bluuebunny/crossref_metadata_2025_split huggingface dataset:
2160. Performance of the Cepheid Rapid PCR Test for Patient Screening and Association with Efficacy of Suvratoxumab, A Novel Anti-Staphylococcus aureus Monoclonal Antibody, During the Phase 2 SAATELLITE study
Authors: Ruzin Alexey , Yu Li , Barraud Olivier , François Bruno , Sánchez Garcia Miguel , Eggimann Philippe , Dequin Pierre-Francois , Laterre Pierre-François , Huberlant Vincent , Viña Lucia , Boulain Thierry , Bretonnière Cédric , Pugin Jérôme , Trenado Álvarez José , Catalina Hernandez Padilla Ana , Vignaud Julie , Vandamme Drieke , Ali Omar , Shoemaker Kathryn , Colbert Susan , Sellman Bret R , McCarthy Michael , Jafri Hasan S , Esser Mark T 
Published: October 2019

Abstract

Background
Patients with lower airway Staphylococcus aureus (SA) colonization are at great risk (> 20%) of early-onset ventilator-associated pneumonia (VAP). Thus, a rapid test is required to identify patients at risk. Suvratoxumab (formerly MEDI4893) is a human monoclonal antibody that neutralizes SA alpha toxin. SAATELLITE, a phase 2 study of safety and efficacy of suvratoxumab for reducing the incidence of SA pneumonia (NCT02296320) was conducted and recently completed within the consortium for Combatting Bacterial Resistance in Europe. We investigated the performance of a rapid PCR test (Xpert MRSA/SA SSTI™, Cepheid) as a screening tool during the study and the association between SA load and suvratoxumab efficacy.

Methods
The PCR assay was used to detect SA and methicillin-resistant SA (MRSA) in lower respiratory tract (LRT) samples. Culture was performed on PCR SA+ LRT samples according to local procedures. PCR SA+ subjects were randomized 1:1 to either a single intravenous infusion of 5000 mg suvratoxumab (n = 96) or placebo (n = 100) and followed for 190 days post dose. Efficacy of suvratoxumab was defined as relative risk reduction (RRR) in incidence of SA pneumonia within 30 days post-dose compared with placebo.

Results
299 (41.5%) out of 720 screened subjects were SA+ by PCR. Of 209 subjects with culture data, there were 162 (77.5%) SA+, 47 (22.5%) SA- and 9 (5.6%) MRSA by culture. Culture results could have been affected by antibiotic use and site variability in limits of detection ranging from 3.3 to 100,000 colony-forming units per mL (CFU/mL). No discordance was noted between PCR and culture for MRSA detection. An inverse linear correlation was observed between the PCR cycle threshold (Ct) values for SA protein A gene (spa) and SA CFU/mL counts from quantitative culture. In subjects with low SA load (Ct ≥ 29; n = 72), suvratoxumab provided 66.7% RRR [90% confidence interval (CI): 21.3%, 86.2%] compared with 31.9% RRR [90% CI: -7.5%, 56.8%] in total study population.

Conclusion
Cepheid Xpert PCR assay was easy to perform, sensitive and standardized, and provided better sensitivity than conventional culture for detection of SA. Additionally, quantitative PCR Ct output was associated with the efficacy of suvratoxumab in reducing SA pneumonia incidence.

Disclosures
All authors: No reported disclosures.
2175. Rapid Detection of Carbapenemase Producing Organisms Directly from Blood Cultures Positive for Gram-Negative Bacilli
Authors: Stokes William , Pitout Johann , Campbell Lorraine , Church Deirdre , Gregson Dan 
Published: October 2019

Abstract

Background
The rapid detection of carbapenemase-producing organisms (CPOs) directly from blood cultures (BC) positive for Gram-negative bacilli (GNB) may accelerate the appropriate treatment of at-risk patients. Our objective was to evaluate the performance of two commercial assays in the rapid detection of CPOs directly from BC positive for GNB.

Methods
BC positive for GNB, taken from patients within the Calgary Health Zone over a 3 month period, were tested for the presence of CPOs with βCARBA® and NG-Test® CARBA 5. A subset of sterile BC samples was seeded with multi-drug-resistant (MDR) GNB. BC were incubated using the Bact-Alert™ system. Positive BC from clinical and seeded samples was tested directly with βCARBA and CARBA 5 from BC pellets processed for direct testing using an ammonium chloride lysis and wash method. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated with 95% confidence intervals for binomial proportions.

Results
65 samples were tested (30 clinical, 35 seeded). Seeded samples included 1 GES, 4 IMP, 6 KPC, 1 co-producing KPC and NDM, 9 OXA, 4 VIM, 5 NDM, and 5 non-CPO carbapenem-resistant organisms. βCARBA had a sensitivity, specificity, NPV and PPV of 100% (88.4% - 100%), 65.7% (47.8–80.9%), 100%, and 71.4% (61.3%–79.8%), respectively. CARBA 5 had a sensitivity, specificity, NPV and PPV of 90.0% (73.5%–97.9%), 100% (90.0%–100%), 92.1% (80.0%–97.2%), and 100%. When excluding GES, which is known not to be detected by CARBA 5, sensitivity and NPV increased to 93.1% (77.2%–99.2%) and 93.1% (78.0%–98.1%), respectively. False negatives for βCARBA occurred with 1 VIM-1 and IMP-14.

Conclusion
This study demonstrates that the detection of CPOs directly from positive BC can be accurately achieved. βCARBA had excellent sensitivity but suffered from poor specificity. CARBA 5 had good sensitivity and specificity but is unable to detect certain CPOs. Testing positive BC directly using βCARBA and/or CARBA 5 may be useful in rapidly detecting CPOs. Results of direct testing from the CARBA5 assay would quickly identify patients amenable to treatment with avibactam combination compounds.

Disclosures
All authors: No reported disclosures.
2178. Sensitivity of Blood Cultures in Detection of Bacteremia in Febrile Neutropenia
Authors: Patel Vanisha , Ferrolino Jose Amadeo A , Hayden Randall , Hayden Randall , Gaur Aditya H 
Published: October 2019

Abstract

Background
Febrile neutropenia (FN) secondary to bacteremia is a treatable complication of chemotherapy that increases mortality if not promptly recognized and managed.

Methods
The sensitivity of blood cultures collected in pediatric oncology patients with FN was assessed and stratified based on the day of FN episode, culture media type, and the source of blood culture draw at a single US center between 2013 and 2018. Paired aerobic and lytic media bottles were inoculated with each culture draw using a weight-based volume of blood; anaerobic cultures were included with initial cultures starting in September of 2015.

Results
In a retrospective analysis of 10,596 patients, a total of 3,039 episodes of FN were identified. Of the FN episodes, 17.7% had at least one positive blood culture; 84.5%, 1.3%, 0.9% and 13.3% of positive cultures were collected on day 0, day 1, day 2 and ≥ day 3 of a febrile episode. Among the positive day 0 cultures, the median time to detection of an organism was 14.1 hours. Host characteristics of blood culture-positive FN episodes are summarized in Table 1. Bacteremia was identified in 537 FN cases; 18.1%, 11.9% and 2.6% of cultures were positive in only aerobic, lytic or anaerobic media cultures, respectively. The most commonly isolated organisms were Escherichia coli, coagulase-negative Staphylococcus, viridans group streptococcus, Klebsiella pneumoniae and Pseudomonas aeruginosa. Fifteen percent of infectious episodes with a positive blood culture were polymicrobial.

Conclusion
In summary, the study findings have important clinical implications such as emphasizing the value of day 0 cultures and highlighting the importance of routinely collecting blood cultures in more than one media type. Despite an optimized blood culture approach, less than a fifth of FN episodes had a blood culture-based diagnosis.

Disclosures
Randall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board.
111. Pediatric and Adolescent Sepsis Epidemiology and Clinical Characteristics, Emerging Infections Program, 2014–2015
Authors: Gokhale Runa Hatti , Sapiano Matthew , Dantes Raymund , Abanyie-Bimbo Francisca , Wilson Lucy E , Thompson Nicola , Perlmuter Rebecca , Nadle Joelle , Frank Linda , Brousseau Geoff , Johnston Helen , Bamberg Wendy M , Dumyati Ghinwa , Lynfield Ruth , DaSilva Malini , Kainer Marion A , Zhang Alexia Y , Ocampo Valerie , Samper Monika , Irizarry Lourdes , Sievers Marla M , Maloney Meghan , Ray Susan , Magill Shelley , Katz David , Epstein Lauren 
Published: October 2019

Abstract

Background
Sepsis is an important contributor to mortality among children and young adults. However, recent studies focused on hospital management and burden estimation do not provide critical data to inform prevention efforts. We conducted detailed medical record reviews to describe the epidemiology and clinical characteristics of children and young adults with sepsis to inform prevention and early recognition targets.

Methods
We utilized the Emerging Infections Program (EIP) to collect comprehensive data via retrospective record review for patients with severe sepsis or septic shock discharge diagnosis codes from a nonrandom sample of hospitals across 10 states. Children and young adults, aged 30 days through 21 years, discharged between September 30, 2014 and October 1, 2015, were randomly selected for inclusion. We performed a descriptive analysis of these data.

Results
Among 734 patients hospitalized with sepsis, 92% were living in a private residence 4 days before admission, 38% had an outpatient medical encounter in the 7 days before admission, 14% had sepsis onset after hospital day 3, and 11% died within 90 days of sepsis diagnosis. The most frequently identified infection was lower respiratory tract infection (14%); for 317 (43%) no infection was documented as a cause of sepsis. The most frequently identified pathogen was Staphylococcus aureus (10%); for 326 (44%) no pathogen was identified as a cause of sepsis. Among 394 (54%) patients with ≥1 chronic underlying medical condition (CUMC), the most common were pulmonary disease (35%), hematologic/oncologic disease (31%), immune compromise (24%), and cardiovascular disease (20%). Patients with CUMC had a higher percentage of their sepsis onset after hospital day 3, death within 90 days of sepsis diagnosis, and Pseudomonas aeruginosa as a cause of sepsis (table). The percentage of patients with no pathogen identified was similar between those with CUMC and those without.

Conclusion
In our large cohort of children and young adults with sepsis, most had sepsis onset outside of the hospital and over half had chronic conditions. Our data suggest that distinct approaches may be needed to develop effective prevention and early recognition strategies for children and young adults depending on the presence of chronic conditions.

Disclosures
All authors: No reported disclosures.
2203. Patient-Specific Risk Stratification to Identify Patients at High and Low Risk for P. aeruginosa in Community-Acquired Pneumonia
Authors: Justin Moore William , Cruce Caroline , Harkabuz Karolina , Salama Shereen , Sutton Sarah , Zembower Teresa , Postelnick Michael J , Wunderink Richard G , Rhodes Nathaniel J 
Published: October 2019

Abstract

Background
Pseudomonas aeruginosa (PsA) is an infrequent pathogen associated with poor outcomes in community-acquired pneumonia (CAP). Identifying patients at high and low-risk for PsA in CAP is necessary to reduce inappropriate and overly broad-spectrum antibiotic use. We evaluated the distribution of risk-factors in hospitalized CAP patients with and without PsA infection.

Methods
Design: retrospective, single-center, case–control study. Inclusion: hospitalized CAP patients admitted to the general medicine wards between January 1, 2014 and May 29, 2018. Exclusion: cystic fibrosis, ≥ 3 admissions within 30 days, CAP requiring ICU admission, and death within 48 hours of admission. Case patients had PsA in respiratory or blood cultures during the index CAP admission. Controls were randomly selected targeting a 3:1 ratio. Comorbidities, pneumonia severity index, and m-APACHE II were assessed. Gram-negative risk factors defined by Shindo et al. 2013 (PMID: 23855620) and validated by Kobayashi et al. (2018; PMID: 30349327) were scored for each patient. Stepwise logistic regression was used to identify covariates that distinguished cases from controls at a P < 0.2; these were then used to generate propensity weights (i.e., inverse-probability conditioned on covariates). Unadjusted and adjusted odds ratios for case status were estimated using logistic regression according to: the total number of risk factors present and threshold values, respectively. All analyses were conducted using IC Stata (v.14.2).

Results
54 cases and 152 controls were included. The distribution of the patient-specific sum of risk factors for PsA is shown in Figure 1. The univariate OR for case status was 4.29 (95% CI:1.55–11.9) at n = 3 risk factors, which was similar after propensity weight adjustment [aOR = 4.64 (95% CI: 1.32–16.3)]. The univariate OR of case status was 2.98 among patients with ≥ 3 risk factors (95% CI: 1.34–6.62), which was similar after propensity weight adjustment [aOR = 2.8 (95% CI: 1.02–7.72)], and correct classification was 73.8%.

Conclusion
At a threshold of ≥ 3 PsA risk factors, cases and controls were well classified, even after adjusting for propensity weights. The impact of patient-specific PsA risk-stratification on CAP outcomes and appropriate antibiotic use should be evaluated.

Disclosures
All authors: No reported disclosures.
2209. Charlson Comorbidity Index Scores and In-hospital Prognosis in Severe Acute Respiratory Infections Patients
Authors: Wisniewski Setter Nicholas , Latarini Peres Marcos , Machado de Almeida Bernardo Montesanti , Mara Raboni Sonia 
Published: October 2019

Abstract

Background
Respiratory infections are one of the leading causes of mortality, and comorbid conditions play a significant role in the severity and fatality of these infections. The Charlson Comorbidity index (CCI) is the most used comorbidity index, presenting a few updated versions since its establishment. In the present study, we evaluated the CCI score and possible predictors of mortality in hospitalized patients with Severe Acute Respiratory Infection (SARI), aiming to test whether the CCI is a valid in-hospital prognostic indicator.

Methods
Patients older than 14 years, hospitalized from 2010 to 2016 due to SARI by viral infection, and who were submitted to respiratory virus testing were included. We assessed comorbidity retrospectively through chart review, and calculated 4 variants of the CCI.

Results
Of the 291 patients assessed, 72.8% (n = 212) presented comorbidities and 24% died (n = 70). The most recurrent comorbidities were Chronic Pulmonary Disease (n = 76/212, 36%) and HIV (n = 50/212, 23.6%). Respiratory virus testing was positive in 38.1% of patients (n = 111), Influenza and Rhinoviruses being the most frequent. The 1994 Age-adjusted CCI predicted in-hospital mortality in SARI patients (P = 0.04), and HIV was independently associated with in-hospital mortality (P = 0.032).

Conclusion
The comorbidity scores used to assess mortality risk in hospitalized patients with SARI displayed poor results, but HIV infection was considered a marker of severity. However, other factors should be considered in order to compose a scoring system that allows us to specifically assess the risk of mortality in patients with SARI.

Disclosures
All authors: No reported disclosures.
2217. Frequency and Antimicrobial Susceptibility of Bacteria Isolated from Patients Hospitalized with Pneumonia in US Medical Centers During 2018
Authors: Sader Helio S , Huband Michael D , Carvalhaes Cecilia G , Castanheira Mariana 
Published: October 2019

Abstract

Background
Rapidly introducing appropriate antimicrobial therapy is crucial to reduce morbidity and mortality of patients hospitalized with pneumonia (PHP), and therapy is determined mostly by understanding causative pathogens. Ceftazidime–avibactam (CAZ-AVI) was recently approved and ceftolozane–tazobactam (C-T) is in late-stage clinical development for treating nosocomial pneumonia, including ventilator-associated.

Methods
Bacterial isolates were consecutively collected from PHP (1/patient) in 67 US medical centers in 2018 and the Gram-negative bacilli (GNB) were tested by reference broth microdilution methods for susceptibility (S) to CAZ-AVI, C-T, and many comparators at a central laboratory.

Results
The most common organisms isolated from PHP were S. aureus (27.0%), P. aeruginosa (PSA) (24.6%), K. pneumoniae (KPN; 7.6%), E. coli (6.8%), S. marcescens (5.4%), and S. maltophilia (XM; 4.5%). Colistin (99.7%S), CAZ-AVI (95.7%S), and C-T (94.9%S) were the most active compounds against PSA; CAZ-AVI (99.9%S), amikacin (AMK; 98.8%S), and meropenem (MEM; 97.6%S) were the most active compounds against Enterobacterales (ENT). CAZ-AVI and C-T retained activity against PSA isolates non-S (NS) to piperacillin–tazobactam (PIP-TAZ), MEM, and cefepime (FEP), whereas PSA isolates NS to PIP-TAZ, MEM, or FEP exhibited low S rates to PIP-TAZ (≤ 39.2%), MEM (≤ 37.8%), and FEP (≤ 38.0%; Table). CAZ-AVI and tigecycline were the only compounds with good activity against carbapenem-resistant ENT (CRE), both with 96.6%S. Among ENT, the most common ESBL and carbapenemase were CTX-M-15 (73%) and KPC-2/3 (76%), respectively. CAZ-AVI was active against all ESBL producers (100.0%S), whereas the S rate to C-T was 82.4%. The most active compounds against multidrug-resistant (MDR) ENT were CAZ-AVI (98.9%S), AMK (91.5%S), and MEM (80.8%S). XM and A. baumannii exhibited low S rates to most antimicrobials tested.

Conclusion
Gram-negative bacteria were isolated from 70% of PHP, and PSA and ENT represented >80% of these organisms. CAZ-AVI and C-T showed similar coverage (%S) against PSA (95.7–94.9%S). In contrast, C-T was less active than CAZ-AVI against ENT in general and exhibited limited activity against ENT-resistant subsets.

Disclosures
All authors: No reported disclosures.
2233. Efficacy and Symptom Resolution by Visit in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results
Authors: Schranz Jennifer , Das Anita F , Alexander Elizabeth , Moran Gregory J , Sandrock Christian , File Thomas M , Gelone Steven P 
Published: October 2019

Abstract

Background
Efficacy and safety of LEF were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the efficacy of LEF by visit based on a pooled analyses of LEAP 1/2 data.

Methods
In LEAP 1, PORT III–V patients (patients) received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF 600 mg q12h for 5 days or oral MOX 400 mg q24h for 7 days. Criteria for defining the FDA primary endpoint of early clinical response (ECR) at 96 ± 24 hours after first dose were applied to each visit through late follow-up (LFU; days 27–34) in the intent-to-treat (ITT; all randomized patients) population. Investigator assessment of clinical response (IACR) was examined at end of treatment (EOT; within 2 days after last dose), test-of-cure (TOC; 5–10 days after last dose; EMA primary endpoint), and LFU in the modified ITT (mITT; received ≥1 dose of study drug) and clinically evaluable (CE; met predefined evaluability criteria) populations. Results are presented by visit for pooled LEAP 1/2 data.

Results
1289 ITT patients were randomized (LEF, n = 646; MOX, n = 643). Most patients in both groups achieved ECR at Day 3, with further increases through Day 7 and sustained efficacy through LFU (Fig 1). In mITT patients, IACR success rates at EOT/TOC/LFU were 87.1/85.0/83.2% with LEF and 88.1/87.1/86.1% with MOX; results were consistent in CE patients. The proportions of ITT patients with resolution of all baseline signs/symptoms of CABP increased similarly by visit in both treatment groups (Fig 2). Most patients did not achieve complete sign/symptom resolution until TOC, with fever generally being the first and cough the last to resolve. There was no apparent relationship between ECR and age, gender, renal status, SIRS, PORT, prior antibiotic use, baseline pathogens, typical/atypical pathogens, or mono/polymicrobial pathogens. The high percentage of patients at LFU with baseline symptom resolution suggests that symptom resolution was sustained.

Conclusion
In this pooled analysis, efficacy results were similar by visit in the LEF and MOX groups, with high ECR rates maintained through LFU. LEF will provide a potential new effective systemic monotherapy alternative to fluoroquinolones for the empiric treatment of CABP.

Disclosures
All authors: No reported disclosures.
2237. Early Discontinuation of Antibacterials Is Safe for Patients with Community-Acquired Pneumonia (CAP) Who Have a Positive Viral Test, Negative Tests for Bacteria, and Low Procalcitonin
Authors: Politis Paula Ann , Kallstrom George , Tan Michael , File Thomas M 
Published: October 2019

Abstract

Background
Studies using molecular testing methods have found monomicrobial infection with a virus as the etiology of CAP in adult patients admitted to the hospital in 6–30% of cases. The use of antibacterial agents in such patients is unnecessary, and can lead to untoward consequences. A test confirming a viral etiology may reduce the needless use of antibiotics, especially if the procalcitonin (PCT) level is low, suggesting that bacterial co-infection is unlikely. Our Antimicrobial Stewardship Program (ASP) routinely follows patients admitted with respiratory tract infections, and provides recommendations for appropriate therapy based on diagnostic test results as well as PCT levels. We present a retrospective evaluation of our experience.

Methods
A retrospective review of ASP interventions on patients admitted to Summa Health System—Akron Campus was performed for the time frame of January 2018–March 2019. Patients were included if they had a positive viral PCR result (VERIGENE™, BioFire™), a PCT level <0.25 ng/mL (BioMérieux™, Abbott™), negative bacterial studies, and an accepted intervention to discontinue antimicrobial therapy made by the ASP.

Results
The ASP assessed 131 patients with positive viral PCR studies and low PCT levels who had antimicrobials discontinued based on ASP recommendations; 68 with CAP and 63 without pneumonia (WPNA) as demonstrated on imaging. Most patients in the WPNA category had acute exacerbation of COPD. Common viruses identified were Influenza A or B, Rhinovirus and RSV. Mean duration of antibiotics was 2.6 days for CAP and 2.4 days for WPNA (Table 1). The 30-day readmission rate was similar for each group, and for CAP patients was similar for all-cause pneumonia patients at our institution (14% during similar time period). 30-day Mortality of CAP patients was low.

Conclusion
While national guidelines recommend a minimum of 5 days of antimicrobial therapy for CAP patients, we have observed that discontinuing antibiotics well before that is safe if a viral etiology is identified without evidence of bacterial co-infection (including low PCT) and results in less antibiotic usage. Reduction in unnecessary antibiotic use has the potential to improve the quality of care for adults with CAP.

Disclosures
All authors: No reported disclosures.