bluuebunny/crossref_metadata_2025_split huggingface dataset:
1764. The Gut: A Veiled Reservoir for Multidrug-resistant Organisms (MDROs) Below the Tip of the Iceberg
Authors: Shimasaki Teppei , Rhee Yoona , Yelin Rachel D , Ariston Michelle , Ollison Stefanie , Fogg Louis , Dangana Thelma , Cisneros Enrique Cornejo , Weinstein Robert A , Lolans Karen , Schoeny Michael , Lin Michael Y , Moore Nicholas M , Hayden Mary K ,   The CDC Prevention Epicenters Program
Published: November 2018

Abstract

Background
Clinical culture results are sometimes used to estimate the burden of multidrug-resistant organisms (MDROs) in hospitals. The association between positive clinical culture results and prevalence of MDROs in the gut is incompletely understood.

Methods
Rectal swab or stool samples were collected daily from adult medical intensive care unit (MICU) patients and cultured for target MDROs using selective media between January 2017 and January 2018 at Rush University Medical Center, a 676-bed tertiary-care center in Chicago. Resistance mechanisms were confirmed by phenotypic methods and/or polymerase chain reaction. Clinical culture results during MICU stay were extracted from the hospital information system. Target MDROs included vancomycin-resistant Enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB). Patients with either a study or clinical culture positive for a target MDRO were analyzed.

Results
We collected 5,086 study samples from 1,661 unique admissions (1,419 patients) and included here data from 413 unique admissions (397 patients) with completed microbiologic analysis. Median (IQR) patient age was 65 (51–75) years and length of MICU stay was 3 (3–4) days. A total of 156 (37.8%) patients had a target MDRO detected from a study sample at any point; 57 (36.5%) patients had &gt;1 MDRO detected. Overall prevalence of these MDROs was found to be 22.5% VRE, 6.5% CRE, 19.8% ESBL, 4.4% CRPA, and 0.7% CRAB. New MDRO acquisition was observed in 58 (14.6%) patients (figure). Once a target MDRO was detected in a study sample, 82.2% of subsequent study samples were positive for that MDRO. Only 13 (5.8%) patients had a positive clinical culture for any target MDRO during their MICU stay (table).

Conclusion
Clinical cultures capture only the tip of the resistance iceberg and alone are insufficient to guide MDRO-targeted prevention strategies. Universal infection prevention measures are an alternative that may be preferred in settings where overall prevalence of MDROs is moderate or high and patients may be colonized with &gt;1 MDRO.

Disclosures
All authors: No reported disclosures.
1765. Use of a Natural Language Processing-Based Informatics Pipeline for Infectious Disease Syndrome Surveillance
Authors: Zachariah Philip , Hill-Ricciuti Alexandra , Natarajan Karthik 
Published: November 2018

Abstract

Background
Automated surveillance for infectious disease syndromes (IDS) in hospitals mostly relies on structured data (e.g., diagnosis codes). Natural language processing (NLP) enables screening and concept extraction from large repositories of unstructured data (e.g., clinician notes). We demonstrate the use of an NLP-based pipeline to improve case finding for a specific IDS (urinary tract infection [UTI]) and compare this to surveillance using ICD-10 codes.

Methods
Inpatient hospitalizations in 2016 with ICD-10 codes for UTI at a children’s hospital were identified. Records of inpatients with positive urine cultures for 2016 were reviewed to identify missed cases. Notes for inpatient hospitalizations for 2016 were processed using an NLP pipeline. The NLP pipeline receives real-time data, accounts for institution-specific document structure, performs named-entity recognition on clinical problems/symptoms, and matches these terms to concept unique identifiers (CUI) in the unified medical language system (UMLS). We used the UMLS CUI for urinary tract infections (C0042029) to identify notes of interest. To minimize false positives, we selected as the threshold for case positivity—the mean UTI CUI mentions per patient during 2016.

Results
Among 10,681 hospitalized patients, there were 181 unique patients that were identified with UTI using ICD-10 codes. An additional 85 UTI cases were identified using chart review of positive urine cultures (n = 409). A total of 289,344 notes were screened by the NLP pipeline to identify UTI patients. Using the predefined threshold (n = 6), all cases of UTI identified by ICD-10 screening were detected by the NLP-based method. Of the additional cases missed by ICD-10 codes, 84 of 85 (98.9%) were positive by the NLP-based method. To identify these 84 true cases, an additional 275 charts without UTI, flagged as positive by the NLP method, would have to be reviewed (ratio of ~1:3).

Conclusion
We demonstrate the use of an NLP-based pipeline to enhance IDS surveillance. Using NLP-based surveillance with other methods could facilitate case detection and outbreak control for IDS that lack microbiologic data or have novel presentations. Further work will improve the specificity of NLP-based case finding methods and apply this to other IDS.

Disclosures
All authors: No reported disclosures.
1767. Structured Treatment Interruptions in HIV-Infected Patients Receiving Antiretroviral Therapy—Implications for Future HIV Cure Trials: A Systematic Review and Meta-analysis
Authors: Stecher Melanie , Löhnert Annika Y , Klein Florian , Lehmann Clara , Wyen Christoph , Fätkenheuer Gerd , Vehreschild Janne 
Published: November 2018

Abstract

Background
Safety and tolerability of analytical treatment interruption (TI) as part of HIV cure studies has been discussed controversially. In this systematic review and meta-analysis, we report current evidence for the occurrence of adverse effects during different types of TI.

Methods
A systematic literature search on studies reporting on TIs was conducted using a defined search term, covering the period from January 1988 to May 2017. All interventional and observational studies were reviewed, and results were extracted based on predefined criteria. We evaluated the proportion of adverse effects during TI by using a random effect meta-analysis model. A meta-regression model was calculated to explore the variation across studies and the influence of key factors.

Results
We identified 1,048 studies, of which we obtained data from 24 studies investigating TI including 7,961 individuals. Sample sizes varied from 6 to 5,472 subjects. The number of reported events during TI ranged from 0 to 241. Follow-up intervals during TI varied from 2 days up to 3 months. We compared reported adverse effects in studies with long TI (&gt;4 weeks) by the lengths of follow-up intervals, comparing narrow (≤4 weeks) and wide (&gt;4 weeks) follow-up during TI. The proportion of patients exhibiting adverse events during long TI was 1% (95% CI 0–4, I2 = 24.9%) in studies with narrow and 10% (95% CI 5–117, I2 = 95.1%) in studies with wide follow-up intervals, with an overall reported rate of 5% (95% CI: 3–15, z = 3.93, P ≤ 0.00) (Figure 1). The number of reported deaths was relatively low, but higher in studies with wide follow-up compared with studies with narrow follow-up (Figure 2). Meta regression analysis indicated that adverse events were increasing with the length of the monitoring interval (β = 0.75, 95% CI 0.24–1.27, P = 0.007) (Figure 3).

Conclusion
Current evidence indicates that studies with narrow follow-up intervals did not show a substantial increase of adverse effects other than viral rebound during TI. Analytical treatment interruption may be a safe strategy as part of HIV cure trials if patients undergo intense follow-up routines.

Disclosures
All authors: No reported disclosures.
1772. Vancomycin-Resistant Enterococcus Alters the Gastrointestinal Microbiome in Critically Ill Patients
Authors: Cuaresma Edward , Laszkowska Monica , Stump Stephania , Moscoso Dagmara , Chong David , Freedberg Daniel 
Published: November 2018

Abstract

Background
In critically ill patients, rectal colonization with VRE is associated with an increased risk for nosocomial infection or death. In mice, fecal transplantation of Blautia producta directly inhibits VRE growth and leads to clearance of VRE. We performed a prospective, intensive care unit (ICU)-based study to evaluate the relationship between B. producta and VRE. We also sought to determine the relationship between VRE, MRSA, and other common MDR bacteria.

Methods
This study included 97 adults newly admitted to the ICU between February 2015 and June 2016. Rectal swabs were obtained at time of ICU admission and 72 hours later. VRE rectal colonization status was determined categorically for each sample by culture on selective media. Specimens were also cultured for methicillin-resistant Staphylococcus aureus (MRSA) and for MDR Gram-negatives, defined as those with nonsusceptibility to 3 or more antibiotic classes. 16S rRNA gene sequencing was performed and the relative abundance was calculated for B. producta. Differentially abundant bacteria taxa between VRE positive and VRE negative specimens were assessed using linear discriminant analysis effect size (LefSe) analysis.

Results
Among the 97 patients, 7 (7.2%) were colonized with VRE at the time of ICU admission and 3 (3.3%) of the remaining patients became colonized 72 hours later. The microbiome composition differed significantly when accounting for VRE colonization status. The relative abundance of B. producta was 140-fold higher in VRE-negative compared with VRE-positive samples (0.0012% vs. 8.48 × 10–6%, P = 0.03). On LefSe analysis, there was also significantly lower differential abundance of B. producta when VRE was present (LDA score 4.65). The presence of VRE in culture was significantly associated with the co-presence of MRSA (23.5% co-colonized if VRE positive vs. 8.4% if VRE negative, P = 0.046) but not with the copresence of MDR Gram-negative bacteria (29.4% if cocolonized if VRE positive vs. 34.3% if VRE negative, P = 0.68).

Conclusion
In this ICU cohort, rectal colonization with VRE was inversely associated with the putatively protective organism B. producta. VRE was associated with rectal co-colonization with MRSA but not with MDR Gram-negative bacteria. B. producta may have promise as a probiotic designed to prevent VRE colonization.

Disclosures
All authors: No reported disclosures.
2562. Re-Appraisal of Aminoglycoside (AG) Susceptibility Testing Breakpoints Based on the Application of Pharmacokinetics–Pharmacodynamics (PK-PD) and Contemporary Microbiology Surveillance Data
Authors: Bhavnani Sujata M , Onufrak Nikolas J , Hammel Jeffrey P , Andes David R , Bradley John S , Flamm Robert K , Ambrose Paul G , Jones Ronald N 
Published: November 2018

Abstract

Background
Resistance to AGs and numerous other classes continues to emerge. To ensure that susceptibility is accurately characterized and that clinicians have reliable data to select effective agents, appropriate in vitro susceptibility testing interpretive criteria (susceptible breakpoints [BKPTs]) are crucial to ensure optimal patient care. Recently, USCAST, the USA voice to EUCAST/EMA, evaluated the BKPTs for the 3 most commonly used AGs, gentamicin, tobramycin, and amikacin [Bhavnani et al., IDWeek 2016; P-1977]. As a result of consultation from interested parties, which included evaluating AG dosing regimens provided in the US-FDA product package inserts and simulated patients with varying creatinine clearance, these BKPTS were reassessed.

Methods
Data sources considered included longitudinal US reference MIC distributions using in vitro surveillance data collected over 18 years, QC performance (MIC, disk diffusion), population pharmacokinetics (PK), and in vivo PK-PD models. Using population PK models, PK-PD targets for efficacy and Monte Carlo simulation, percent probabilities of PK-PD target attainment by MIC after administration of traditional and extended interval AG dosing regimens were evaluated among simulated patients. Epidemiological cut-off and PK-PD BKPTs were considered when recommending BKPTs for AG–pathogen pairs.

Results
An example of PK-PD target attainment analysis output is provided in Figure 1 and a subset of recommended AG BKPTs for 3 pathogens is shown in Table 1. Updated USCAST BKPTs, which were based on the application of population PK and PK-PD models, simulation techniques, and contemporary MIC distribution statistics, are generally lower than those of EUCAST/EMA, USA-FDA, and CLSI. Adequate PK-PD target attainment was not achieved for some AG-pathogen pairs, even when high-dose AG dosing regimens and PK-PD targets for stasis were evaluated (e.g., gentamicin vs. P. aeruginosa; amikacin vs. S. aureus).

Conclusion
These revised AG BKPT recommendations, which will be made freely available to EUCAST, USA-FDA, and CLSI, will be finalized after considering comments from additional interested stakeholders. This process will be followed in an effort to bring harmonization to global BKPTs for AGs.

Disclosures
All authors: No reported disclosures.
2563. Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Meningitis and Encephalitis
Authors: Wilson Michael , Sample Hannah , Zorn Kelsey , Naccache Samia N , Miller Steve , Chiu Charles Y 
Published: November 2018

Abstract

Background
Metagenomic next-generation sequencing (mNGS) of CSF can identify nearly all pathogens in a single test. We previously validated a CSF mNGS assay in a licensed clinical laboratory. To date, the utility of mNGS for infectious disease diagnosis has been described in case reports and small case series, but not in a large-scale clinical trial.

Methods
The PDAID (“Precision Diagnosis of Acute Infectious Diseases”) study was a 1-year nationwide prospective study across 8 tertiary care hospitals to evaluate the performance and utility of a clinical metagenomic sequencing assay for diagnosis of meningitis, encephalitis, or myelitis from cerebrospinal fluid (CSF) (ClinicalTrials.gov number NCT02910037). We recruited acutely ill hospitalized inpatients lacking a diagnosis at the time of enrollment. CSF samples were processed and analyzed by mNGS testing within 1 week of receipt in the clinical microbiology laboratory, with sequencing results reported in the patient medical record and used to make contemporaneous treatment decisions. Weekly clinical microbial sequencing boards were convened to discuss mNGS results with treating physicians, and clinical impact evaluated by surveys, chart review, and direct clinician feedback.

Results
A total of 204 patients were enrolled. Patients were severely ill (ICU 48%, average length of stay 26 days, overall 30-day mortality 7.4%). Fifty-nine neurologic infections were diagnosed in 57 patients (27.9%). mNGS identified 15 (25.4%) infections that were missed by all conventional microbiological tests, including emerging and/or uncommon pathogens such as St. Louis encephalitis virus, hepatitis E virus acquired by lung transplant, and Nocardia farcinica. Twelve of the 15 mNGS-only diagnoses (80%) had clinical impact, with 9 of 15 (60%) guiding appropriate treatment. For diagnosis of infections by direct detection CSF testing, mNGS had 79.1% sensitivity and 98.8% specificity, versus 65.1% sensitivity and 99.4% specificity by conventional testing.

Conclusion
A significant proportion of neurologic infections are missed despite extensive diagnostic testing performed in tertiary care hospitals. Clinical metagenomic CSF testing was found to be useful in increasing the number of diagnosed neurologic infections and providing actionable information for physicians.

Disclosures
All authors: No reported disclosures.
2564. Clinical Validation of a Commercial LAMP Test for Ruling Out Malaria in Returning Travelers: A Prospective Diagnostic Trial
Authors: Cheaveau James , Nguyen Hong , Chow Barbara , Zhou Hong Yuan , Mohon Abu Naser , Viana Giselle , Chan Wilson W , Pillai Dylan 
Published: November 2018

Abstract

Background
The mainstay of malaria diagnosis relies on rapid diagnostic tests (RDT) and Giemsa-stained microscopy both of which lack analytical sensitivity. This leads to repeat testing to rule out malaria. Nucleic acid amplification (NAT) methods are more sensitive, but testing requires technical proficiency beyond the average clinical laboratory.

Methods
We conducted a prospective diagnostic trial of the Meridian illumigene Malaria assay (LAMP) compared with reference microscopy and RDT (BinaxNOW Malaria) in returning travelers in Western Canada between June 2017 and January 2018. Returning travelers with signs and symptoms of fever were enrolled into the study. RDT, microscopy, and LAMP assays were performed simultaneously. To increase the yield of positive specimens for all species of malaria, retrospective specimens of Plasmodium vivax, P. ovale, and P. malariae species were supplemented. Real-time (RT)–PCR testing was performed on all specimens to resolve discrepancies. A cost–benefit analysis was performed.

Results
A total of 296 consecutive patients (50.7% male, mean age 32.5) were enrolled, most visiting friends and relatives (43.2%), traveling to Asia (48.4%), presenting with fever (88.9%), not taking prophylaxis (82.8%), and treated as outpatients (84.3%). In the prospective arm, LAMP had a sensitivity of 98.1% (95% CI 89.9–99.9) and a specificity of 97.6% (95% CI 95.2–99.0) versus microscopy. After discrepant resolution with RTPCR, LAMP had a sensitivity of 100% (95% CI 93.9–100) and a specificity of 100% (95% CI 98.7–100) versus microscopy. When including retrospective specimens, LAMP had a sensitivity of 98.7% (95% CI 92.7–99.9) and a specificity of 97.6% (95% CI 95.2–99.1) versus microscopy, and after discrepant resolution of this set, LAMP had a sensitivity of 100% (95% CI 95.5–100) and a specificity of 100% (95% CI 98.7–100). The rate of invalid tests with LAMP was 3.05%. After discrepant resolution, RDT had a sensitivity of 83.3% (95% CI 58.6–96.4) and a specificity of 96.2% (95% CI 93.2–98.1) versus microscopy. A cost–benefit analysis of reagents and labor suggests up to USD 13 savings per specimen using a revised algorithm with LAMP screening.

Conclusion
A novel, highly sensitive testing algorithm for malaria screening with associated cost savings in the nonendemic setting is proposed.

Disclosures
D. Pillai, Meridian Biosciences: None, Diagnostic testing material for study.
2566. Diagnosis of Pneumocystis jiroveci Pneumonia in HIV-Negative Immunocompromised Patients: Is the Gomori-Methenamine Silver Stain of Bronchoalveolar Lavage Fluid the Gold Standard or Sub-Standard?
Authors: Slotkin Rebecca , Abi-Raad Rita , Liu Yuehong , Grant Matthew , Malinis Maricar , Azar Marwan M 
Published: November 2018

Abstract

Background
Direct visualization of Pneumocystis jiroveci on bronchoalveolar lavage (BAL) fluid using the Gomori-methenamine-silver (GMS) stain historically has been the mainstay of diagnosis for P. jiroveci pneumonia (PJP), with studies from the early HIV/AIDS era reporting sensitivities of 90–95%. However, the burden of P. jiroveci organisms in BAL fluid is significantly lower in HIV-negative immunocompromised patients compared with HIV-positive patients with PJP, raising concerns that the BAL GMS stain is less sensitive in this population.

Methods
We conducted a retrospective observational study at Yale-New Haven Hospital from 2012 to 2018, using electronic medical record chart reviews, to identify patients who underwent bronchoscopy with BAL GMS stain for the diagnosis of PJP. We collected additional patient factors such as age, sex, HIV status, and immunosuppressed status. For patients with a negative BAL GMS stain, we collected data on other diagnostics, including positive GMS lung biopsies, positive PJP PCR or DFA, and elevated serum (1–3)-β-d-glucan levels. We defined BAL GMS-negative cases as proven or probable based on investigator generated criteria (see Figure 1).

Results
We identified 52 patients with PJP who received a BAL GMS stain, including 28 HIV-positive and 24 HIV-negative cases. Of 24 HIV-negative cases, 11 had BAL GMS-positive PJP and 13 had BAL GMS-negative PJP (9 proven and 4 probable). In the latter group, 6 had hematologic malignancies (HM), 2 had solid-organ transplants (SOT), 1 had hematopoietic stem cell transplant, 2 had SOT plus HM, and 2 received high-dose steroids. Proven diagnoses were made by GMS-positive lung biopsy (n = 6), DFA (n = 2), and PCR (n = 1). Elevated (1–3)-β-d-glucan was observed in 7 of 8 cases (median: &gt;500 pg/mL; range 39 to &gt;500). Three patients developed adverse outcomes (1 readmission due to untreated PJP and 2 treatment delays). BAL GMS sensitivity for HIV-negative patients was 11/24 (46%) vs. 28/28 (100%) in HIV-positive patients.

Conclusion
The sensitivity of BAL GMS for PJP is poor in HIV-negative immunocompromised patients. Missed cases or delayed treatment for PJP may lead to adverse outcomes. In HIV-negative patients with a clinical syndrome compatible with PJP, a negative BAL GMS does not rule out PJP and must be confirmed by supplementary diagnostics.

Disclosures
All authors: No reported disclosures.
1167. Trends in Multi-Drug-Resistant Gonorrhea, Gonococcal Isolate Surveillance Project, United States, 1987–2016
Authors: St. Cyr Sancta , Kersh Ellen , Weinstock Hillard , Torrone Elizabeth 
Published: November 2018

Abstract

Background
Neisseria gonorrhoeae’s ability to develop resistance to antibiotics used for treatment and a limited development of new therapies have made this organism one of three urgent threat pathogens in the United States. We provide the first report of US trends in multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) gonorrhea.

Methods
The Gonococcal Isolate Surveillance Project (GISP) monitors trends in antimicrobial susceptibility in N. gonorrhoeae in the United States. Antimicrobial susceptibility testing by agar dilution is performed on urethral isolates from male patients at participating STD clinics. Minimum inhibitory concentration (MIC) are used to identify isolates with resistance or reduced susceptibility using the following criteria: fluoroquinolones (ciprofloxacin [MIC ≥1.0 μg/mL]) and elevated MICs to cephalosporins (cefixime [MIC ≥0.25 μg/mL], ceftriaxone [MIC ≥0.25 μg/mL]) and macrolides (azithromycin [MIC ≥1.0 μg/mL before 2005 and ≥2.0 μg/mL 2005–2016]). In this analysis, MDR is defined as resistance or elevated MICs to ≥2 classes of antimicrobials; XDR as resistance or elevated MICs to ≥3 classes. This classification excludes penicillin and tetracycline due to their long history and high prevalence of gonococcal resistance.

Results
During 1987–2016, 159,445 isolates were collected through GISP. In 1998, the first MDR strains were identified. Although only 0.04% of isolates that year, these isolates showed elevated MICs to both cephalosporins and macrolides. By 2010, 1.0% of GISP isolates were MDR with elevated MICs or resistance to two of the cephalosporins, macrolides, or fluoroquinolones. In 2011, the proportion of isolates that were MDR peaked at 1.3%. In 2016, after minor fluctuations, 1.1% of GISP isolates were considered MDR. Only one occurrence of XDR, in 2011, has been seen in GISP. The strain was resistant to fluoroquinolones with elevated MICs to both cephalosporins and macrolides.

Conclusion
MDR and XDR gonorrhea have remained low over the past three decades; however, dual treatment with cephalosporins and macrolides is the last remaining recommended therapy for N. gonorrhoeae. Until new treatment options become available, a combination of surveillance and ensuring appropriate treatment are needed to delay further resistance.

Disclosures
All authors: No reported disclosures.