding (institution): AstraZeneca KK; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan K.K.; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): MSD K.K.; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim Japan, INC; Honoraria (self): Roche Diagnostics K.K.; Research grant / Funding (institution): Pfizer Japan Inc. Y. Tanaka: Full / Part-time employment: Boehringer Ingelheim. H. Myobudani: Full / Part-time employment: Boehringer Ingelheim. N. Yamamoto: Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy: Otsuka; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy: Cimic; Advisory / Consultancy, Research grant / Funding (institution): Chugai; Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ono; Speaker Bureau / Expert testimony: Sysmex; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Kyowa-Hakko Kirin; Research grant / Funding (institution): Janssen Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Merck. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Lower respiratory tract infections (LRTIs) are one of the most common infectious disease-related emergency department (ED) visits in the United States. The ID Society of America and the Agency for Healthcare Research and Quality support the use of procalcitonin (PCT) for antimicrobial stewardship (ASP) in LRTI. Though not widely available, awareness and access to PCT is rising. At our facility, PCT became available in February 2018. The aim of our study is to assess the impact of PCT at an urban community hospital and identify possible targets for ASP interventions. Methods Retrospective review of cases from February to August 2018. Cases from the ED were selected for review. Appropriateness of testing was assessed, defined as guideline-based use for cessation of antibiotics in uncomplicated LRTIs without critical illness or immunosuppression. Demographic variables and clinical characteristics, such as, diagnosis, antimicrobial use and PCT levels were obtained. Results PCT was ordered 268 times hospital-wide, of which 160 (60%) were in the ED. Ages ranged from 0–90, with an average of 47. Most cases were male (51%). Appropriate testing for LRTI occurred in 33 (29%) cases. Antimicrobials were used in 75% of cases with low (< 0.5) PCT levels (Figure 1). Length of stay (LOS) was higher in groups that received antimicrobials (Figure 2). Testing was not appropriate in 127 cases (71%), with upper respiratory (21%), soft-tissue (17%), genitourinary (15%) and abdominal (13%) infections as the most common reasons for testing. Other diagnosis included alcohol withdrawal, seizures and altered mental status. Cumulative cost of PCT testing was $24000, of which $19050 was not consistent with guidelines. Conclusion Clinicians routinely ordered PCT in the ED. Antimicrobials were used for LRTIs despite low PCT levels. This may have contributed to higher LOS and excess antimicrobial use. Unwarranted PCT testing had a cost of $19050. As PCT becomes widely available in hospitals across the United States, education and decision support by ASP to clinicians may be needed to enhance guideline-appropriate evidence-based use of PCT. Targeted ASP interventions in the ED may have cost savings by reducing excess testing, length of stay and improving antimicrobial use. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The factors that influence influenza viral load are poorly understood, but may have important implications for viral transmission and disease severity. We explored the relationship between patient and virus factors on influenza viral load across 4 consecutive influenza seasons. Methods Adult influenza-positive patients presenting to emergency departments in Baltimore, MD and Taipei, Taiwan between 2014 and 2018 were consented and enrolled. Nasopharyngeal (NP) samples and detailed paired data on symptom duration, demographics, and vaccination were collected. Viral load was inferred using the cycle threshold (Ct) values from quantitative real-time RT–PCR assays for 299 samples and influenza subtype was determined. Bivariate and multivariate analyses were conducted. Results Viral load was impacted by both patient and virus characteristics. Older age and shorter duration of symptoms was associated with a higher viral load (age: Ct difference -0.04, P = 0.022. symptoms: each increasing day, Ct difference +1.02, P < 0.001). Seasonal variability was observed, with the highest viral load associated with the 2014–2015 predominant H3N2 subtype (Ct 21.69, P < 0.001), where there was also a vaccine mismatch. Across seasons, H1N1 was associated with a lower viral load than H3N2 (Ct value + 2.66, P < 0.001). There was not association between gender and immunosuppression on viral load. Conclusion Our study demonstrates that both host and virus factors that can affect Ct values and inferred viral loads. As anticipated, higher viral load, were found to be associated with older age and shorter duration of symptoms; interestingly infection with the H3N2 subtype, traditionally associated with more severe disease was also associated with higher viral loads. Future-focused studies are required to better characterize these relationships, and directly evaluate relevance to both transmission and disease severity. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Cytomegalovirus (CMV) is an important opportunistic pathogen in liver transplant recipients (LTR). Risk of invasive disease is determined by CMV donor/recipient (D/R) serostatus, immunosuppression, and use of antiviral prophylaxis. Viral replication kinetics that can predict the development of CMV disease in transplant recipients are a high maximal viral load (VL) and a fast replication velocity. At our institution LTR at intermediate risk for CMV disease (CMV D/R+) are managed following a preemptive therapy algorithm (the pre-established cutoff for treatment initiation is 4,000 IU/mL). The primary endpoint of this study was to determine the incidence of early CMV disease in CMV D/R+ LTR. Secondary endpoints were to calculate the period of maximal VL and viral kinetic parameters. Methods We performed a retrospective observational study of CMV D/R+ LTR. Patients were followed for 6 months after transplantation. We calculated the incidence of CMV disease. Viral kinetic parameters calculated were the VL duplication time (Td) and the basic reproductive number (R0). For the assessment of viral kinetics we used the maximal VL of 10 patients who had a VL determined within the previous week. Results Forty CMV D/R+ LTR were included. The median age was 52 years, 65% were women. The mean MELD score was 18, 83% of patients had decompensated cirrhosis. No patient developed CMV disease during the first 6 months after LT. Nineteen patients (47%) had CMV DNAemia, but only 8 (20%) required antiviral therapy. The highest VLs were observed during the second month after transplant. The median duplication time was 2.14 days. The median R0 was 1.46. Conclusion Although limited by our sample size, our algorithm appears useful for discriminating the patients who need antiviral treatment from those who will only have asymptomatic DNAemia. The study population VL, Td and R0 behave as described by other groups, which emphasizes the need for frequent monitoring. This is a challenge for CMV prevention in resource-limited countries. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Reactivation of BK polyomavirus (BKPyV) due to immunosuppression after renal transplantation can lead to allograft nephropathy (BKAN) or even allograft loss. Many transplant centers implement screening protocols in an attempt to detect BKPyV reactivation before progression to BKAN, although the frequency and duration of screening vary widely among centers. Methods The New England BK Consortium (NEBKCON), a collaboration of 12 transplant centers in the northeastern United States, has adopted a standard BKPyV screening protocol (screening monthly for the first 6 months followed by screening every 3 months until 2 years after transplantation). Participating members implemented this screening protocol at their centers, and later measured adherence to the protocol as part of a NEBKCON quality improvement project. This study retrospectively analyzes BKPyV-specific outcomes in association with adherence to this protocol. Results Six centers reported data on 472 subjects who received a renal transplant between January 2016 and December 2017. Adherence to the screening protocol during the first 12 months (7.1–76.7%, mean 56.1%) and 24 months (2.9–52.5%, mean 36.8%) after transplant varied between centers. Rates of BKPyV viremia (3.6–28.2%, mean 20.6%) as well as BKAN (0–4.5%, mean 3.2%) also varied among centers. Adherence to the screening protocol was associated with a decrease in the magnitude of the initial viral load detected (3.29 vs. 3.74 log10 copies/mL, P = 0.065), but was not associated with peak viral load (3.95 vs. 4.14 log10 copies/mL, P = 0.47), viremia duration (179 vs. 196 days, P = 0.74), or incidence of BKAN among viremic subjects (15.3 vs. 16.0%, P = 0.91). Conclusion Even with a uniform screening protocol for BKPyV in place, adherence to this protocol varied widely among centers. More research is needed to determine patient-level and center-level barriers to adherence, as well as to determine optimal screening practices to further reduce the incidence of BKAN. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Cytomegalovirus (CMV) causes morbidity in kidney transplant (KT) recipients. Strategies to prevent this infection in resource-limited settings have been unreliably implemented and under-explored. We investigated CMV prevention strategies utilized among transplant centers in Thailand. Methods A questionnaire on CMV prevention strategies for KT recipients was developed using a web-based electronic survey website (www.surveymonkey.com). The survey was delivered to 31 transplant centers in Thailand. One infectious disease physician (ID) and one nephrologist (NP) from each center were included. Results There were 43 respondents from 26 (84%) transplant centers including 26 (60%) IDs and 17 (40%) NPs. The majority worked in a public hospital setting (63%) and had encountered KT recipients for at least 2 years (74%). Forty-one (98%) physicians agreed on the necessity of CMV prevention. Of these, 34 (81%) physicians implemented prevention strategies for their patients. Interventions included preemptive approaches (47%), prophylaxis (44%), hybrid approaches (3%); surveillance after prophylaxis (3%), and CMV-specific immunity-guided approaches (3%). For CMV-seropositive KT recipients, use of preemption (84%) exceeded prophylaxis (12%). However, 81% of the former preferred targeted prophylaxis in patients receiving anti-thymocyte globulin therapy. Sixty-five and 93% of physicians started preemptive therapy when plasma CMV DNA loads reached 2,000 and 3,000 copies/mL (1,820 and 2,730 IU/mL), respectively. A significantly greater percentage of NPs initiated preemptive therapy at a plasma CMV level of 1,820 IU/mL compared with IDs (88% vs. 50%, [ P = 0.02]). The most common barrier to prevention strategy implementation was financial inaccessibility of oral valganciclovir (67%) and quantitative CMV DNA testing (12%). The majority (81%) felt that a guideline would allow physicians to implement CMV prevention strategies for their patients. Conclusion Most physicians agreed on a need for preemptive approaches, although prophylaxis was targeted in those receiving intense immunosuppression. Guidelines and financial accessibility could improve CMV prevention strategy implementation in Thai KT recipients. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Immunocompromised patients are very susceptible to pulmonary aspergillosis causing 50% mortality with present treatments, indicating a need for improved therapy. To address this, we standardized a nebulization method for effectively delivering liposomal amphotericin B (AmBisome®, AmBi) into lungs of Aspergillus fumigatus-infected mice. Methods AmBi particle characterization was done with a Cascade particle impactor and a Schuco S5000 nebulizer containing 1.33 mg/mL AmBi. For in vivo studies, AmBi was nebulized (neb) into a 12 compartment chamber (one mouse/compartment), following immunosuppression with 28 mg/kg triamcinolone IP (d-3, -1, +1). Mice were challenged d0 with 9 x 106 A. fumigatus (ATCC#13073) and 4 hours post-challenge, divided into 5 groups (n = 12/gp): 5 days of 20 min/day neb AmBi (Gp1), 5 days of 10 min/day neb AmBi (Gp2), 20 min/day neb AmBi days 0, 1, 3, 5, 7 (Gp 3), 5 days of intravenous(IV) AmBi 7.5 mg/kg/day (Gp4) and IV PBS (Gp5). Seven mice/gp were monitored for survival to d21 and lungs, livers, kidneys, spleens (5 mice/gp) analyzed for mean amphotericin B µg/g and CFU/g. Results 87% of neb AmBi particles were between 0.43 mm to 3.3 mm allowing for drug penetration into 1°, 2° and terminal bronchi, bronchioles, and alveoli. This resulted in very good protection, with 20 min daily neb treatments (Gp1) giving 100% survival and 10 min daily neb treatments producing 71% survival (Gp2). There were no survivors in the PBS gp (P < 0.02 vs. Gp1 and Gp2). Every other day neb AmBi or daily IV AmBi was less effective (43% survival). In addition, neb AmBi for 20 min (Gp1) yielded significantly lower fungal burden in lungs vs. all other AmBi treatments (P < 0.02). While drug was detected in lungs of mice given 20 min of neb AmBi (2.6 µg/g), there was no drug detected in livers, kidneys or spleens of any mice given neb AmBi. In comparison, with IV AmBi, drug was detected in the lungs (7 µg/g), livers (204 µg/g), kidneys (38 µg/g), and spleens (114 µg/g). Conclusion Daily AmBi nebulization was an effective and potentially less nephrotoxic treatment for murine pulmonary aspergillosis since it achieved significantly lower tissue fungal burden and much better survival vs. daily IV AmBi, without delivering drug to the kidneys. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Optimal treatment of meningitis relies on prompt diagnostic evaluation and initiation of appropriate antimicrobials. The meningitis/encephalitis panel (MEP) is a multiplex rapid polymerase chain reaction, with the ability to detect 14 community-acquired pathogens in 1 hour. The purpose of this study was to evaluate impact of the MEP on de-escalation of antimicrobials in adult inpatients with suspected meningitis at a large community teaching hospital. Methods This single-center retrospective quasi-experimental pre/post study included adults admitted for ≥48 hours and initiated on antimicrobial therapy for suspected meningitis. Those with healthcare-associated meningitis, immunosuppression, initiation of antimicrobials >8 hours prior to lumbar puncture (LP), and use of antimicrobials for another indication were excluded. The pre-group included patients admitted prior to MEP introduction. The post-group included patients with the MEP performed. An antimicrobial stewardship bundle consisting of a meningitis order set, provider education, and use of a real-time meningitis alert in clinical decision support software was also implemented in the post-group. The primary outcome was percentage of patients experiencing antimicrobial de-escalation ≤48 hours after LP. Secondary outcomes included time to de-escalation, total duration of antimicrobial therapy (DOT), and hospital length of stay (LOS). Results A total of 45 patients were included in the study (23 pre-group and 22 post-group). Baseline characteristics were similar between groups. The percentage of patients experiencing de-escalation of antimicrobials ≤ 48 hours after LP increased by 44% in the post-group (82% vs. 38%, P = 0.005). The overall median time to de-escalation of antimicrobials decreased by 35 hours [11.1 (IQR 5.6, 17.6) vs. 46.1 (IQR 18.4, 66.5); P = 0.002] and the median time to de-escalation after LP decreased by 38 hours [13.6 (IQR 8.3, 20.3) vs. 51.6 (IQR 44.2, 69.8); P < 0.001]. No statistically significant difference in hospital LOS or total DOT was seen. Conclusion Implementation of the MEP and antimicrobial stewardship bundle increased the percentage of patients de-escalated in 48 hours and decreased the time to de-escalation. However, this did not impact the total DOT or hospital LOS. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Tuberculosis (TB) is considered as a challenging issue in solid-organ transplant recipients because of high morbidity and mortality. Active TB after transplant can occur from reactivation of latent infection or newly acquired from community. Understanding risk factors and clinical information of TB may provide an appropriate prevention and treatment strategies in this specific patient population; however, most of data were from non-endemic countries. Methods A single-center, matched case–control study was conducted in our institute. Cases were defined as newly diagnosed proven or probable active TB in patients who underwent kidney transplant between April 1992 and October 2018. For each case, 5 controls were matched by age and sex. Risk factor associated with TB was determined using univariate and multivariate conditional logistic regression. Results Between study period, kidney transplant was performed in 787 patients. None of the recipients was screened or treated for latent tuberculosis. Twenty-seven patients (3.43%) were diagnosed with active TB including 20 proven and 7 probable cases. The overall incidence of TB in our population was 315 cases per 100,000 patients per year. Allograft rejection was significantly associated with active TB (P < 0.001). The median onset of infection was 17 months (IQR, 4–59 months) after transplantation and 3.4 months (IQR, 2.7–16.3 months) after episode of allograft rejection. Majority of patients (96.3%) were cured after complete treatment; however, those with TB remained having significant unfavorable outcomes including higher all-cause mortality and graft loss. Conclusion Incidence of TB in kidney transplant recipients is higher than normal population. Increasing risk of active TB after allograft rejection is probably due to mycobacterial reactivation following high-dose immunosuppression. Since TB is associated with poor post-transplant outcomes, screening, and treatment of latent infection may be beneficial even in endemic country. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Tuberculosis is an important opportunistic infection that affects transplant recipients; the risk of active infection increases significantly when compared with the general population. Most disease results from reactivation of latent infection, being extrapulmonary and disseminated disease the most common presentations. Most cases occur during the first year post-transplantation when immunosuppression is higher. We describe the clinical characteristics of patients diagnosed with TB after transplant. Methods Single-center, retrospective study of adult SOT and HSCT recipients in Mexico City, who developed active TB after transplant. We reviewed medical records, and collected demographic data, clinical characteristics, and outcome. Results We identified 16 patients with post-transplant TB; 13 SOT, and 3 HSCT recipients. The majority of SOT recipients were women (53.8%); median age was 43 years, 9 were kidney and 4 liver transplant recipients. At TB diagnosis, 84.6% of patients were on 3 immunosuppressors. Latent TB was assessed before transplant in 5 patients (38.4%), of these 3 (60%) were tuberculin skin test+, and 2 received isoniazid. Extrapulmonary disease was most common (7, 53.8%). Predominant symptoms were fever (53.8%), chills (30.8%), and diaphoresis (38.5%); six were diagnosed during the 1st year (46.2%) post-transplant; the median of time to diagnosis was 24 months after transplant. The diagnosis was made by histopathology in most cases. Twelve patients received first-line anti-TB treatment. Overall mortality was 30.8%, directly attributable to TB in 2. In the HSCT group, 2 were women; median age was 22 years, 2 allogeneic and 1 autologous transplant. One patient had been treated for latent TB before transplantation. Two developed disseminated disease. Two patients presented within 6 months after the transplant, and the other within a year. Mortality was 100%, attributable to the infection in two patients. Conclusion In regions with intermediate to a high prevalence of TB; post-transplant TB could result from reactivation or post-transplant exposure. Most cases occur within the first year post-transplant; clinical symptoms are nonspecific, which lead to a delay in diagnosis. Morbidity and mortality remains high. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Nocardia species can cause localized or disseminated disease in humans. Infection results from direct inoculation or inhalation. In recent years, several new species have been identified via molecular methods. Further speciation is crucial as each organism has its own spectrum of disease and unique antibiotic susceptibility patterns. Immunosuppression, alcoholism, and certain lung diseases are well-established risk factors for nocardiosis. In fact, cases have incremented in association with increasing population of immunocompromised hosts as well as improved methods for detection and identification. Thus, Nocardia species may be considered opportunistic pathogens. Nocardia bejingensis was first isolated in 2001 by Wang et al from sewage soil in China. The first human infections were reported in Asia. Subsequently, cases were reported in Europe and a few cases have been described in the United States but it has been infrequently cited in the literature. Thus, not much is known about its spectrum of disease. Methods The primary objective of this study was to determine the risk factors and clinical manifestations of Nocardia bejingensis infection via retrospective chart review of 6 cases identified in Tampa General Hospital and Moffitt Cancer Center within a 5-year period. We aimed to evaluate the treatment used and the antibiotic susceptibility patterns of the isolates. Results All patients were immunocompromised (1/3 HIV/AIDS, 1/3 hematologic malignancy, 1/3 solid-organ transplant). Most were male (67%) and mean age of 48. The majority had lung involvement (67%). Thecal sac infection and femur osteomyelitis (OM) were atypical manifestations. Localized disease predominated. Combination therapy was preferred. Trimethoprim-sulfamethoxazole (TMP-SMX), Ceftriaxone, and carbapenems were mostly used. All isolates were susceptible to TMP-SMX. See Table 1. Conclusion This case series depicts clinical features, risk factors, and epidemiology of Nocardia bejingensis infections. Our observations suggest that it is a novel pathogen in the United States, affecting mainly immunocompromised hosts. Early detection, appropriate antibiotics, and surgery were keys in successful management. However, further studies are needed to further elucidate its pathogenesis. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus is a common organism in native septic arthritis. It is traditionally believed to be self-limited with rapid and aggressive debridement and appropriate antibiotic selection. The incidence of S. aureus septic arthritis is increasing, and further characterization is needed to improve diagnosis and treatment. For patients presenting with native S. aureus septic arthritis, we evaluated the reliability of methicillin-resistant S. aureus (MRSA) screening as a predictor to rule out MRSA septic arthritis, the risk factors associated with this disease, and the treatment and surgical outcomes. Methods A retrospective case–control study of patients diagnosed with septic arthritis in the UPMC health system (Pittsburgh, PA) between 2012 and 2016 was completed. The primary outcomes of interest were surgical intervention and the need to alter antibiotic treatment. Patient demographics, characteristics, and outcomes were recorded. Results A total of 215 cases of septic arthritis were identified, and 64% (n = 138) had S. aureu s cultured. In this set, 36% (50/138) of these patients were identified with MRSA. Of the patients diagnosed with MRSA septic arthritis, 50% screened prior to admission had a positive result (8/16) and 48% screened during admission had a positive result (14/29). Compared with septic arthritis with other organisms, risk factors associated with S. aureus included history of intravenous drug use (OR: 4.3, CI: 1.7 to 10.8, P = 0.002) and being immunocompetent (OR: 0.3, CI: 0.1 to 0.6, P = 0.002). These infections were associated with concurrent infections of the spine (OR: 5.7, CI: 2.1 to 15.1, P = 0.0005). As compared with other organisms, there was a high probability of switching antibiotics during treatment (OR: 3.7, CI: 1.1 to 13.0, P = 0.04) and relapse of infection (OR: 4.2, CI: 1.2 to 14.6, P = 0.02). Conclusion S. aureus septic arthritis is associated with intravenous drug use, and not with immunosuppression. A negative MRSA screen does not rule out this organism. Concurrent spine infections are common. There is a high likelihood of infection relapse and that antibiotics will need to be altered during treatment. With the opioid epidemic, the incidence is likely to increase further. More work is needed to improve diagnosis and overcome treatment challenges. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Candidemia is a common cause of healthcare-associated bloodstream infection with high mortality rates despite antifungal therapy. Risk factors include prolonged ICU stay, immunosuppression, and exposure to broad-spectrum antibiotics. Blood cultures (BC) remain the gold standard for diagnosis but lack sensitivity and can take days to result. T2Candida (T2C) is a rapid diagnostic test utilizing PCR and magnetic resonance technology to detect five Candida species in whole blood in less than 6 hours. In this study we examined characteristics of patients with positive T2C assays in the absence of positive BC including risk factors and 30-day mortality rates. Methods We conducted a retrospective analysis of positive T2C cases at UAB Medical Center from 2016 to 2018 with either negative or no BC. For each patient we determined if clinical signs (e.g. hypotension, leukocytosis) and risk factors for candidemia were present at the time of collection. Our primary outcome of interest was 30-day mortality. Data were compared by multivariate analysis. Results A total of 173 patients with T2C positivity alone were included in the analysis. The most common risk factor was the use of broad-spectrum antibiotics followed by CVC (Table 1). The mean number of risk factors per patient was 3.6 (Figure 1). Overall 30-day mortality was 41%. Patients with a T2C result of C. albicans / C. tropicalis were almost 2.5 times more likely to die at 30 days (aOR 2.401, CI 1.159–4.974) compared with those with other positive results. Increasing number of risk factors (aOR 1.457, CI 1.126–1.886) and increasing age (aOR 1.052, CI 1.026–1.079) were significantly associated with increased odds of death at 30 days (Table 2). Conclusion In this study we demonstrate a significant association between increasing number of risk factors, older age, and A/T result with higher odds of 30-day mortality among patients with T2C positivity alone. While concern for false-positives exists when using T2C, our data suggest that this is an acutely ill population which warrants early and aggressive antifungal therapy. The lower limit of detection of T2C (1 cfu/mL) as compared with BC may explain lack of paired positive cultures in these patients despite clinical signs of and risk factors for candidemia. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Due to severe immunosuppression, patients undergoing allogeneic hematopoietic stem cell transplantation (aSCT) are at increased risk of infection and especially bloodstream infections (BSI) remain a major cause of death. Knowledge of the specific epidemiology of pathogens and resistances is of utmost importance to optimize antimicrobial treatment strategies. Methods Based on the Cologne Cohort of Neutropenic Patients (CoCoNut) database, we conducted a retrospective analysis of blood cultures collected within 100 days following transplantation of patients undergoing aSCT between January 2009 and December 2018 at the University Hospital of Cologne, Germany. Contamination of coagulase-negative Staphylococci (CoNS) isolates (single positive isolate within 5 days) was considered within the analysis. Results In total, 843 aSCT patients were available for analysis (484/843 [57%] male). The median age was 53 (interquartile range [IQR] 43–62) years, predominant underlying diseases were acute myeloid leukemia (47%, 397/843), lymphoma (14%, 117/843), and acute lymphoblastic leukemia (11%, 89/843). Median inpatient stay was 39 (IQR 34–50) days, while 67/843 (8%) patients died. Antibacterial prophylaxis was administered in 289/843 (34%) and antifungal prophylaxis in 738/843 (88%) patients. BSI was diagnosed in 233/843 (28%) patients. In total, 5,489 pairs of blood cultures were taken (median 4 per patient, IQR 2–8), while a pathogen could only be detected in 922/5,489 (17%). Most frequent pathogens were CoNS (259/922, 28%), Enterococcus spp. (219/922, 24%), E. coli (132/922, 14%), Klebsiella spp. (44/922, 5%), P. aeruginosa (39/922, 4%), S. aureus (37/922, 4%), and Candida spp. (42/922, 5%). Polymicrobial infection was detected in 58/922 (6%) cases. Within Enterococci isolates, 24/219 (11%) were VRE. None of the Klebsiella , but 9/132 (7%) of E. coli isolates were ESBL positive. In 4/37 (11%) cases S. aureus isolates were MRSA. Conclusion Patients in the early phase after aSCT are at high risk of BSI with a predominantly gram-positive spectrum. Empirical antimicrobial treatment must consider pathogen epidemiology and resistance patterns while waiting for blood culture results. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background HSCT patients are at an increased risk of developing PJP after transplant due to treatment induced immunosuppression. Given the risk of cytopenias with co-trimoxazole, AP is utilized as an alternative for PJP prophylaxis. A prior study revealed a 0% (0/19 patients) incidence when AP prophylaxis was given for one year post autologous HSCT. Current guidelines recommend a duration of 3 – 6 months for PJP prophylaxis in autologous HSCT. The primary endpoint of this study was to assess the incidence of PJP infection within one year post autologous HSCT in patients who received 3 months of AP. Secondary endpoint was a cost comparison of 3 months compared with 6 months of AP. Methods A single-center, retrospective study of adult autologous HSCT patients at Yale New Haven Hospital between February 2013 and December 2017 was performed. Patients were excluded if: <18 years of age, received < or >3 months of AP, changed to alternative PJP prophylactic agent or received no PJP prophylaxis, received tandem HSCT, deceased prior to one year post-transplant from a non PJP-related infection, HIV positive, or lost to follow-up. Pentamidine was given as a 300 mg inhalation monthly for 3 months starting Day +15 after autologous HSCT. Results A total of 288 patients were analyzed, no PJP infections occurred within one year post HSCT. Additionally, 187 (65%) patients received treatment post HSCT with 135/215 (63%) receiving maintenance immunomodulatory drugs for myeloma and 40/288 (14%) patients developing relapsed disease. 43% of the chemotherapy regimens for relapsed disease included high dose corticosteroids. The cost difference of using 3 months vs. 6 months of AP is $790, reflecting the cost of drug and its administration. Applying our incidence of 0%, potential cost savings of 3 months vs. 6 months of AP would be $330,000 over 5 years or $66,000 per year. Conclusion Three months of AP for PJP prophylaxis in autologous HSCT patients is safe and effective as well as cost-effective compared with a 6 month regimen. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Fluoroquinolone (FQ) prophylaxis for high-risk neutropenic patients has been shown to reduce rates of febrile neutropenia and is standard at many centers. For patients who cannot receive a FQ, oral third-generation cephalosporins (OTGCs) are often used as an alternative; however, this strategy is not well studied. We sought to compare clinically-relevant outcomes in patients receiving FQ vs. OTGC prophylaxis. Methods This was a retrospective cohort study of adults who were admitted to the Malignant Hematology service at the University of California, San Francisco between December 2012 and June 2018 and received >48 hours of an OTGC (cefdinir or cefpodoxime) or an FQ (levofloxacin) for neutropenic prophylaxis. For each OTGC patient, an FQ patient was randomly selected from the same admission year. Exclusion criteria were fever on admission, receipt of systemic antibiotics prior to or during the prophylaxis period, diagnosis of acute promyelocytic leukemia, and crossover. A multivariable logistic regression analysis adjusting for age, QTc, Charlson Comorbidity Index, underlying diagnosis, receipt of stem cell transplant (SCT), and duration of neutropenia was used to compare the groups with respect to a primary composite outcome of 30-day in-hospital mortality, intensive care unit (ICU) admission, and bacteremia. Results Of 520 patients screened, 173 (33.3%) were included in the study; 76 of these received an OTGC and 97 received an FQ. Hematologic diagnoses included multiple myeloma (38.2%), acute myeloid leukemia (29.5%), acute lymphoblastic leukemia (8.7%), B-cell lymphoma (12.7%), aplastic anemia (2.9%), and others (3.5%). During admission, 9.2% underwent allogeneic SCT and 28.3% underwent autologous SCT. Outcomes are shown in Table 1. Conclusion Prophylaxis with an OTGC rather than a FQ was not associated with worse outcomes in this pragmatic evaluation of a heterogeneous group of patients with hematologic malignancies. In this multivariable model, neutropenia lasting more than 7 days was the only consistent predictor of failure across outcomes, suggesting that degree of immunosuppression is a much more significant driver of poor outcomes in this population than is prophylaxis choice. Further evaluation of the role of prophylaxis is needed. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Clostridium difficile infection (CDI) is a known major financial burden. In the cancer population, CDI, was identified to have a peak incidence of 17.2 per 1000 patients with increased morbidity, mortality and hospital length of stay. The need to further elucidate chemotherapy (CTX) with vs. without ABX usage as risk factors among other variables in cancer patients arises since this population is already baseline immunocompromised. Methods A retrospective case–control study (total of 1989 cancer patients who received CTX and had diarrhea at UTMB through 1/2016–1/2018) was completed. Subjects were screened using extensive inclusion and exclusion criteria, and assigned as CASES (with symptomatic (s) diarrhea from proven CDI) and as CONTROLS (had diarrhea but not attributed to CDI). A 1:1 subject matching using age, sex and past medical histories was completed and a total of 46 patients: 23 cases and 23 controls were compared and analyzed. McNemar's and independent t test of equal variance were used for association and comparing means/medians, respectively. Two-sided P value ≤ 0.05 was considered significant. Results The use of ABX (OR = 16, P = 0.0007) and having any degree of neutropenia at the time of diarrhea (OR = 12, P = 0.0055) among CTX patients had significant associations with having s CDI. Although no significant association between sCDI and # of days post CTX exposure (≥7 days (P = 0.1138) and ≥14 days post CTX (P = 0.1489) was identified, a mean of 12.83 ± 7.69 days passed before sCDI diagnosis in cases, compared with diarrhea diagnosis (7.46 ± 6.1 days) in controls (P = 0.0119). Meanwhile, receiving >1 CTX cycle (P = 1.000) and particular CTX types (P = ~ 0.0771–1.000) had no significant associations with sCDI diagnosis. Conclusion Any ABX usage post CTX exposure heavily predisposes to s CDI among cancer patients likely due to elimination of gut flora on an already predisposed population. Having any degree of neutropenia was also associated with having s CDI likely due to significant immunosuppression on top of being baseline cancer patients receiving CTX, and may have predictability benefits. The other variables may have not been significant due to expected limited cases because of low CDI incidence. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background In January 2019, the Clinical and Laboratory Standards Institute (CLSI) lowered breakpoints of fluoroquinolones (FQ) for Enterobacteriaceae (EB)and Pseudomonas aeruginosa (PsAr). Automated commercial antimicrobial susceptibility testing (cAST) can only report levofloxacin MIC ≤1 μg/mL according to 2018 breakpoints. Updated panels will not be available until FDA approval. Laboratories and antimicrobial stewardship programs (ASP) must decide how to implement the adoption of new FQ breakpoints. Methods All microbiologic isolates of EB or PsAr were collected March 11, 2019–March 22, 2019. Manual E-tests and cAST by Microscan were performed for levofloxacin. Susceptible or non-susceptible (NS) isolates to levofloxacin were identified using 2018 and 2019 CLSI breakpoints [Table1]. Data were analyzed by Microsoft Excel and SPSS. Results 159 isolates were analyzed. Isolates were predominantly from urine (78%) and females (68%). E.coli was the most frequently identified organism (40%) [Figure 1]. Application of new breakpoints changed 7% of EB (P = 0.083) and 16% of PsAr (P = 0.238) from susceptible to NS. [Figure 2] PsAr had higher rates of FQ NS compared with EB with new breakpoints (37% vs. 22%, P = 0.132, not shown). Non-urine and inpatient isolates had decreased susceptibility of ≥10% (P = 0.168 and 0.117). Lack of other resistance mechanism (ESBL, CRE, MDRO) was associated with a change in susceptibility (P = 0.036). Diagnosis of active cancer or immunosuppression (IS) was strongly associated with FQ NS by new breakpoints (P = 0.019, not shown). Patients with cancer or IS had the largest decrease in susceptibility (18%, P = 0.069) with application of new breakpoints. [Table 2]. Conclusion Updated CLSI FQ breakpoints resulted in trends of increased resistance. PsAr, non-urine and inpatient isolates were disproportionately affected. Implementation of manual MIC determination from select clinical isolates may be useful until approval of updated cAST. Diagnosis of cancer or IS was associated with FQ NS by new breakpoints. Restriction of FQ for empiric use may be considered, particularly in patients with cancer or IS. Larger studies are needed to determine the long-term effects of adjusted FQ breakpoints, but are anticipated to have significant impacts on ASP. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab  10  Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months)  7  Number of patients on rituximab monotherapy  2  Number of patients who are 6 months post-treatment  1  Number of patients with other risk factors for PCP  1 (hypogammaglobulinaemia)  Number of patients who are eligible for prophylaxis, as per the guideline  8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia)  Number of patients on cotrimoxazole  7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole  Total number of patients who had rituximab  10  Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months)  7  Number of patients on rituximab monotherapy  2  Number of patients who are 6 months post-treatment  1  Number of patients with other risk factors for PCP  1 (hypogammaglobulinaemia)  Number of patients who are eligible for prophylaxis, as per the guideline  8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia)  Number of patients on cotrimoxazole  7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole  P54 Table 1 Total number of patients who had rituximab  10  Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months)  7  Number of patients on rituximab monotherapy  2  Number of patients who are 6 months post-treatment  1  Number of patients with other risk factors for PCP  1 (hypogammaglobulinaemia)  Number of patients who are eligible for prophylaxis, as per the guideline  8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia)  Number of patients on cotrimoxazole  7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole  Total number of patients who had rituximab  10  Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months)  7  Number of patients on rituximab monotherapy  2  Number of patients who are 6 months post-treatment  1  Number of patients with other risk factors for PCP  1 (hypogammaglobulinaemia)  Number of patients who are eligible for prophylaxis, as per the guideline  8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia)  Number of patients on cotrimoxazole  7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole  We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) are rare small and medium vessel vasculitides that include granulomatosis polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). This retrospective review summarises the clinical features of a cohort of patients with childhood onset AAV at a single tertiary centre in the North West of England. Methods Identification of all patients with diagnosis of ANCA-associated vasculitis diagnosed from 2014 to 2019, using department database and PEDVAS data. Clinical information was collected retrospectively using electronic patient record and case notes. Results 10 patients with AAV were identified, with GPA being the most common diagnosis (7 patients). 2 patients had MPA and 1 had EGPA. All patients with GPA fulfilled consensus EULAR/PRES criteria. The EGPA patient fulfilled ACR classification criteria.1 MPA patient fulfilled Chapel Hill Consensus Conference criteria. MPA presented in a younger age group compared to EGPA. AAV was more common in females, 8:2 female to male ratio, Table 1. All patients had pulmonary and renal involvement, with the exception of one EGPA patient having pulmonary disease with no evidence of glomerulonephritis (GN). MPA patients had significant renal disease and presented early, within 1 month of clinical symptoms. GPA patients had an average duration of symptoms of 2.5 months before presentation. GPA patients were mainly cANCA PR3 positive and MPA patients were MPO positive. The EGPA patient was not ANCA positive but had histological diagnosis of granulomatous vasculitis. 3 patients with GPA underwent plasmapheresis, with evidence of proliferative GN and pulmonary disease at presentation. One of these patients sustained pulmonary haemorrhage. The 2 patients with MPA presented with significant renal failure; one patient died 19 months after diagnosis, the other had renal transplant. All patients received cyclophosphamide and required further immunosuppression with either DMARD or biologic. Most patients remain on MMF or rituximab as maintenance therapy which appears successful in maintaining remission so far. P31 Table 1: Demographics and clinical features of patients with AAV   GPA, n = 7  MPA, n = 2  EGPA, n = 1  Gender F:M  6:1  2:0  0:1  Mean age at onset  13.2 (8.7- 15)  5.9 (2.3- 9.6)  11.8  (years)  Mean duration of follow-up (months)  23.2 (5- 36)  28.5 (19- 38)  53  Mean duration of symptoms  2.5 (1-6)  1 (1)  11  pre-presentation (months)  ENT  4  1  1  Pulmonary  7  2  1  Renal  7  2  0  Asthma  0  0  1  Eosinophilia  0  0  1  ANCA PR3 +ve  6  0  0  ANCA MPO +ve  1  2  0  ESRF  0  2  0  Death  0  1  0  Plasmapheresis  3  2  0  Cyclophosphamide  7  2  1  Azathioprine  3  1  1  MMF  3  2  1  Rituximab  4  1  1    GPA, n = 7  MPA, n = 2  EGPA, n = 1  Gender F:M  6:1  2:0  0:1  Mean age at onset  13.2 (8.7- 15)  5.9 (2.3- 9.6)  11.8  (years)  Mean duration of follow-up (months)  23.2 (5- 36)  28.5 (19- 38)  53  Mean duration of symptoms  2.5 (1-6)  1 (1)  11  pre-presentation (months)  ENT  4  1  1  Pulmonary  7  2  1  Renal  7  2  0  Asthma  0  0  1  Eosinophilia  0  0  1  ANCA PR3 +ve  6  0  0  ANCA MPO +ve  1  2  0  ESRF  0  2  0  Death  0  1  0  Plasmapheresis  3  2  0  Cyclophosphamide  7  2  1  Azathioprine  3  1  1  MMF  3  2  1  Rituximab  4  1  1  P31 Table 1: Demographics and clinical features of patients with AAV   GPA, n = 7  MPA, n = 2  EGPA, n = 1  Gender F:M  6:1  2:0  0:1  Mean age at onset  13.2 (8.7- 15)  5.9 (2.3- 9.6)  11.8  (years)  Mean duration of follow-up (months)  23.2 (5- 36)  28.5 (19- 38)  53  Mean duration of symptoms  2.5 (1-6)  1 (1)  11  pre-presentation (months)  ENT  4  1  1  Pulmonary  7  2  1  Renal  7  2  0  Asthma  0  0  1  Eosinophilia  0  0  1  ANCA PR3 +ve  6  0  0  ANCA MPO +ve  1  2  0  ESRF  0  2  0  Death  0  1  0  Plasmapheresis  3  2  0  Cyclophosphamide  7  2  1  Azathioprine  3  1  1  MMF  3  2  1  Rituximab  4  1  1    GPA, n = 7  MPA, n = 2  EGPA, n = 1  Gender F:M  6:1  2:0  0:1  Mean age at onset  13.2 (8.7- 15)  5.9 (2.3- 9.6)  11.8  (years)  Mean duration of follow-up (months)  23.2 (5- 36)  28.5 (19- 38)  53  Mean duration of symptoms  2.5 (1-6)  1 (1)  11  pre-presentation (months)  ENT  4  1  1  Pulmonary  7  2  1  Renal  7  2  0  Asthma  0  0  1  Eosinophilia  0  0  1  ANCA PR3 +ve  6  0  0  ANCA MPO +ve  1  2  0  ESRF  0  2  0  Death  0  1  0  Plasmapheresis  3  2  0  Cyclophosphamide  7  2  1  Azathioprine  3  1  1  MMF  3  2  1  Rituximab  4  1  1  Conclusion Childhood onset AAV are severe diseases with significant morbidity and mortality. Rituximab was found to be effective in induction as well as maintenance therapy in our patients. In our cohort, children had multi-system involvement at presentation. Clinicians should investigate thoroughly for ENT, pulmonary and renal complications at diagnosis. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background From our experience, a small cohort of patients with juvenile idiopathic arthritis (JIA) develop irreversible damage to ankle and subtalar joints despite immunosuppression with methotrexate and multiple biologic agents. In this case series, we describe 4 patients with JIA and erosive damage to ankle or subtalar joints who underwent arthrodesis by a single surgeon between 2011-2017 due to longstanding pain and impaired function despite medical and orthotic interventions. We assessed patient satisfaction regarding the procedure in terms of pain and function. There are no previous case series describing arthrodesis of ankle and subtalar joints in JIA. A case series of 8 patients with severe tibiotalar JIA who had arthrodiastasis (joint distraction) reported an improvement in pain and functional scores. Methods In this retrospective case series we reviewed the records of 4 paediatric patients with JIA in Scotland who underwent ankle arthrodesis performed by a single orthopaedic surgeon between 2011 and 2017. Questionnaires were posted out to each patient. These included Manchester-Oxford Foot scores (MOxFQ) and EQ5D scores. Results Time from diagnosis to commencing methotrexate (MTX) was 22 (6-30) months, time from diagnosis to biologic therapy was 5 (2-8) years and time to arthrodesis was 10 (6-14) years (Table 1). Age at surgery was 16 (13-20) years. Prior to surgery all patients reported significant ankle pain and 2 patients needed to wear an ankle-foot orthosis (AFO). Radiological features before surgery in these patients included marked degenerative changes and loss of articular cartilage in the ankle joints on MRI. All patients reported favourable scores in terms of function and pain following ankle or subtalar arthrodesis. Two patients expressed that they wished they had undergone surgery sooner. P12 Table 1: Patient Characteristics Patient  JIA Subtype  Comorbidity  Age at diagnosis of JIA (years)  Systemic Therapy  No of joint injection episodes  Visual Analogue Pain Score Post-Surgery  1  RF –ve Polyarticular  Nil  8  MTX  3    Etanercept  Adalimumab  Abatacept  2  Extended oligoarticular  Uveitis  3  MTX  4  1/10  Adalimumab  3  RF –ve Polyarticular  Nil  6  MTX  4  0/10  Etanercept  4  RF –ve Polyarticular  Trisomy 21, VSD closure, obstructive sleep apnoea  11  MTX  7    Etanercept  Tocilizumab  Patient  JIA Subtype  Comorbidity  Age at diagnosis of JIA (years)  Systemic Therapy  No of joint injection episodes  Visual Analogue Pain Score Post-Surgery  1  RF –ve Polyarticular  Nil  8  MTX  3    Etanercept  Adalimumab  Abatacept  2  Extended oligoarticular  Uveitis  3  MTX  4  1/10  Adalimumab  3  RF –ve Polyarticular  Nil  6  MTX  4  0/10  Etanercept  4  RF –ve Polyarticular  Trisomy 21, VSD closure, obstructive sleep apnoea  11  MTX  7    Etanercept  Tocilizumab  P12 Table 1: Patient Characteristics Patient  JIA Subtype  Comorbidity  Age at diagnosis of JIA (years)  Systemic Therapy  No of joint injection episodes  Visual Analogue Pain Score Post-Surgery  1  RF –ve Polyarticular  Nil  8  MTX  3    Etanercept  Adalimumab  Abatacept  2  Extended oligoarticular  Uveitis  3  MTX  4  1/10  Adalimumab  3  RF –ve Polyarticular  Nil  6  MTX  4  0/10  Etanercept  4  RF –ve Polyarticular  Trisomy 21, VSD closure, obstructive sleep apnoea  11  MTX  7    Etanercept  Tocilizumab  Patient  JIA Subtype  Comorbidity  Age at diagnosis of JIA (years)  Systemic Therapy  No of joint injection episodes  Visual Analogue Pain Score Post-Surgery  1  RF –ve Polyarticular  Nil  8  MTX  3    Etanercept  Adalimumab  Abatacept  2  Extended oligoarticular  Uveitis  3  MTX  4  1/10  Adalimumab  3  RF –ve Polyarticular  Nil  6  MTX  4  0/10  Etanercept  4  RF –ve Polyarticular  Trisomy 21, VSD closure, obstructive sleep apnoea  11  MTX  7    Etanercept  Tocilizumab  Conclusion This case series helps demonstrate patient satisfaction in the small group of patients in our service where irreversible erosive disease caused pain and dysfunction not responsive to medical therapy. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Juvenile osteochondritis dissecans (JOCD) is a condition of bone and cartilage lesions. Contributory factors may include ischaemia, trauma, genetic or biomechanical factors such as abnormal joint loading. Children and young people (CYP) with juvenile idiopathic arthritis (JIA) have low physical activity levels, present with joint abnormalities and are exposed to immunosuppression including steroids which may cause reduced bone density. Here we describe JOCD in CYP with JIA in our service. Methods Retrospective reviews of case notes were conducted for current CYP with JIA in our service with known JOCD, detailing: JIA diagnosis Age & BMI at diagnosis Symptom duration pre-diagnosis Management (including steroids) JOCD diagnosis Age & BMI at diagnosis Imaging Management Results Table 1 summarises the results. Twelve (n = 10 female) CYP in our cohort of 270 had JOCD with 20 lesions diagnosed on magnetic resonance imaging (MRI). Polyarticular (n = 4) and extended oligoarticular (n = 5) were the commonest JIA sub-types with all CYP receiving systemic therapy and 75% (n = 9) requiring more than one biologic. Mean symptom duration before JIA diagnosis was 6 months (range: 1-24 months) with a mean age of 6.5 years (range: 1.5-13 years). Mean time to JOCD diagnosis was 5.5 years (range: 1.5-10.25 years) with a mean age of 12 years (range: 8-17 years) and 7 CYP having a high BMI (>85th percentile for age). The mean number of previous steroid injections per JOCD joint was 4 (range: 0-17) compared with 3 (range: 0-8) in the non-JOCD joint. Talar dome lesions (n = 9) were commonest, followed by femoral condyle (n = 4 medial, n = 3 lateral). Initial management was conservative, with half (n = 10) requiring surgery. P09 Table 1     P09 Table 1     Conclusion This review identifies that 4% (n = 12/270) of our CYP with JIA have known JOCD, compared with 0.03% (n = 29/100,000) of the general population. Risk factors appear to be polyarticular disease, exposure to ≥ 4 steroid injections per joint, biologic-resistant disease and high BMI with low physical activity. Where CYP with JIA report symptoms which do not fit an inflammatory pattern there should be a low threshold to consider JOCD, with prospective research needed to better understand the relationship between JOCD and JIA. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Highlights from the article: Poroid neoplasms encompass several sub-types of tumors: por- The patient was evaluated for a scalp lesion. Immunocompromised host, scalp, therapeutic immunosuppression, natural immunosuppression, neoplasms, eccrine acrospiroma, head and neck, excision, scalp nodules.

Laryngeal post-transplant lymphoproliferative disease (PTLD) is rare. Here, we describe two pediatric cases. The first, a 15-month-old who underwent liver transplantation at 5 weeks, presented with airway distress. Airway evaluation identified epiglottic and arytenoid infiltrate, and biopsy was consistent with polymorphic PTLD. The second, a 23-month-old who underwent liver transplantation at 13 months, presented with progressive stridor. Airway evaluation revealed sub-mucosal infiltrate of the epiglottis, arytenoids, post-cricoid region, and uvula. Biopsy was consistent with monomorphic PTLD. Airway findings and symptoms resolved for both after immunosuppression reduction. PTLD diagnosis requires a high index of suspicion in post-transplant patients with airway obstruction. [ABSTRACT FROM AUTHOR]

Splenic rupture in the absence of major trauma is a rare occurrence, which may occur by idiopathic means or a specific pathologic process. One such condition, amyloidosis, involves the extracellular deposition of abnormally folded 'amyloid' protein, which can affect the spleen. Protein infiltration in the organ may cause splenomegaly and potentially capsular rupture in advanced cases. We describe a 68-year-old male with a history of end-stage renal disease status-post living donor renal transplant on chronic immunosuppression and Coumadin that presented with abdominal pain, weakness and hypotension. The patient was found to have hemoperitoneum secondary to splenic rupture and was emergently taken for exploratory laparotomy and splenectomy. The pathology of the spleen revealed AL amyloidosis. He was subsequently found to have advanced plasma cell neoplasm by bone marrow biopsy with numerous osseous lytic lesions, consistent with a monomorphic post-transplant lymphoproliferative disorder. [ABSTRACT FROM AUTHOR]

Pituitary adenomas are commonly benign neoplasms which may manifest with a wide variety of symptomatology. Typically, ACTH- producing tumors of the pituitary gland present with central fat deposition, abdominal striae, moon facies, buffalo hump, osteoporosis, hypertension, hirsutism, gonadal dysfunction, immunosuppression, and less commonly with hyperglycemia due to insulin resistance. We report the case of a 58-year-old male patient with an ACTH producing pituitary microadenoma and type 2 Diabetes Mellitus (DM) whose primary presenting symptom was increasing insulin resistance despite appropriate adjustments to his insulin therapy. Bilateral inferior petrosal sinus sampling showed results highly suspicious for a left sided pituitary microadenoma. Endoscopic endonasal transsphenoidal resection of the pituitary tumor was performed to resect the microadenoma of the left gland. This case adds to the diverse presentations of pituitary adenomas, in that these lesions must be included in the differential diagnosis of a type 2 DM patient with hyperglycemia and insulin resistance. [ABSTRACT FROM AUTHOR]