bluuebunny/crossref_metadata_2025_split huggingface dataset:
2674. Microbiome and Cumulative Antibiotic Use as Predictors of Stenotrophomonas maltophilia Infection in Patients with Acute Myeloid Leukemia Receiving Remission-Induction Chemotherapy
Authors: Aitken Samuel L , Aitken Samuel L , Shelburne Samuel A , Shelburne Samuel A , Galloway-Peña Jessica 
Published: October 2019

Abstract

Background
S. maltophilia infections are increasingly common in patients with acute myeloid leukemia (AML) and associated with high mortality. S. maltophilia is a frequent colonizer in AML patients but relatively little is known about factors that drive S. maltophilia infection. We sought to evaluate the utility of cumulative antibiotic use and the microbiome as predictors of S. maltophilia infection in AML patients receiving remission induction chemotherapy (RIC).

Methods
We performed a subanalysis of a prospective, observational cohort study between September 2013 and August 2015 of adult patients with AML receiving RIC. In this study, fecal and oral microbiome samples collected every 96 hours from the start of RIC until neutrophil recovery were assessed for the relative abundance of S. maltophilia via 16s rRNA quantitation. The primary outcome, microbiologically proven S. maltophilia infection, was analyzed using a time-varying Cox proportional hazards model accounting for S. maltophilia relative abundance and cumulative antibiotic exposure. Patients were censored at neutrophil recovery or death.

Results
90 patient were included; of whom, 8 (9%) developed S. maltophilia infection (pneumonia, n = 6; skin/soft-tissue infection, n = 2). 4/8 (50%) patients were bacteremic. 7/8 (88%) patients with S. maltophilia infection had detectable oral 16s oral reads mapping to S. maltophilia vs 22/82 (27%) without infection (P < 0.01). An oral S. maltophilia relative abundance of 36% predicted infection (sensitivity: 96%, specificity 93%, likelihood ratio +: 17.08). No association of S. maltophilia infection with the fecal relative abundance was seen. Cumulative meropenem exposure was associated with increased infection risk (hazard ratio [HR] 1.17, 95% CI 1.01 – 1.35, P = 0.03), while levofloxacin was associated with decreased infection risk (HR 0.83, 95% CI 0.66 – 1.04, P = 0.10).

Conclusion
The oral microbiome may play an important role in S. maltophilia pathogenesis in AML patients. Cumulative antibiotic exposure likely modifies S. maltophilia infection risk. These data suggest that real-time molecular monitoring of the oral cavity for S. maltophilia in AML patients could identify patients at high risk for S. maltophilia infection and improve targeted therapy.

Disclosures
Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.
2684. The Prospective Pilot Study of Infectious Complication Surveillance in Active Systemic Lupus Erythematosus Patients with Intense Immunosuppressive Therapy: Cellular Response and Clinical Outcomes
Authors: Rotjanapan Porpon , Kirdlarp Supachok , Suangtamai Tanitta , Bruminhent Jackrapong , Ngamjanyaporn Pintip , Pisitkun Prapaporn 
Published: October 2019

Abstract

Background
Despite a common complication, the real interplays between the infectious sequelae and systemic lupus erythematosus (SLE) with intense immunosuppressive therapy (IT) are not fully understood.

Objective
To identify the cellular biomarkers that justify the risk for overall infection in active SLE patients with intense IT.

Methods
An observational, prospective cohort pilot study was conducted in active SLE patients with intense IT aged >15 years from November 2017 March 2019 at Ramathibodi Hospital, Bangkok, Thailand. Clinical data and T-cell subpopulation analyses, at weeks 0 (at enrollment), 2, 4, 8, and 16 were obtained. Every patient was monitored over a 24-week period. The infections of interest were any emerging infections other than cytomegalovirus infection (CMV). Intense IT was defined as an induction therapy of active SLE disease with either the National Institute of Health or Euro-Lupus Nephritis Trial protocol regimens.

Results
A total of 23 active SLE patients were enrolled, 91.3% were female with the median age (interquartile range, IQR) of 27.7 (23.0–42.1) years old. The median SLE disease activity index (IQR) was 16 (10–20) and 73.9% had renal abnormality. At week 12, the prevalence of infection was 39.1% being bacterial infection in 77.8% and viral infection in 22.2%. There was no mortality in this study. Non-infection group had higher proportions of absolute lymphocyte count (ALC), CD3+ T cell, and CD3+CD56+ natural killer T (NKT) cell numbers compared with the infection group; [median of 1169.8 (694.4–1921.4) vs 716.1 (429.0–882.0) cells/µL; P = 0.044, 585.1 (245.1–669.2) vs. 204.9 (73.9–286.5) cells/µL; P = 0.017, and 50.5 (13.7–152.2) vs. 4.35 (2.44–52.9) cells/µL, P = 0.040, respectively]. Patients with NKT cells >9.31 cells/µL had longer median infection-free day of 25.3 days (19.7–25.3) vs. 2.0 days (1.7–4.0) in patients with lower NKT cell count (log rank P < 0.001). The Cox-proportional hazard ratio was 0.03, P = 0.003 (95% confidence interval 0.004–0.300).

Conclusion
Bacterial infections are common in active SLE patients with intense IT. Monitoring of ALC, CD3+ T-cell, and NKT-cell counts can potentially be used as the infectious risk prognosticators. However, a study in a larger scale is encouraged to verify these findings.

Disclosures
All authors: No reported disclosures.
2685. Oral Third-Generation Cephalosporins vs. Levofloxacin for Antibacterial Prophylaxis in Neutropenic Patients with Hematologic Malignancies
Authors: DeVoe Catherine , Trinh Trang D , Moises Joshua , Pham Binh C , Tran Allen V , Vuong Lisa , Doernberg Sarah B 
Published: October 2019

Abstract

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.
2690. Infectious Complications in Adult Leukemic Patients with Prolonged Neutropenia Undergoing Induction Chemotherapy
Authors: Sabapathy Vidhya , Klinkova Olga , Balbona Joseph , Greene John 
Published: October 2019

Abstract

Background
Induction chemotherapy in patients with the diagnosis of acute leukemia is associated with a high incidence of infectious complications. While prior studies provide information regarding infectious complications in this patient population, more research is needed to evaluate infection complications in a subgroup of leukemic patients with prolonged neutropenia who often require repeat induction chemotherapy.

Methods
This was a retrospective analysis of 61 patients ages 18–85, between January 1, 2010 and March 14, 2018 who were diagnosed and being treated for acute leukemia. All selected patients experienced severe neutropenia (defined as absolute neutrophil count <500/μL) for ≥7 days. 33 patients underwent their first induction chemotherapy while 28 patients underwent repeat induction chemotherapy. Patient characteristics and infectious complications were examined. Analysis was performed to further study blood stream infections in this patient population.

Results
Sixty-one patients, mean age of 55 ± 17, were included in this study. Acute myelogenous leukemia was the most common diagnosis (n = 47, 77%). The average duration of neutropenia in single vs multiple induction group was 40 vs. 47.2 days (P = 0.38), respectively. 198 culture-proven infections were identified. Overall, bloodstream infections were the most common site (n = 78, 39.4%), followed by respiratory tract infections (n = 39, 19.7%). Gram-positive organisms were the leading etiology of bacteremias (n = 50, 64%). Bacteremia episodes were more common in the patients undergoing multiple induction chemotherapy comparing to a single treatment (45 vs. 33 episodes). Patients undergoing multiple induction chemotherapy experienced a higher rate of Gram-negative blood stream infection episodes comparing to a single induction group (n = 18/78, 23.1% vs. n = 10/78, 12.8%).

Conclusion
Overall, bacteremia was the most common infection in this patient population, followed by respiratory tract infections. Gram-positive pathogens were the most common etiology of bacteremia when all patients were analyzed. However, in the subset of patients undergoing multiple induction chemotherapy, Gram-negative pathogens were the leading cause of the blood-stream infections.

Disclosures
All authors: No reported disclosures.
2691. Comparison of Incidence and Mortality of Kaposi’s Sarcoma Amongst Solid-Organ Transplant Recipients
Authors: Gummadi Padma Priya , Aurit Sarah , Destache Christopher J , Walters Ryan , George Elizabeth K , Vivekanandan Renuga , Velagapudi Manasa 
Published: October 2019

Abstract

Background
Kaposi’s sarcoma (KS) is a lymphatic endothelium-derived tumor caused by Human Herpes Virus 8 (HHV-8). Organ transplant recipients are at increased risk of this malignancy due to use of immunosuppressive therapy. In this observational trial, the incidence of KS in different organ transplant recipients as well as mortality were investigated.

Methods
Patient information was retrieved from the United Network for Organ Sharing (UNOS) database to identify all liver, kidney, heart, or lung transplant recipients, and those who were subsequently diagnosed with KS. Patients were stratified by transplant organ, clinical and demographic information was obtained to characterize each population. Unadjusted differences in incidence, mortality, and patient characteristics were examined with chi-square or Fisher exact test for categorical variables; continuous variables were examined with the Kruskal–Wallis test which was Bonferroni adjusted for multiple comparisons. Patients < 18 years of age, who had missing information concerning the development of a Kaposi’s sarcoma, or who underwent multiple organ transplant were excluded. SAS, v. 9.4, was used for statistical analysis; P < 0.05 was considered significant.

Results
Patient demographics are described in Table 1. The development of KS was significantly different among organ transplant types. Kidney transplant recipients had a higher incidence of KS in comparison to liver transplant recipients (P < 0.001). Mortality was the highest in lung transplant recipients who developed KS, which was significantly higher than kidney (P < 0.001) or liver transplant recipients (P = 0.005). Finally, it was determined that there was a significant difference in age and race (white vs. non-white) among the various organ transplants (P < 0.001, respectively)

Conclusion
Although incidence of KS is significantly higher post renal transplant, mortality is highest in lung transplant recipients. Further investigation is needed to understand differences in mortality among transplant recipients. This will help identify at risk subjects and develop interventions to reduce mortality.

Disclosures
All authors: No reported disclosures.
2697. The Impact of Universal Deceased Donor Screening on Donor-Derived Toxoplasmosis in Solid-Organ Transplant: Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC)
Authors: Strasfeld Lynne , La Hoz Ricardo M , Vece Gabe , Wolfe Cameron R , Michaels Marian G 
Published: October 2019

Abstract

Background
Donor-derived toxoplasmosis (DDT) is a severe and potentially life-threatening infection after solid-organ transplantation (SOT). Serologic testing for Toxoplasma gondii is required for all deceased donors per OPTN policy as of 4/6/17. To assess the impact of universal donor testing and the optimal approach to DDT prevention, we analyzed potential DDT cases reviewed by DTAC.

Methods
All potential Toxoplasma donor-derived transmission events adjudicated by DTAC from 2008 to 2018 were reviewed. A standardized classification algorithm was used to adjudicate each event as proven, probable, possible, unlikely, excluded or intervention without disease transmission.

Results
Twenty-eight potential DDT events were reported between 2008 and 2018. Proven or probable (p/p) DDT developed in 16 organ recipients from 15 donors. In the 9 years prior to the new testing requirement (January 2008–March 2017) 11 organ recipients from 10 donors had p/p DDT (0.13 transmissions per 1,000 donors); in the first 21 months of the new testing requirement 5 recipients from 5 donors had p/p DDT (0.27 transmissions per 1,000 donors), rate ratio 2.15; 95% CI 0.577, 6.90;P = 0.18. 10.2% of 18,328 donors tested between April 6, 2017 and December 31, 2018 were Toxoplasma IgG seropositive. Recipient pre-SOT serostatus was unknown in 4 of 5 and negative in 1 case of p/p DDT. Trimethoprim/sulfamethoxazole prophylaxis was either stopped at < 3 months or not used in all 5 cases. Infection was diagnosed a median of 103 days (range 42–153) post-transplant. Four of the 5 recipients died.

Conclusion
DDT remains a morbid infection in both heart and non-heart recipients. Despite an apparent increase in DDT reporting to DTAC, it is unlikely that the actual incidence of this donor-derived event is increasing. Rather, with universal serologic screening of deceased donors and wider access to molecular diagnostics, DDT is increasingly recognized and diagnosed. To decrease risk for illness and death related to DDT, broader pre-transplant recipient serologic testing and use of prophylaxis or monitoring for high-risk serostatus recipients (Toxoplasma D+/R−) is critical. The optimal duration of prophylaxis is uncertain at this time and warrants further study.

Disclosures
All authors: No reported disclosures.
2701. The Impact of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Children in British Columbia, Canada
Authors: Vadlamudi Nirma K , Patrick David , Hoang Linda , Marra Fawziah 
Published: October 2019

Abstract

Background
A significant reduction in invasive pneumococcal disease (IPD) has been reported following implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) infant immunization program, but not much has been reported after introduction of the 13-valent vaccine (PCV13). This study represents the effect of PCV13 on IPD in British Columbia, Canada over a 14 year period (2002–2015).

Methods
Using provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in children less than 17 years of age. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression.

Results
A total of 697 cases were reported over the 14 year period. The overall annual incidence decreased from 10.9 cases per 100,000 population in 2002 to 4.64 cases per 100,000 population in 2015. While overall decline of IPD was 59% (IRR 0.41; 95% CI: 0.35–0.51) compared with baseline, this reduction was greatest after introduction of PCV7 (IRR 0.44; 95% CI: 0.37–0.53); the incremental change after introduction of PCV13 was non-significant (IRR 0.94; 95% CI: 0.78–1.13). The greatest reduction in IPD was in children <2 years of age (PCV13 vs baseline: IRR 0.19; 95% CI: 0.14–0.25), followed by children 3–5 years of age (PCV13 vs baseline: IRR 0.34; 95% CI: 0.21–0.56); no significant change was observed in 6–17 year olds.

Conclusion
While IPD rates have been significantly reduced since the introduction of the PCV vaccines, the impact of the additional 6 serotypes in the PCV13 vaccine is non-significant.

Disclosures
All authors: No reported disclosures.
2722. Effects of Sex, Age, and Race on Immunogenicity of MenB-FHbp, a Bivalent Meningococcal B Vaccine: A Pooled Evaluation of Clinical Trial Data
Authors: Beeslaar Johannes , Peyrani Paula , Maguire Jason , Eiden Joseph , Palmer Paul , Maansson Roger , Crowther Graham , Perez John L 
Published: October 2019

Abstract

Background
MenB-FHbp (bivalent rLP2086), a meningococcal serogroup B vaccine, is approved in several countries for adolescents and young adults. MenB-FHbp elicited robust immune responses and had an acceptable safety profile during an extensive clinical development program. Because immune responses to vaccines can vary by subject demographics, this subgroup analysis pooled data across 7 randomized MenB-FHbp clinical studies to evaluate potential differences in immunogenicity by sex, age, or race/ethnicity in a larger dataset relative to individual studies.

Methods
Data from subjects who received 120 µg MenB-FHbp at 0, 2, and 6 months and had valid immunogenicity results for 4 vaccine-heterologous test strains were included. Immune responses were evaluated by serum bactericidal assays using human complement (hSBA). Immunogenicity endpoints (assessed 1 month after dose 3) were percentages of subjects achieving ≥ 4-fold rise in hSBA titer against each strain, percentages achieving hSBA titers ≥ the lower limit of quantification (LLOQ) against each strain and against all 4 strains combined (composite response), geometric mean hSBA titers against each strain, and percentages achieving hSBA titers ≥ 1:4 (correlate of protection) against each strain.

Results
This analysis included 8026 subjects aged 10‒25 years (51.7% males, 80.7% adolescents aged 10‒18 years, 87.0% white, 9.3% black, 0.8% Asian, 3.0% other race). One month after dose 3, percentages of subjects achieving a ≥ 4-fold rise from baseline titer against each strain and achieving a composite response were similar across age and race (table). A marginally greater percentage of males vs. females achieved ≥ 4-fold rise in titer against each strain, but these differences were not considered clinically meaningful because of the high percentages of responders in both groups.

Conclusion
MenB-FHbp immunogenicity was similar across sex, age, and race in this pooled analysis, with high percentages of responders in all evaluated subgroups. The marginally lower response rates among females compared with males were not considered clinically meaningful. These findings support currently recommended MenB-FHbp vaccination practices without modification by sex, age, or race.
Funding: Pfizer

Disclosures
All authors: No reported disclosures.
165. Comparative Effectiveness of Oral Fluoroquinolones vs. β-Lactams for the Treatment of Patients with Enterobacteriaceae Bloodstream Infections
Authors: Bjork Lauren , Hopkins Teri , Yang Linda , Frei Christopher R , Jones Xavier , Cadena Jose , Walter Elizabeth 
Published: October 2019

Abstract

Background
Fluoroquinolones (FQ) are associated with unacceptable rates of adverse drug events (ADE) and drug resistance. Safe and effective alternative oral agents are needed for definitive treatment of Enterobacteriaceae bloodstream infections (BSI). This study aims to determine whether treatment failure rates were similar in patients who received FQ or β-lactams (BL) for stepdown treatment of Enterobacteriaceae BSI.

Methods
We conducted a retrospective cohort study comparing oral BL vs. FQ as definitive therapy for patients with BSI due to Escherichia coli, Klebsiella spp., or Proteus spp. Eligible patients were ≥18 years old with a monomicrobial BSI treated with a single definitive oral antibiotic. Patients with a total antibiotic treatment duration of <6 or >21 days were excluded. Groups were matched based on age and gender. The primary outcome was treatment failure defined as recurrence or all-cause mortality within 90 days with a 10% non-inferiority margin. Secondary outcomes were death or recurrence within 30 and 90 days, symptomatic urinary tract infection (UTI) or BSI within 30 days, and the safety outcome of antibiotic-related ADE.

Results
The average age was 68 years, with 94% males. In the BL group, 80% had a urinary source of infection vs. 69% of the FQ group. The majority of patients had source control (88% of BL group vs. 83% of FQ group). The most common pathogens were E. coli (66%) and K. pneumoniae (24%). Cefpodoxime (71%) and ciprofloxacin (85%) were the most commonly used oral antibiotics. The average duration of oral therapy was 9.2 vs. 9.6 days and total duration was 14.4 vs. 13.9 days in the BL vs. FQ group, respectively. The primary outcome occurred in 15.4% of the BL group vs. 12.3% of the FQ group (P = 0.8002, RR = 0.80, 95% CI = 0.33–1.90). No deaths were directly attributed to infection. Symptomatic UTI or BSI within 30 days occurred in 20% of BL patients vs. 21.5% of FQ patients (P = 1.0000, RR = 1.07, 95% CI = 0.55–2.11). Mortality or recurrence at 30 days were similar between groups (4.6% of BL group vs. 9.2% of FQ group, P = 0.4920, RR = 2.00, 95% CI = 0.52–7.66). One FQ patient experienced an antibiotic-related ADE (C. difficile infection).

Conclusion
BL are non-inferior to FQ and appear to be as effective for oral step-down treatment of Enterobacteriaceae BSI without the associated risks.

Disclosures
All authors: No reported disclosures.