bluuebunny/crossref_metadata_2025_split huggingface dataset:
2232. A Global Phase 3 Study of Delafloxacin (DLX) Compared with Moxifloxacin (MOX) in Patients with Community-acquired Bacterial Pneumonia (CABP)
Authors: Salata Robert , Alvarez-Sala Rodolfo , Horcajada Juan P , Lawrence Laura , Quintas Megan , Li Yang , Cammarata Sue 
Published: October 2019

Abstract

Background
DLX is an IV/oral fluoroquinolone with no QT restrictions, and activity against Gram-positive, Gram-negative and atypical pathogens. DLX is approved for treatment of ABSSSI including those due to MRSA and Gram-negative pathogens. A Phase 3 trial of patients with CABP was recently completed.

Methods
Global active-comparator double-blind trial; adults with CABP with at least 2 clinical symptoms, physical signs, and radiographic evidence of pneumonia. Randomized 1:1 to DLX or MOX treatment for 5–10 days. Randomization stratified by PORT Class, history of COPD/asthma, and prior single-dose antibiotic use (limit 25%). Patients received a minimum of 3 days IV treatment, then were switched to oral at MD discretion. The primary endpoint for FDA was the Early Clinical Response (ECR): improvement at 96 hours after first dose of study drug in at least 2 of the baseline symptoms in the Intent to Treat (ITT) population.

Results
859 patients were randomized; both groups were comparable. Patient characteristics: mean age 60 (range 18–93, 21% ≥ age 75); 58.7% male; 28.6% multi-lobar pneumonia; 26.8% PORT class IV/V. Bacterial pathogens were identified in 60.5% at baseline; most commonly S. pneumoniae, as well as S. aureus, atypicals and Gram-negatives. Patients received treatment ~ 8.5 days (6.3 days of IV, 2.2 days oral). DLX was non-inferior to MOX in ECR 88.9% DLX vs. 89.0% MOX [∆−0.2 (CI -4.4, 4.1)] in the ITT population; ECR in the evaluable population was 91.1% DLX vs. 91.8% MOX [∆−0.6 (CI -4.5, 3.2)]. Day 28 Mortality was 1.9% DLX vs. 1.4% MOX. In the micro evaluable population, DLX was comparable to MOX in eradication, 92.5% DLX vs. 93.5% MOX at Test of Cure 5–10 days after treatment, [∆ −1.0 (CI -5.8, 3.6)]. 30.5% DLX and 26.2% MOX patients had ≥1 treatment-emergent adverse events (AEs). The most common DLX AEs were diarrhea and transaminase elevations, which were mild-to-moderate and did not routinely lead to discontinuation (DC). Treatment DC due to treatment-related AEs was seen in 9 DLX and 4 MOX patients. There were no potential QT AEs with DLX.

Conclusion
IV/oral DLX was comparable to IV/oral MOX for treatment of CABP in patients. DLX has no preclinical signals for QT prolongation and has no QT prolongation in a validated challenge study. DLX appears effective and well tolerated in patients with CABP.

Disclosures
All authors: No reported disclosures.
2235. Fecal Biomarkers for Clostridioides difficile Infection in Cancer Patients
Authors: Olvera Adilene , Yepez Guevara Eduardo , Garey Kevin W , Dillon Ryan J , Okhuysen Pablo C 
Published: October 2019

Abstract

Background
The diagnosis of C. difficile infection (CDI) relies on using a nucleic acid amplification test (NAAT) followed by confirmatory toxin enzyme immunoassay (EIA). This study examined the utility of fecal biomarkers and C. difficile bacterial quantity (BQ) in differentiating patients with true infection (NAAT+/EIA+) from patients with colonization (NAAT+/EIA-) in the context of C. difficile ribotypes.

Methods
We studied 136 patients with diarrhea and CDI identified by NAAT in stools for which a confirmatory toxin A, B, EIA was performed. Fecal IL-8, IL-1β, calprotectin, and lactoferrin were studied by ELISA. C. difficile BQ was determined by 16S rRNA qPCR. Data were stratified according to cancer diagnosis into three groups [hematologic (H) n = 43, solid tumor (ST) n = 62, or stem cell transplant (SCT) n = 31].

Results
Stools were EIA+ in 36/136 (26%) of the cohort. Although ST patients had a higher Charlson co-morbidity index when compared with the other two groups (P < 0.002), demographic characteristics and symptoms at the time of presentation were similar between groups regardless of EIA status. Most common ribotypes identified included F106 and F014-020. Ribotype distribution differed according to oncologic diagnosis as determined by the Shannon diversity index. There were fewer distinct C. difficile ribotypes in the SCT (n = 8) vs. ST (n = 15) and H (n = 15) groups (P < 0.001 and P < 0.002, respectively). BQ were higher in EIA+ than EIA- across all strata (log of BQ/mg 2.38 ± 1.49 vs. 0.92 ± 1.28, P > 0.001). Similarly, higher levels of fecal IL-8 (1.72 ± 1.9 vs. 0.83 ± 1.6 ng/mL), IL-1β (3.74 ± 13.7 vs.. 1.21 ± 4.6) and calprotectin (14.9 ± 27 vs. 6 ±1.8 ug/mL) levels were seen in EIA+ patients. While IL-8, IL-1β, and calprotectin were increased in EIA+ ST and H, no differences were seen in the SCT group. A sensitivity analysis using ROC curves, revealed that BQ resulted in a greater area under the curve than fecal markers of inflammation (A = 0.77, P < 0.001, 95% CI [0.67–0.86]).

Conclusion
In this study in cancer and immunocompromised patients, C. difficile bacterial burden regardless of infecting ribotype and fecal cytokines showed to be a helpful assay in distinguishing true CDI from colonization.

Disclosures
All authors: No reported disclosures.
2238. Evaluation of Adjuvant Interferon-Gamma-Level Assessment to Improve the Performance of Procalcitonin Testing in Hospitalized Bacteremic Patients
Authors: Ololade Shafiu O , Patel Kavya , Lafarga Derek G , Apewokin Senu K 
Published: October 2019

Abstract

Background
Although procalcitonin-guided antimicrobial stewardship has had proven utility in emergency and ICU settings, it is still not widely adopted outside these areas. One limitation to a more universal uptake has been the unreliable performance in discriminating bacterial infected from uninfected individuals. Viral infections have been noted to suppress procalcitonin (PCT) levels through Interferon-gamma (IFN-G)-mediated inhibition of procalcitonin release from parenchymal cells. Unfortunately, clinical application algorithms do not assess INF-G levels at the time evaluation thus treating providers are unable to distinguish a true-negative test from a false-negative test resulting from INF-G-mediated procalcitonin suppression This undermines the performance of PCT, particularly in patients with bacterial and viral co-infections. We hypothesized that adjuvant interferon gamma testing could improve the performance of PCT. To test this hypothesis we prospectively enrolled bacteremic hospitalized patients along with culture-negative controls and then assessed the performance of PCT with adjuvant IFN-G testing.

Methods
69 hospitalized patients with bacteremia and 32 culture-negative controls were enrolled. Demographic and clinical parameters were compared between groups alongside INFG and PCT levels Parametric and non-parametric statistical tests were performed where appropriate. Test performance was evaluated by constructing receiver operator curves (ROCs) for PCT, INF-G, and a combination of PCT+INF-G.

Results
Of 101 patients enrolled, the mean age was 49.46 ± 13.6 years with 47% being female. The following were comparative statistics between the culture-positive vs. culture-negative group: mean age 52.1 ± 15.7 vs. 46.4 ± 14.2 years, P = 0.56; WBC 11.9 ± 9.5 vs. 9.5±5.1, P = 0.170; ANC 8,466 ± 5,686 vs. 8,189 ± 4,769, P = 0.907; eGFR 73.2 ± 23 vs. 74.5 ± 26.1, P = 0.644; PCT 2.79 ± 5.87 vs. 0.71 ± 1.79, P = 0.03. Of these 57 patients had INF-G and PCT values available and their corresponding ROCs are shown in figure.

Conclusion
Our interim results indicate adjuvant INF-G testing may not improve the performance of procalcitonin in hospitalized bacteremic patients. The additional samples are being analyzed to confirm these findings.

Disclosures
All authors: No reported disclosures.
117. Hospitalized Burn Patients with Fever and Leukocytosis: Blood Culture or Not?
Authors: Luo Ruihong , Janoian Paul 
Published: October 2019

Abstract

Background
Fever and leukocytosis are very common in patients with burn injury. Many patients had to do blood cultures frequently during their hospitalization given the concern of bacteremia. We opt to utilize the clinical characters of the patients to evaluate the risk for bacteremia and avoid unnecessary blood culture.

Methods
The adult patients (≥18 years) with burn injury were selected from the Nationwide Inpatient Sample database (2005–2014). Using ICD-9 codes, we further identified bacteremia, total body surface area (TBSA) of burn, inhalation injury, pneumonia, urinary tract infection, wound infection, escharotomy, placement of central venous line, indwelling urinary catheter, gastrostomy tube (G-tube), intubation, and total parenteral nutrition (TPN). The risk factors for bacteremia were evaluated by Logistic regression. A risk-adjusted model to predict the occurrence of bacteremia was developed by discriminant analysis.

Results
In total, 241,323 hospitalized patients with burn injury were identified. The incidence of bacteremia was 1.1% (n = 2,634). Comparing with the patients without bacteremia, those with bacteremia were older (51.1 vs. 46.7 year old, P < 0.001), had more severe burn injury (50.7% vs. 12% with burn TBSA over 20%, P < 0.001) and comorbidities (22.7% vs. 14.9% with Charlson index ≥2, P < 0.001), higher in-hospital mortality (5.6% vs. 3.7%, P < 0.001), longer hospital stay (26 vs. 5 days, P < 0.001) and more hospital charges ($206,028 vs. $30,339, P < 0.001). When the age, sex, race, and Charlson index of the patients were adjusted by Logistic regression, it was found that the factors of inhalation injury (OR = 1.25, 95% CI 1.03–1.51), intubation (OR = 1.62, 95% CI 1.44–1.82), TPN (OR = 1.56, 95% CI 1.16–2.11), placement of central venous line (OR = 1.86, 95% 1.57–2.01), and G-tube (OR = 2.04, 95% CI 1.60–2.60) were associated with increased risk for bacteremia. A risk-adjusted model composed of the patient’s age, Charlson index, burn TBSA, inhalation injury, intubation, TPN, placement of central venous line, and G-tube could predict the occurrence of bacteremia with an accurate rate of 85.4% (Table 1).

Conclusion
The risk factors and risk-adjusted model for bacteremia may assist to decide whether a blood culture is needed in the hospitalized burn patients.

Disclosures
All authors: No reported disclosures.
2244. Clinical Outcomes with Extended Infusion (EI) vs. Intermittent Infusion (II) of Cefepime (FEP), Piperacillin/Tazobactam (TZP), and Meropenem (MEM) in Patients with Gram-Negative (GN) Bacteremia
Authors: Tran Kieu-Nhi , Mynatt Ryan , Kaye Keith S , Pogue Jason M 
Published: October 2019

Abstract

Background
The increase in drug-resistant pathogens has prompted interest in dosing of β-lactams (BLs) via EI. Available data on this practice are conflicting, rarely assess non-critically ill patients or low MIC pathogens, and do not focus on outcomes other than clinical cure or mortality. Further assessment of this practice is warranted.

Methods
This is a retrospective cohort study of adult patients who received FEP, TZP, or MEM for GN bacteremia via INI or EI from 2010 to 2018. Patients were included if the pathogen was susceptible to the target BL and they received study drug within 24 hours of bacteremia onset and continued it for ≥ 48 hours. Patients were excluded if they had a mixed infection or received > 48 hours of combination therapy. Patients were matched 1:1 based on study drug utilized, sepsis severity, ICU status, bacteremia source, and causative pathogen. Outcomes assessed included time to clinical stabilization as well as treatment failure, mortality, length of stay (LOS), and recurrence.

Results
268 patients (134 matched patients in each group) were included. Median (IQR) age of the cohort was 64 (55–77) years, and 57% were male. Common comorbidities were diabetes (35%) and CKD (26%), and the median (IQR) Charlson Comorbidity Index (CCI) was 3 (1–4). 40% of the population presented with severe sepsis or septic shock, and 42% were in the ICU at infection onset. Baseline characteristics were similar between the two groups except patients receiving EI were older (65.5 (58–78) vs. 61.5 (52–73); P = 0.006 and had higher median CCI (3 (2–4) vs. 2 (1–3); P < 0.001,) while patients in the II group had a higher mean weight (85.5 ± 27.8 vs. 78.8 ± 19.2, P = 0.02.) The most common organisms isolated were E. coli(41%), K. pneumoniae (18%), and P. aeruginosa (13%), and the most common source of infection was the urine (51%). Outcomes are listed in Table 1. EI was associated with decreases in time to defervescence, WBC normalization, and SIRS resolution. Furthermore, EI was associated with a lower incidence of treatment failure and recurrence as well as decreases in LOS and ICU-LOS. There was no difference in mortality.

Conclusion
The findings of this analysis highlight the role of EI in BL therapy as an important stewardship strategy to optimize clinical outcomes in all patients with GN bacteremia.

Disclosures
All authors: No reported disclosures.
2268. Clinical Implications of Azole-Resistant vs. Azole-Susceptible Invasive Aspergillosis in Hematological Malignancy (CLARITY): A Multicenter Study
Authors: Seidel Danila , Cornely Oliver , Arenz Dorothee , Meis Jacques , Vehreschild Jörg , Salmanton-Garcia Jon , Zarrouk Marouan , Falces Romero Iker , Racil Zdenek , Lagrou Katrien , Maertens Johan , Reséndiz Sharpe Agustìn , Blennow Ola , Lass-Flörl Cornelia , Legovic Yohann , Ostojic Alen , Desoubeaux Guillaume , Alakel Nael , Schalk Enrico , Bergeron-Lafaurie Anne , Steinmann Jörg , Buchheidt Dieter , Stanzani Marta , Klimko Nikolai , Prattes Jürgen , Melchers Willem , Vehreschild Maria , Verweij Paul 
Published: October 2019

Abstract

Background
In recent years, survival of patients with invasive aspergillosis (IA) has improved mainly due to availability of extended spectrum triazoles. These advances are jeopardized by the emergence of azole resistance in Aspergillus fumigatus, the most common causative pathogen of IA. Despite several studies suggesting high probability of azole treatment failure in patients with azole-resistant isolates, the clinical implications of azole-resistant IA compared with azole-susceptible IA remain unclear.

Methods
In patients with hematological malignancies, cases of proven or probable IA (EORTC/MSG 2008) caused by A. fumigatus are registered. Retrospective data are documented, comprising demographics, diagnosis, treatment, response and outcome. Participating sites provided susceptibility results or isolates. Provided isolates were analyzed in a central laboratory.

Results
Since January 2018, 51 sites in 15 countries worldwide enrolled 154 cases diagnosed with IA between 2010 and 2019, of which 23 (14.9%) had azole-resistant IA. Of 44 cases, the respective clinical fungal isolate was analyzed in the central laboratory. A mixed fungal infection was reported for 34 patients (22.1%), 1 (2.9%) in the azole-resistant group; most were related to non-fumigatus Aspergillus species (n = 12, 35.3%) and non-Aspergillus molds (n = 10, 29.4). Most patients were male (n = 98, 63.6%); 19 (82.6%) in the azole-resistant group, 79 (60.3%) in the azole-susceptible group. Age was documented in categories instead of the exact age. Median age group was 50–69 years in both groups (ranging from 7–11 to 70–89 years for azole-resistant cases, 1–12 months to 70–89 years for azole-susceptible cases). Underlying disease and survival are shown in the table.

Conclusion
A worldwide network of investigators contributes to the CLARITY registry study. Completion of recruitment and subsequent data analysis are planned for 2019. Further sites may be added if azole-resistant cases are encountered.

Disclosures
All authors: No reported disclosures.
2269. Clinical Outcomes in Patients with Carbapenem-Non-Susceptible, β-Lactam-Susceptible Pseudomonas aeruginosa Infections
Authors: Gavaghan Victoria M , Lee Michelle , Butler David , Biagi Mark , Santarossa Maressa , Harrington Amanda , Albarillo Fritzie S , Wenzler Eric 
Published: October 2019

Abstract

Background
Pseudomonas aeruginosa (PsAr) isolates harboring OprD mutations often present phenotypically as carbapenem nonsusceptible but susceptible to antipseudomonal β-lactams (APBLs). It is unknown whether this unique genotype–phenotype combination affects the clinical outcomes of patients infected with these pathogens. The objective of this study was to compare clinical outcomes of patients treated with APBLs for pneumonia and/or bacteremia caused by PsAr bearing this unique carbapenem nonsusceptible, β-lactam susceptible phenotype (Carba-NS) to those retaining susceptibility to both carbapenems and APBLs (Carba-S).

Methods
Retrospective multicenter cohort of adult in-patients who received effective APBL for PsAr pneumonia and/or bacteremia from January 2012 to November 2018. Baseline characteristics, treatment information, and clinical outcomes were obtained from the electronic medical record. The primary outcome was 14-day mortality. Secondary outcomes included 30-day mortality, 30-day infection recurrence, and infection-related length of stay (IR-LOS). IR-LOS was defined as the time from index culture to antibiotic discontinuation or hospital discharge, whichever was sooner. Descriptive statistics were analyzed using SPSS.

Results
387 patients were evaluated; 60 Carba-S and 21 Carba-NS were included. The primary reason for exclusion was ineffective empiric therapy. Select demographics and clinical outcomes are displayed in Table 1. Compared with the Carba-S group, Carba-NS patients were younger, had better renal function, increased incidence of pneumonia, more severely ill, and higher rate of empiric ceftazidime use. Despite these differences at baseline there were no significant differences in empiric APBL treatment patterns, 14- or 30-day mortality, or recurrence at 30 days between the groups. Carba-NS patients had lower rate of oral step down therapy and a significantly longer LOS and IR-LOS.

Conclusion
In this cohort of patients who received appropriate and timely APBL therapy, the Carba-NS phenotype was not associated with increased rates of 14-day mortality, 30-day mortality, or 30-day infection recurrence. These data suggest that APBLs may be effective therapeutic options against this phenotype. Further research is warranted to confirm these findings.

Disclosures
All authors: No reported disclosures.
2276. Clinical Epidemiology of the Carbapenem-Resistant Enterobacteriaceae (CRE) Epidemic in Colombia: A Multicenter Prospective Study
Authors: Valderrama-Beltrán Sandra Liliana , Komarow Lauren , Salcedo Soraya , Mora Laura , Marin Adriana , Ordonez Diaz Karen M , Cristancho Quintero Edilberto , Elena Ariza Beatriz , Cortes Gloria , la Hoz Alejandro De , Oñate José , Yasmín Venté Elsa , Mendez Viviana , Figueroa Jairo , Osorio Luz , Moreno Carlos , Reyes Jinnethe , Dulcey Luis , Christian Pallares , Chambers Henry , Chambers Henry , Fowler Vance G , Evans Scott R , Kreiswirth Barry , Virginia Villegas Maria , Bonomo Robert A , van Duin David , Arias Cesar A 
Published: October 2019

Abstract

Background
The CRE epidemic in Colombia is amplified by horizontal transmission of mobile genetic elements encoding KPC among Enterobacteriaeae and clonal expansion of K. pneumoniae clonal group (CG) 258, making the country hyperendemic for CRE. However, the clinical impact of CRE infections has not been comprehensively assessed.

Methods
In the framework of a prospective study assessing the clinical epidemiology of CRE (CRACKLE II), we report the results of the first 246 patients enrolled in 5 Colombian hospitals (from July 2017 to November 2018). Clinical variables, outcomes at 90 days post-hospitalization and susceptibility patterns were collected. Resistance to carbapenems was defined per CDC guidelines. Infection was defined with standardized criteria. All isolates which did not meet these criteria were considered colonization

Results
The majority of patients were men (66%); median age was 62 years [IQR 37–73]); 67% were admitted from home and 33% were hospital transfers. The mean Charlson Comorbidity Index and Pitt Bacteremia scores were 2 (SD = 2) and 3 (SD = 3), respectively. Most patients (60%; n = 148) were considered to be infected. The most frequent source of culture was urine (36%), followed by blood (30%) and wound secretions (13%). A respiratory source was found in the minority (6%) of patients. Species of CRE are summarized in Table 1 with the majority being K. pneumoniae. The best in vitro activity against CRE was found for fosfomycin (80% susceptible (47/59)), tigecycline (75% (67/89)), colistin (70% (35/50)) and amikacin (67% (148/220)). From 234 patients with available information at 90 days of follow-up, 13% were readmitted after discharge. Mortality at 30 and 90 days after a positive culture was 31% and 35%, respectively.

Conclusion
K. pneumoniae are the main drivers of the CRE epidemic in Colombia isolated mainly from non-respiratory sources. Non-susceptibility to last resource antibiotics (tigecycline, colistin and fosfomycin) is substantial among the Colombian isolates leaving few therapeutic options, a finding that correlates with high mortality. Our findings indicate that introduction of novel therapeutics in Colombia is urgently needed with a rampant epidemic of CRE causing high burden of disease.

Disclosures
All authors: No reported disclosures.
2287. Real-world Use of Tedizolid Phosphate: A Case Series of Long-Term Tolerability
Authors: Morrisette Taylor , Da Silva Beatriz , Mueller Scott W , Damioli Laura , Krsak Martin , Fish Douglas N , Miller Matthew A 
Published: October 2019

Abstract

Background
Tedizolid is an oxazolidinone antibiotic with broad-spectrum Gram-positive activity approved for the treatment of skin and skin structure infections with a 6-day course. Oxazolidinone antibiotics represent appealing options for prolonged antimicrobial therapy due to their available oral formulations with excellent bioavailability and potent in vitro activity against various multidrug-resistant Gram-positive organisms, Mycobacterium spp., and Nocardia spp. Although tedizolid and linezolid offer a similar clinical spectrum based on antimicrobial activity alone, long-term use of linezolid is often limited by serious adverse effects. Preliminary assessments have suggested better tolerability with tedizolid; however, these are limited by shorter exposure duration. The objective of this study was to evaluate the long-term safety and tolerability of tedizolid.

Methods
Retrospective cohort of adult patients receiving tedizolid for ≥ 28 days, with baseline complete blood cell (CBC) indices available, and CBC indices drawn ≥ 14 days into tedizolid course. The primary objective was to evaluate the long-term tolerability of tedizolid.

Results
13 patients met inclusion criteria: median age 61 years (IQR, 51–64 years), 69% male, 85% Caucasian. The majority of patients utilized tedizolid for suppression (85%), and the median duration of tedizolid was 113 days (IQR, 71–204 days). There were no differences in CBC indices when comparing baseline to last laboratory draw throughout tedizolid exposure: platelets (baseline: 203 x 109/L (IQR, 186–283 x 109/L) vs. last: 196 x 109/L (IQR, 161–303 x 109/L; p = 0.65), hemoglobin (baseline: 9.8 g/dL (IQR, 8.8–11.1 g/dL) vs. last: 11.7 g/dL (IQR, 11.0–13.1 g/dL; p = 0.10), and white blood cells (baseline: 6.2 x 109/L (IQR, 5.6–7.6 x 109/L) vs. last: 6.5 x 109/L (IQR, 6.3–7.3 x 109/L; p = 0.45). The final laboratory draws were obtained a median of 78 days (IQR, 44–119 days) into therapy. No patients experienced peripheral neuropathy, optic neuritis/visual changes, or serotonin syndrome during treatment/suppression with tedizolid during the period evaluated.

Conclusion
Long-term therapy with tedizolid appears to be well-tolerated. Treatment and suppression with tedizolid seems to be a safe alternative to linezolid.

Disclosures
All authors: No reported disclosures.