bluuebunny/crossref_metadata_2025 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

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 >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 >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

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

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 (>4 weeks) by the lengths of follow-up intervals, comparing narrow (≤4 weeks) and wide (>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

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

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

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

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

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: >500 pg/mL; range 39 to >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

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.
1168. Role of Extended-Spectrum Cephalosporin-Resistance in Recurrent Enterobacteriaceae Urinary Tract Infections
Authors: Anesi Judith , Lautenbach Ebbing , Nachamkin Irving , Garrigan Charles , Bilker Warren , Omorogbe Jacqueline , Dankwa Lois , Wheeler Mary K , Tolomeo Pam , Han Jennifer ,   CDC Prevention Epicenters
Published: November 2018

Background

Recent data have shown an increase in bacterial resistance to first-line antibiotics used to treat community-onset urinary tract infections (UTIs). A better understanding of the clinical outcomes associated with drug-resistant UTIs in the community is needed. We sought to determine the association between community-onset extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae (EB) UTI and the risk for recurrent UTI.

Methods

A retrospective cohort study was performed. All patients presenting to the Emergency Departments (EDs) or outpatient practices with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed subjects 1:1 on study year. Multivariable Cox proportional hazard regression analyses were performed to evaluate the association between ESC-R EB UTI and time to recurrent UTI within 12 months. Patients were censored at the time of first recurrent UTI or at the end of follow-up.

Results

A total of 302 patients with an index community-onset EB UTI were included, with 151 exposed and unexposed. Within 12 months of the index UTI, 163 (54%) patients experienced a recurrent UTI. The median time to recurrence was 69 days (interquartile range 25–183 days). On multivariable analyses, a UTI due to an ESC-R EB was associated with an increased hazard of recurrent UTI (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.01–1.91, P = 0.04). Other variables that were independently associated with an increased hazard of recurrent UTI included a history of UTI in the 6 months prior to the index UTI (HR 1.59, 95% CI 1.17–2.15, P < 0.01) and presence of a urinary catheter at the time of the index UTI diagnosis (HR 1.59, 95% CI 1.06–2.38, P = 0.03).

Conclusion

Community-onset UTI due to an ESC-R EB organism is associated with a significantly increased hazard of recurrent UTI within 12 months even after adjusting for baseline factors that predispose patients to UTI recurrence. This study raises the question of whether patients with an ESC-R EB organism may require modified treatment regimens. Further study is needed to better elucidate the cause of recurrence among these patients.

Disclosures

All authors: No reported disclosures.
1170. Applying Machine Learning Algorithms to Predict Multi-Drug-Resistant Bacterial Infections From Prior Drug Exposure
Authors: Lendrum Elizabeth , Haslam David , Ambroggio Lilliam
Published: November 2018

Background

Multi-drug-resistant (MDR) infection in the acute care setting prolongs hospital stay and causes high mortality, especially in the pediatric population. Being able to predict MDR infection risk upon or during admission could help prevent and reduce morbidity and mortality in children requiring acute care in the future. This study aimed to develop and validate a predictive model for MDR infection in the pediatric population using machine learning (ML) analysis.

Methods

The study population included hospitalized pediatric patients diagnosed with MDR infection between January 1, 2010 and March 8, 2018. All positive cultures during that period were coded as growing either an MDR or non-MDR organism. ML was performed with random forest (RF) analysis to determine whether hospital drug exposure in the 90 days prior to culture was able to accurately classify cultures as positive for an MDR or non-MDR organism.

Results

During the study period, 7,551 positive cultures were defined as MDR out of a total of 26,913 cultures (28% of all positive cultures). When all cultures were included in the analysis, RF was modestly successful at classifying MDR vs. non-MDR organisms. Significant improvements in classification accuracy were obtained by subdividing cultures based on growth of individual species. RF was able to classify MDR Enterococcus with accuracy = 0.87, positive predictive value of 0.81, and negative predictive value of 0.88. Surprisingly, exposure to many nonantibiotic drugs were important in predicting antibiotic resistance, indicating either that these drugs altered risk directly, or were correlated with MDR risk indirectly.

Conclusion

Drugs without known antimicrobial activity were important predictors of MDR status. Nonantimicrobial drug exposure may be a marker for disease types or therapeutic interventions that place patients at higher risk of MDR infection. Monitoring antimicrobial and nonantimicrobial drug exposure may accurately identify patients at highest risk of MDR infection.

Disclosures

All authors: No reported disclosures.
1175. Clinical and Microbiological Features of Klebsiella pneumoniae Liver Abscess Caused by Multidrug-Resistant Strains
Authors: Lin Yi-Tsung , Cheng Yi-Hsiang , Chuang Chien
Published: November 2018

Background

The endemic Klebsiella pneumoniae liver abscess (KPLA) in East Asian countries are usually caused by hypervirulent strains. These hypervirulent strains are usually susceptible to commonly used antibiotics, aside from their intrinsic resistance to ampicillin. However, hypervirulent K. pneumonaie strains with multidrug-resistant (MDR) phenotype has been reported recently. We aim to investigate clinical and microbiological features of KPLA caused by MDR-resistant strains, and the evolution of drug-resistance in the resistant strain causing recurrent KPLA.

Methods

Patients with KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to February 2018. Capsular genotypes were analyzed in all K. pneumoniae isolates. Antimicrobial-resistant mechanisms were determined for MDR isolates. Pulse-field gel electrophoresis (PFGE), conjugation experiment, and in vivo mice lethality were determined on the strains from a patient with recurrent infection.

Results

During the study period, a total of 211 patients with KPLA, and five patients with recurrence were identified. Most of K. pneumoniae isolates (n = 175, 83.3%) belonged to capsular type K1/K2/K5/K20/K54/K57. Nineteen MDR strains were identified and 15 of them had virulent capsular types (K1 = 7, K2 = 5, K5 = 2, K54 = 1). The major resistance mechanisms of these MDR strains involved the presence of β-lactamases and the overexpression of efflux pumps. The in-hospital mortality of KPLA caused by MDR strains was not significantly higher than wild-type stains (10.53% vs. 4.69%, P = 0.275). In a case with recurrent KPLA, the recurrent capsular type K1 strain (TVGHKP2611) with blaSHV-12 was genetically identical to the primary wild-type resistance strain (TVGHKP2329) by PFGE. The SHV-12-carrying plasmid from TVGHKP2611 was successfully conjugated to Eschericia coli J53. TVGHKP2611 retained high virulence similar to TVGHKP2329 in mice lethality study (median lethal dose < 500 CFU) despite carrying the resistance determinant.

Conclusion

MDR K. pneumoniae strains belonging to virulent capsular types have emerged in KPLA. One SHV-12 producing capsular K1 strain causing recurrent KPLA retained its high virulence, which signals this highly pathogenic and resistant strain could be a major concern in the future.

Disclosures

All authors: No reported disclosures.
1184. Resistance Patterns and Susceptibility Analysis of Klebsiella pneumoniae Infections in Service Members Who Sustained Trauma in Iraq and Afghanistan
Authors: Kiley John , Mende Katrin , Kaiser Susan J , Carson Leigh , Lu Dan Z , Merritt Teresa , Whitman Timothy , Petfield Joseph L , Tribble David R , Blyth Dana M
Published: November 2018

Background

Klebsiella pneumoniae was the third most common species of multidrug-resistant (MDR) Gram-negative organism in military trauma patients injured in Iraq and Afghanistan (2009–2014). This study aims to characterize the antimicrobial susceptibility and resistance patterns of K. pneumoniae isolates in these patients.

Methods

All infecting K. pneumoniae isolates (IKpI) archived by the Trauma Infectious Disease Outcomes Study (TIDOS) and 96 colonizing isolates (CKpI) from groin swabs were included (6/09-12/14). All CKpI linked with IKpI were included; the remainder to total 50 MDR and 46 non-MDR CKpI were chosen randomly. Antimicrobial identification and susceptibilities were determined by CLSI criteria using the BD Phoenix Automated Microbiology System. MDR was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems, and/or fluoroquinolones or production of an ESBL or KPC.

Results

Of 588 K. pneumoniae archived isolates, 237 isolates were included in the analysis (141 IKpI and 96 CKpI). IKpI sources were 40% wound, 22% respiratory, 20% blood, 9% urine, and 9% other. Antibiotic susceptibilities for IKpI were: cefazolin (CFZ) 20%, ceftriaxone 30%, levofloxacin 62%, piperacillin–tazobactam (PTZ) 41%, meropenem 96%, and amikacin 89%. MDR IKpI and CKpI were more likely to have had prior fluoroquinolone (82% vs. 18%, P < 0.01) or anti-pseudomonal penicillin (53% vs. 47%, P < 0.01) exposure. Seventeen patients had CKpI cultured at a median of 5 days (IQR 2–17) before a subsequent IKpI with 11 (65%) having MDR CKpI. All IKpI isolated after MDR CKpI were also MDR. Among IKpI recovered after non-MDR CKpI, new resistance was noted in 1 IKpI to gentamicin (200 days post-CKpI), 1 IKpI to ertapenem (7 days post-CKpI), two IKpI to CFZ (10 days and 17 days, respectively), and 1 IKpI to PTZ (19 days post-CKpI). Serial isolates of IKpI had similar MDR status (63% initial IKpI were MDR, whereas 76% of subsequent IKpI were MDR).

Conclusion

K. pneumoniae isolates in military trauma patients from Iraq and Afghanistan had challenging resistance patterns. Prior exposure to fluoroquinolones and anti-pseudomonal penicillins were associated with MDR K. pneumoniae isolation. MDR status of CKpI predicted subsequent IKpI MDR status.

Disclosures

All authors: No reported disclosures.
1185. Impact of Bloodstream Infections Caused by Multidrug-resistant Organisms on Performance Status: A KARS-Net Study
Authors: Huh Kyungmin , Chung Doo Ryeon , Ko Jae-Hoon , Ha Young Eun , Kim Si-Ho , Oh Suhyun , Jang Sukbin , Mun Seokjun , Huh Hee Jae , Lee Nam Yong , Cho Sun Young , Kang Cheol-In , Peck Kyong Ran , Song Jae-Hoon ,   the Korean Antimicrobial Resistance Surveillance Network (KARS-Net) Investigators
Published: November 2018

Background

Infections caused by multidrug-resistant (MDR) organisms are associated with poorer clinical outcomes and higher economic burden. However, there has been limited data on the impact of MDR infection on the performance status of patients.

Methods

Patients with bloodstream infections by S. aureus, E. faecium, E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii have been identified prospectively as a part of a multicenter nationwide surveillance for antimicrobial resistance. Medical records of the patients enrolled from July 2015 through December 2016 were reviewed for demographic, clinical, microbiologic characteristics, and patient outcome. MDR was defined as MRSA, VRE, and nonsusceptibility to one or more agents in three or more different classes of antibiotics for Gram-negative bacteria. Performance status was evaluated by Eastern Cooperative Oncology Group (ECOG) Performance Status before admission and at discharge. Primary outcome was any decline in ECOG at discharge. Multiple logistic regression was used to identify independent risk factors for ECOG decline.

Results

A total of 19 hospitals participated to the network. The numbers of subjects were 410 for S. aureus, 392 for E. faecium, 708 for E. coli and K. pneumoniae, and 678 for P. aeruginosa and A. baumannii. In univariate analysis, bacteremia by MDR organisms was associated with ECOG decline only in patients with P. aeruginosa (18.4% vs. 10.3%, OR 1.962, 95% CI 1.132–3.399) and A. baumannii (27.6% vs. 11.8%, OR 2.834, 95% CI 1.328–6.045) infections. Patients with MDR K. pneumoniae infection had lower risk of ECOG decline (6.6% vs. 15.8%, OR 0.378, 95% CI 0.183–0.780). Multivariable analysis also showed that infection by MDR organism was independently associated with ECOG decline in patients with P. aeruginosa or A. baumannii infections (OR 2.068, 95% CI 1.478–2.895), but not with other MDR organisms. Comorbidities and initial ECOG showed higher effect size in patients with S. aureus and E. faecium infections.

Conclusion

In this large multicenter nationwide study, bloodstream infections caused by MDR P. aeruginosa and A. baumannii were associated with higher risk of decline in performance status at discharge. MDR status did not show association in infections by other species.

Disclosures

All authors: No reported disclosures.
1204. The MDR Upon Admission Score for Shortening Time to Initiation of Appropriate Antimicrobial Therapy in the Era of Widespread Resistance to Antimicrobials
Authors: Chedid Khalil , Zilberman-Itskovich Shani , Shorbaje Akram , Martin Emily T , Lazarovitch Tsilia , Zaidenstein Ronit , Dadon Mor , Saadon Hodaya , Maya Tal , Marchaim Dror
Published: November 2018

Background

Multi-drug-resistant organisms (MDRO) pose a growing burden, including in non-hospital settings. Delay in initiation of appropriate antimicrobial therapy (DAAT) upon admission to an acute care hospital is common and is associated with worse outcomes. The aim of this study was to develop a prediction score for MDRO infection upon admission, in order to improve patients’ outcomes and avoid misuse of broad-spectrum antimicrobials.

Methods

A retrospective case–control analysis was conducted at Assaf Harofeh Medical Center, Israel, comparing adult patients with MDRO infections diagnosed in the first 48 hours of hospitalization to patients presenting with non-MDRO sepsis (i.e., patients with microbiologically confirmed non-MDRO infection, or patients with non-microbiologically confirmed sepsis). MDROs were determined by clinical laboratory testing. Patients were identified over four consecutive months (August–December 2016). A multivariable logistic regression of predictors for MDRO infection upon admission was used to develop the prediction score.

Results

Ninety-five of 818 total patients (11.6%) had MDRO infection. The final score included 10 parameters: (1) home therapy (IV therapy, wound care, or specialized nursing care, 16 points), (2) routine (at least weekly) outpatient clinic visits in the past 3 months (15 points), (3) history (2 years) of past MDRO colonization (14 points), (4) any antibiotics in the preceding 3 months (12 points), (5) invasive procedure in the past 6 months (11 points), (6) elderly (≥65 years old, 10 points), (7) hemiplegia or paraplegia (8 points), (8) resident of long-term care facility (7 points), (9) severe sepsis (i.e., severe sepsis, septic shock, or multi-organ failure, 6 points), and (10) acute kidney injury (5 points). A cutoff of ≥24 points had a sensitivity of 90%, a specificity of 73% and an ROC AUC = 0.88 (figure).

Conclusion

This study presents the development of a new prediction score for MDRO infection upon admission, based on parameters that could easily be extracted at bedside for patients admitted with sepsis. A future prospective interventional study is needed in order to validate the score, captured at bedside electronically, in terms of improving patients’ outcomes.

Disclosures

All authors: No reported disclosures.
1205. Emergence of Carbapenemase Producing Enterobacteriaceae in South Central Ontario, Canada
Authors: Zhong Zoe , Faheem Amna , Farooqi Lubna , Armstrong Irene , Borgundvaag Emily , Coleman Brenda , Green Karen , Jayasinghe Kithsiri , Johnstone Jennie , Katz Kevin , Kohler Philipp , Li Angel , Melano Roberto , Muller Matthew , Nayani Sarah , Patel Samir , Paterson Aimee , Poutanen Susan , Rebbapragada Anu , Richardson David , Sarabia Alicia , Shafinaz Shumona , Simor Andrew E , Willey Barbara , Wisely Laura , Mcgeer Allison ,   Toronton Invasive Bacterial Diseases Network
Published: November 2018

Background

The spread of CPE is an increasing global threat to patient safety. We describe the introduction and evolution of CPE in south-central Ontario, Canada.

Methods

The Toronto Invasive Bacterial Diseases Network has performed population based surveillance for CPE in metropolitan Toronto and Peel region from first identified isolates in 2007. All laboratories test/refer all carbapenem non-susceptible Enterobacterial isolates for PCR testing for carbapenemases. Demographic and medical data and travel history are collected from chart review and patient/physician interview.

Results

Since 2007, 659 patients have been identified as colonized/infected with CPE; 362, 57%) have at least one clinical isolate. Annual incidence has increased from 0 in 2006 to 1.3 per 100,000 in 2016/17 (Figure 1). First bacteremia occurred in 2010, the incidence in 2017 was 0.14 per 100,000 population. 388 (59%) patients were male, median age was 70 years (range 3 months–100 years). Most common genes among first isolates were NDM (306, 46%), OX48 (149, 23%), KPC (122, 19%). Most common species were K. pneumoniae (268, 41%) and E. coli (259, 39%). Over time, second species/same gene were identified in 113 (16%) patients. In addition, 34/xxx patients with isolates with NDM and/or OXA-48 subsequently had a second isolate with a different gene/gene combination. Of 518 patients whose travel and hospitalization history are available, patients with VIM were less likely than other patients to have a foreign hospitalization or travel history (9/28 vs. 341/490, P < 0.0001). Patients with KPC were more likely to have a hospitalization history outside Canada and the Indian subcontinent (25/70, 36%), in Canada (47/164,29%) than to have no hospitalization in the last year (13/93, 14%), or a history of hospitalization in the Indian subcontinent (2/191, 1%) (P < 0.001). The number of incident patients with different hospitalization and travel history over time is shown in Figure 2.

Conclusion

CPE is increasingly recognized in southern Ontario, both in patients with a history of exposure in healthcare in other countries, and to healthcare in Canada. Intensification of control programs is urgently needed.

Disclosures

S. Poutanen, MERCK: Scientific Advisor, Speaker honorarium. COPAN: Speaker(but not part of a bureau), Travel reimbursement. Accelerate Diagnostics: Investigator, Research support. Bio-Rad: Investigator, Research support. bioMérieux: Investigator, Research support.
1206. Risk Factors of Antibiotic Resistance in E. coli Isolated from the MAL-ED Birth Cohort Study in Rural Tanzania
Authors: Fleece Molly , Nshama Rosemary , Walongo Thomas , Gratz Jean , Platts-Mills James , Mduma Esto , Houpt Eric
Published: November 2018

Background

The emergence and spread of antimicrobial resistance is a serious global public health crisis. Drug-resistant Gram-negative bacteria, like Escherichia coli, are particularly concerning given their significant morbidity and mortality. Despite the increasing prevalence of drug-resistant Gram-negative bacteria worldwide, there are significant knowledge gaps in low resource countries. We aimed to characterize the prevalence, phenotypes, and risk factors of drug-resistant E. coli carriage in children up to age 5 from stool collected in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study in rural Tanzania.

Methods

Two hundred sixty-two children were enrolled in the MAL-ED Tanzania site. We randomly selected 100 children who had E. coli specimens archived every 6 months through 60 months. Up to five lactose-fermenting colonies were selected from growth on MacConkey agar. Drug susceptibility testing of 18 antibiotics was performed by disk diffusion. CLSI interpretive criteria were used for determination of resistance. Generalized estimating equations were used to create a multivariate Poisson regression model for drug resistance risk factors.

Results

Eight hundred twenty-three E. coli specimens were available for testing. The highest rates of resistance were to ampicillin, cefazolin, and cotrimoxazole, respectively. No carbapenem resistance was found. 1.8% met criteria for extended-spectrum β-lactamase production based on combination disk testing. 696 (84.6%) specimens met criteria for multi-drug resistance (nonsusceptible to at least 1 drug in at least three drug categories). In terms of dynamic risk factors, there was no association between antibiotic use or episodes of diarrhea and antibiotic resistance. For static risk factors, there was an association between higher income and increased antibiotic resistance.

Conclusion

Antibiotic resistance carriage is an under recognized problem in this setting. Resistance rates at 6 months of age are higher than expected, with surprisingly little variance explained by individual-level risk factors for resistance in this community.

Disclosures

All authors: No reported disclosures.
1209. Expanding an Economic Evaluation of the Veterans Affairs Initiative to Prevent Methicillin-Resistant Staphylococcus aureus Infections to Include Prevention of Gram-Negative Bacteria
Authors: Nelson Richard E , Goto Michihiko , Samore Matthew , Jones Makoto , Stevens Vanessa , Evans Martin , Schweizer Marin , Perencevich Eli , Rubin Michael
Published: November 2018

Background

In October 2007, the Department of Veterans Affairs (VA) launched the National MRSA Prevention Initiative, a nationwide effort to reduce MRSA transmission through (1) universal screening, (2) contact isolation for MRSA+ patients, (3) institutional culture change that “infection prevention is everyone’s business,” (4) emphasis on hand hygiene, and (5) increased infection control resources. While the initiative focused on MRSA, recent evidence suggests that it also led to a significant decrease in hospital-onset (HO) Gram-negative rod (GNR) bacteremia. The objective of this analysis was to evaluate the cost-effectiveness and the budget impact of the initiative taking into account both MRSA and GNR infections.

Methods

We developed an economic model using published data on the rate of MRSA HAIs and HO-GNR bacteremia in the VA from October 2007 to September 2015, estimates of the attributable cost and mortality of these infections, and the costs associated with the intervention obtained through a microcosting approach. We explored several different assumptions for the rate of infections that would have occurred if the initiative had not been implemented. Effectiveness was measured in life-years (LYs) gained.

Results

We found that during fiscal years 2008–2015, the initiative resulted in an estimated 4,761–9,236 fewer MRSA HAIs and 1,447–2,159 fewer HO-GNR bacteremia. The initiative itself was estimated to cost $206 million over this 8-year period while the cost savings from prevented MRSA HAIs ranged from $75–165 million and from prevented HO-GNR bacteremia ranged from $42–62 million. The incremental cost-effectiveness of the initiative ranged from $12,146–$46,500/LY when just including MRSA HAIs and from $7,945–$24,387/LY when including HO-GNR bacteremia. The overall impact on the VA’s budget ranged from $200–$334 million.

Conclusion

An MRSA surveillance and prevention strategy in VA may have prevented a substantial number of MRSA and GNR infections. The savings associated with the prevented infections helped to offset some but not all of the cost of the initiative. Economic evaluations of these interventions can help decision makers understand the trade offs between increased cost and improved health that can come from such interventions.

Disclosures

All authors: No reported disclosures.