bluuebunny/crossref_metadata_2025_split huggingface dataset:
2133. Clinical Impact of Implementation of Rapid Diagnostic Testing of Blood Cultures on Patient Outcomes
Authors: Gritte Anndee , Hopkins Teri , Morneau Kathleen , Frei Christopher R , Cadena-Zuluaga Jose , Walter Elizabeth 
Published: October 2019

Abstract

Background
Rapid diagnostic testing (RDT) in microbiology labs shortens the time to identification of bacteria in blood cultures. This study evaluates the impact of implementation of Cepheid® GeneXpert® to detect methicillin-resistant Staphylococcus aureus and S. aureus in Gram-positive blood cultures.

Methods
Patients with positive blood cultures for Staphylococcus spp. before (November 2015–August 2016) and after (November 2017–8/2018) implementation of a new rapid diagnostic technology were evaluated. RDT results were reviewed once daily by the antimicrobial stewardship team. The primary outcome was time to appropriate antimicrobial therapy. Secondary outcomes included the duration of antimicrobial therapy from time of positive culture, duration of vancomycin therapy, and length of hospital stay (LOS).

Results
A total of 113 patients were in the pre- and 73 patients were in the post-implementation cohort. Patients treated post-RDT demonstrated significantly shorter median time to appropriate therapy (20.6 hours vs. 49.8 hours, P = 0.03) and numerically shorter median duration of vancomycin therapy (3.0 days vs. 1.0 days, P = 0.32). These numerical differences were present despite the post-RDT cohort having significantly more MSSA and MRSA infections. Differences in duration of antimicrobial therapy were not statistically significant. Patients treated pre-RDT demonstrated a shorter median LOS than those treated post-implementation (7.0 days vs. 8.5 days, P = 0.03).

Conclusion
The use of RDT significantly decreased time to appropriate antimicrobial therapy. Patients in the post-RDT cohort had longer LOS, which may due to a higher incidence of S. aureus infections, compared with coagulase-negative Staphylococcus, in this cohort These results are promising for future RDT interventions.

Disclosures
All authors: No reported disclosures.
2139. Rickettsia typhi Detection in Clinical Infections by the Karius Test, a Plasma Microbial Cell-free DNA Next-Generation Sequencing Test
Authors: Centeno Fernando H , Ahmed Asim A , Hong David K , Dalai Sudeb , Woc-Colburn Laila 
Published: October 2019

Abstract

Background
Rickettsia typhi typically causes a nonspecific syndrome characterized by fever, rash, and headache but can rarely progress to severe disease. R. typhi is transmitted by the rat flea and there has been an increased incidence in Houston, TX. Establishing the diagnosis can be challenging and is often made by serological studies. Prompt therapy with doxycycline is important especially in severe disease.

Methods
Karius Test results from the prior 2 years (Redwood City, CA) were reviewed for detections of R. typhi. The Karius Test is a CLIA-certified/CAP-accredited next-generation sequencing (NGS) plasma test that detects microbial cell free DNA (mcfDNA). After mcfDNA is extracted and NGS performed, human sequences are removed and remaining sequences are aligned to a curated pathogen database of >1,000 organisms. Organisms present above a statistical threshold are reported. Chart review was conducted on the cases of R. typhi identified by the Karius Test.

Results
The Karius Test detected R. typhi in 6 adult patients, 4 women and 2 men, from a medical center in Houston, TX. In 2 patients, R. typhi mcfDNA was present in the raw sequencing data but at an abundance below validated statistical thresholds. R. typhi mcfDNA was not found in negative controls run simultaneously with the samples. All patients presented with fever, 4 presented with headache, 3 presented with gastrointestinal symptoms, 3 developed rash, one presented with hypotension. Laboratory data were available for 5 patients. Four patients developed thrombocytopenia, 5 had anemia, 4 patients had WBC < 5, 4 had transaminase elevation and 3 developed hyponatremia. 3 out of 5 had R. typhi serologies sent; all 3 were positive (including two of the patients with R. typhi mcfDNA levels below threshold). In the two other patients the Karius test was the means of establishing the diagnosis. 3 out of 5 patients where data were available were treated with doxycyline.

Conclusion
The Karius test was able to detect R. typhi in a cluster of 6 patients in one medical center in Houston, TX. NGS for mcfDNA offers a rapid means of detecting R. typhi infection. Accurate, rapid diagnosis of R. typhi has important public health implications given its vector-borne mechanism of transmission.

Disclosures
All authors: No reported disclosures.
2170. Xpert Carba-R Assay on Flagged Blood Culture Samples: Clinical Utility in Intensive Care Unit Patients with Gram-Negative Bacteremia
Authors: Rajendran Surendran , Gopalakrishnan Ram , Tarigopula Anil , Dorairajan Sureshkumar , Nambi Panchatcharam Senthur , Sethuraman Nandini , V Ramasubramanian 
Published: October 2019

Abstract

Background
Rapid molecular diagnostics that predict carbapenem resistance (CR) well before the availability of routine drug sensitivity testing (DST) can serve as an antimicrobial stewardship tool in the context of high rates of carbapenem-resistant enterobacteriaceae (CRE).

Methods
A retrospective observational study of patients more than 18 years of age on whom Xpert Carba-R (FDA approved for rectal swab specimen) was done on Gram-negative bacteria (GNB) flagged blood culture samples, in a tertiary care Indian intensive care unit between January 2015 and November 2018.

Results
The study included 160 patients who had a median (Sequential Organ Failure Assessment) SOFA score of 16. A total of 164 GNB were isolated with 4 patients having polymicrobial bacteremia. Klebsiella pneumoniae and Escherichia coli were the predominant isolates (Figure 1). Carba-R was positive in 58/164 (35.36%) samples (Figure 2) and 73/161 isolates (45.34%) were CR (after excluding intrinsic CR organisms) on routine DST. The distribution of CR genes overall was: OXA-48 like (29/58–50%), followed by NDM (19/58–32.7%), followed by OXA-48 and NDM co-expression (9/58–15.51%) and in individual groups as in Figure 3. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value (PPV) and negative predictive value (NPV) of Carba-R vs. routine DST were 90.74%, 93.15%, 13.25, 0.10, 83.58% and 96.31% for enterobacteriaceae (Figure 4). The median time to obtaining the Carba-R report was 30 hours 34 minutes vs. 74 hours and 20 minutes for carbapenem resistance on routine DST. Based on the Carba-R report, 9.72% of patients had escalation of antibiotics (e.g., colistin) to cover CR organisms and 27.08% had de-escalation from CR cover that had already been started.

Conclusion
Xpert Carba-R serves as a rapid diagnostic tool for CR Gram-negative bacteremia, particularly hospital-acquired enterobacteriaceae in intensive care units with a high CRE prevalence. It assists in initiating early appropriate therapy and early institution of infection control measures in these patients, as well as in de-escalation of colistin in patients without carbapenem resistance. We recommend that clinicians consider routinely utilizing this test in this setting.

Disclosures
All authors: No reported disclosures.
2180. Novel Method for Determining Rapid E.coli Antibiotic Susceptibility (AST) Results for Urinary Tract Infections
Authors: Kon Shelley , France Danielle , Walls Fred , Price Connie S 
Published: October 2019

Abstract

Background
Measuring changes in phase noise from bacteria on a quartz crystal resonator has been shown to effectively distinguish viable from non-viable E. coli. We report using this method to rapidly perform AST for E. coli isolated from a leftover clinical urinary tract infection (UTI) specimen.

Methods
An experimental system was designed to sense changes in bacterial mechanics through changes in phase noise generated by bacterial cells (Figure 1). The system includes a quartz-crystal resonator with thin-film gold electrodes on opposite surfaces housed within a module. The module provides electrical contact to the crystal’s electrodes, and incorporates channels through which fluids can be pumped (Figure 2). E. coli was isolated from a leftover positive urine culture specimen, cultured overnight and resuspended in phosphate-buffered saline (PBS). The suspension was run through the experimental system. E.coli cells were adhered to the surface of the quartz resonant crystal coated with a cationic polymer. After a growth phase, the cells were exposed to antibiotic (ampicillin). Phase noise was monitored throughout the test. The power spectral density of the noise was averaged each 5 minutes. E.coli was classified as ampicillin susceptible if the spectral power of the added phase noise was at least 50% lower compared with controls. Controls were in growth media only (Figure 3). Automated microscopy was utilized to monitor cell growth.

Results
The method correctly classified the E.coli as ampicillin susceptible. Power spectral density increased in untreated cells and dropped or stayed steady in cells treated with Ampicillin. Corresponding loss of E. coli viability was confirmed microscopically. Results were compared with standard of care antibiotic susceptibility testing.

Conclusion
The phase noise measurement method correctly identified ampicillin susceptible E.coli isolated from a leftover patient urine sample in three and one half hours. It shows promise for providing rapid AST results to treat UTIs.

Disclosures
All authors: No reported disclosures.
2185. Group A Streptococcus (GAS) Detection by PCR in Children with Viral Acute Respiratory Illness and Healthy Children
Authors: Banerjee Dithi , Crawford Jordan , Harrison Christopher J , Rha Brian , Lively Joana Y , Selvarangan Rangaraj 
Published: October 2019

Abstract

Background
Acute pharyngitis is mostly of viral etiology; GAS, the leading bacterial cause, comprises 20%–30% of pediatric pharyngitis. Patients with pharyngitis and additional acute respiratory illness (ARI) symptoms more suggestive of viral etiology, including cough, rhinorrhea and conjunctivitis, are not recommended for GAS testing. The use of highly sensitive GAS PCR assays in patients with sore throat and viral ARI symptoms may detect GAS colonization and lead to antibiotic overuse. We evaluated GAS PCR in viral ARI inpatients and asymptomatic healthy controls (HC) to illustrate the potential negative impact of offering GAS PCR test in poorly selected patients.

Methods
In November 2015–June 2016, 458 ARI inpatients (< 18 years) and 205 HC (< 5 years, no ARI symptoms within 72 hours) in Kansas City were enrolled in the New Vaccine Surveillance Network study. Mid-turbinate and throat swabs were tested by multiplex respiratory panel PCR and leftover nucleic acid extracts were further tested by real-time GAS PCR. Presenting symptoms of cough, rhinorrhea and/or conjunctivitis, plus sore throat were assessed by parent interview.

Results
Overall, 6.3% of HC < 5 years old and 8.7% of ARI subjects < 18 years were GAS (+); mostly in the 3–15 year old age group (25/40, 62.5%). Among 3–15 year old GAS (+) ARI subjects, 92.8% had cough, 76.2% rhinorrhea and 37.2% conjunctivitis; 80% had > 2 of 3 symptoms noted above. Among 40 GAS (+) ARI subjects, a virus was co-detected in 34 (85%), among which Rhinovirus/Enterovirus were predominant 22/34 (55%). Of the 130 (28%) ARI subjects with sore throat, more tested positive for viruses (107/130, 82.3%) than for GAS (9/130, 6.9%). All GAS (+) HC (13/205, 6.3% overall) were < 3 year olds.

Conclusion
PCR detected GAS in 6.3% HC < 5 years old and 8.7% ARI subjects < 18 years old; mostly in 3- to 15-year-old ARI subjects. Most GAS (+) ARI children had cough, rhinorrhea or conjunctivitis and/or virus co-detection suggesting GAS carriage. Our data demonstrate that GAS may be detected in patients with a low clinical suspicion for acute GAS pharyngitis. These findings highlight the need to review patient selection and exercise caution in implementing highly sensitive GAS PCR assays especially in such clinical settings.

Disclosures
All authors: No reported disclosures.
2202. Validation of a Rabbit Model of Pseudomonas aeruginosa Acute Pneumonia
Authors: Gras Emmanuelle , Vu Trang , Vu Vi Tran Giang , Quynh Nhu Nguyen Tran , Schneider-Smith Erika , Povoa Natalia , Povoa Helvecio , Delaye Thomas , Valour Florent , An Diep Binh 
Published: October 2019

Abstract

Background
Severity and antimicrobial resistance of P. aeruginosa (PA) hospital-acquired pneumonia led the FDA to encourage the development of animal models for preclinical evaluation of new therapeutic strategies. We present here the validation of a rabbit model of PA acute pneumonia.

Methods
Rabbits were infected by endotracheal instillation of 1.8 mL of a standardized inoculum containing 9 × 107 CFU of PA clinical strain 6206 (predetermined 100% lethal dose). The natural history of the disease was described by the following parameters evaluated at 3, 4, 5, 6, 10 hours post-infection (hpi) and at the time of spontaneous death (6 rabbits/group): lung-to-body weight ratio (LW/BW), pulmonary, splenic and renal bacterial counts, pulmonary histology and blood markers (blood cell counts, blood gas and IL-8). Three groups of 12 rabbits were then treated with saline (controls), tobramycin or meropenem at doses determined by PK/PD analysis to confirm the efficacy of a human-equivalent dosing regimen.

Results
PA strain 6,206 caused fatal pneumonia in 13–23 hours by acute respiratory distress syndrome (pulmonary edema and necrosis with LW/BW > 10, pO2 <40 mmHg) and/or sepsis (hyperlactatemia, hypoglycemia, cytopenias). LW/BW and pulmonary bacterial counts increased significantly over time. The splenic and renal bacterial spread was constant after 6 hpi. Hypoxemia <60 mmHg appeared at 5 hpi for 4/6 rabbits, associated with elevated plasma IL-8 concentration, massive neutrophilic influx into the airspace, lung necrosis, hemorrhage, and pulmonary edema formation. Consequently, 5 hpi appeared as the most appropriate time to trigger a therapeutic intervention. Meropenem (80 mg/kg/q2h) or tobramycin (1 injection of 2.5 mg/kg, then saline/q2h) showed superiority over saline, with a mortality rate of 33% and 17% vs. 100%, and an LW/BW ratio of 8.53 and 8.54 vs. 13.9, respectively. Tobramycin was less effective than meropenem in clearing bacteria, with, respectively, 1 and 9 out of 12 rabbits having sterile samples.

Conclusion
This rabbit model of PA acute pneumonia is a reliable evaluation tool for new therapeutic strategies. Our study also provides guidance for the development of animal models by describing the natural history of disease and therapeutic validation.

Disclosures
All authors: No reported disclosures.
2239. Randomized Controlled Trial of a PROcalcitonin-Guided Antibiotic Treatment Algorithm Plus Antibiotic Stewardship the Pediatric Intensive Care Unit (ProPICU)
Authors: Katz Sophie , Crook Jennifer , Gillon Jessica , Szeles Andras , Stanford J Eric , Wang Li , Colby Jennifer , Banerjee Ritu , Banerjee Ritu 
Published: October 2019

Abstract

Background
Procalcitonin (PCT) testing enables earlier antibiotic (abx) de-escalation in adult intensive care units (ICUs); similar data in children are lacking.

Methods
Single-center pragmatic randomized controlled trial of children admitted to the pediatric ICU and started on intravenous (IV) abx February 2018–April 2019 to evaluate whether a PCT-guided testing and treatment algorithm implemented through antibiotic stewardship (AS) audit and feedback promotes abx de-escalation in the pediatric ICU. Patients were randomized by month to either control or PCT arm. Exclusion criteria were receipt of IV abx within 7 days prior to enrollment, immune compromise, neonates < 34 weeks gestation, or receipt of abx for an infection requiring prolonged abx. All subjects had baseline AS review. Subjects in the PCT arm had PCT testing on days 0, 1, 2, and 4 and AS guidance. Some subjects in the control arm had baseline PCT testing that was not available to providers. Abx de-escalation = stopping or narrowing spectrum of abx; Abx escalation = broadening spectrum or starting an additional abx. The primary outcome was abx days of therapy (DOT) per patient in the first 14 days after enrollment. Kruskal–Wallis, Chi-square, and ANOVA tests were used.

Results
The modified intention to treat analysis included 270 patients: 133 control and 137 PCT. Significantly more males and febrile patients were in the PCT-guided arm (Table 1). Overall, abx DOT did not differ between arms (Table 2). In 85 patients with pneumonia, median DOT per patient was shorter in the PCT than control arm (8.0 vs. 9.3 days, P = 0.04). Among patients in the PCT arm, those with initial PCT level > 0.5 mg/L (n = 93) (4.3 vs. 7.1 days, P = 0.006). More AS recommendations (recs) were made in the PCT arm (53 PCT vs. 35 control, P = 0.03). Compliance with AS recs was similar (70%) between arms.

Conclusion
In the pediatric ICU, the use of a PCT testing and treatment algorithm with AS audit and feedback resulted in shorter abx DOT for patients with pneumonia and more AS recs compared with no PCT testing. PCT testing implemented with AS can reduce abx duration in select populations of critically ill children.

Disclosures
Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant.
2257. BDG-Guided Management of Empirical Antifungal Therapy: a Real-life Experience in a Hospital-Wide Context with High Incidence of Non-albicans Candida Infection
Authors: Marconi Lorenzo , Maccaro Angelo , Cimatti Matteo , Scotto Riccardo , Venturelli Claudia , Appolloni Lucia , Furii Francesca , Morotti Marta , Puggioli Cristina , Giannella Maddalena , Viale Pierluigi 
Published: October 2019

Abstract

Background
BDG-guided management of empirical antifungal therapy (AT) has been suggested as a tool to rule out invasive candidiasis (IC) and discontinue AT in critically ill patients. However, some authors reported lower BDG sensibility for non-albicans Candida (NAC) infection. Impact of BDG use in a hospital wide setting has yet to be determined.

Methods
We performed a retrospective observational study of consecutive patients admitted to a 1535-bed teaching hospital from November 2015 to August 2017. Adult patients starting empirical AT and performing at least one BDG test for a suspected fungal infection were included. According to first BDG result and AT management, patients were classified in 3 groups: (G1) negative index BDG and early AT withdrawal; (G2) negative index BDG and AT continued; (G3) positive index BDG and AT continued. IC was defined as monomicrobial Candida spp. isolation from blood cultures and/or surgical specimen. Comparison of the 3 groups was made using post-hoc Bonferroni correction. Univariate and multivariate analyses of risk factors for all-cause 30 days mortality were performed using binary logistic regression model.

Results
Study population consisted of 208 patients, of which 46 (22.1%) were included in G1, 79 (38.0%) in G2, and 83 (39.9%) in G3. NAC species were more commonly isolated from patients with IC and negative BDG (P = 0.005). IC was diagnosed in 2.2%, 13.9%, and 19.3% of G1, G2, and G3, respectively (P < 0.01 for G1 vs. G3). Median AT DDD were 8, 28, and 20 (P < 0.01 for G1 vs. G2 and G1 vs. G3) and 30-day mortality rate was 21.4%, 16.5%, and 30.1%, respectively. Factors associated with 30-day mortality were age, Charlson Comorbidity Index (CCI), ICU admission, SOFA score, septic shock, orotracheal intubation, CVVH and index BDG ≥ 80 pg/mL. At multivariate model, independent risk factors for 30-day mortality were CCI (OR 1.4, 95% CI 1.2–1.6, P < 0.001), SOFA score (OR 1.2, 95% CI 1.1–1.3, P < 0.001) and index BDG≥80 pg/mL (OR 2.4, 95% CI 1.2–4.8, p = 0.012). Model fit was P = 0.65 by Hosmer–Lemeshow test and accuracy according with ROC analysis was 0.82 (95% CI 0.76–0.88).

Conclusion
BDG positivity is a strong predictor of poor outcome, but its accuracy for NAC infection may be suboptimal. Caution may be necessary for AT discontinuation based on a negative BDG result in patients at high risk for NAC infection.

Disclosures
All authors: No reported disclosures.
2262. Ceftazidime–Avibactam vs. Polymyxin B in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae
Authors: John Jamie , Nelson Brian , Macesic Nenad 
Published: October 2019

Abstract

Background
Pharmacotherapy for carbapenem-resistant Enterobacteriaceae (CRE) infections is limited. There is a paucity of evidence to guide optimal management of CRE infections. Ceftazidime–avibactam, a novel cephalosporin/β-lactamase inhibitor, may be a reasonable alternative to colistin for CRE infections, but data on polymyxin B (PB) are lacking. Given the improved pharmacokinetic profile of PB compared with colistin, we sought to evaluate clinical and microbiological outcomes of patients treated with CAZ-AVI vs. PB for CRE infections.

Methods
We conducted retrospective cohort study in adult patients treated with CAZ-AVI or PB for a CRE infection between June 2010 and August 2018. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included clinical cure, microbiological cure, and development of resistance. Endpoints were analyzed using standard statistical measures. The influence of clinical variables other than antimicrobial therapy was assessed in a multivariable regression analysis.

Results
The study included 117 patients, with 42 patients receiving CAZ-AVI and 75 receiving PB. Respiratory and urinary tract infections were most common, occurring in 37.6% and 20.5% of patients, respectively. Bloodstream infections occurred in 45 (35.9%) patients. In the CAZ-AVI group, there were 9 deaths (21.4%), compared with 19 deaths (25.3%) in the PB group (P = 0.653). No statistically significant differences were found in clinical cure or microbiologic cure between CAZ-AVI and PB. PB was associated with a higher incidence of nephrotoxicity (19% vs. 43%; P = 0.048). After adjustment for duration of therapy, combination therapy, and initial WBC, use of PB was not an independent predictor of mortality.

Conclusion
No statistically significant differences between CAZ-AVI and PB were found in clinical or microbiologic outcomes in this cohort of patients treated for CRE infection. Further studies are necessary to confirm these preliminary findings to optimize clinical practice.

Disclosures
All authors: No reported disclosures.