bluuebunny/crossref_metadata_2025 huggingface dataset:
2149. Performance of a Gradient Diffusion Method (Etest®) on Mueller–Hinton Agar with Sheep Blood for Aerococcus urinae Antimicrobial Susceptibility Testing
Authors: Berteau Tammy , Emilie Roy France , Bestman-Smith Julie , Grandjean-Lapierre Simon , Longtin Jean , Dufresne Simon-Frédéric , Domingo Marc-Christian , Leduc Jean-Michel
Published: October 2019

Background

Aerococcus urinae is frequently identified by MALDI-TOF in urinary specimens. It is generally susceptible to β-lactams, but its susceptibility pattern to fluoroquinolones (FQ) remains unpredictable. The goal of this study was to evaluate the performance of the gradient diffusion method (Etest®) to determine FQ susceptibility compared with broth microdilution (BMD) and agar dilution (AD).

Methods

Prospectively collected isolates of A. urinae from urinary tract specimens originating from 5 hospitals in Quebec city and Montreal were identified by MALDI-TOF (Vitek-MS). All isolates were tested using BMD according to CLSI guidelines, and also with Etest® strips on MH agar w/ 5% sheep blood. Isolates showing trailing, insufficient growth or discordance between both methods were further tested by agar dilution (MH agar w/5% horse blood + β-NAD) according to EUCAST guidelines. Breakpoints were interpreted using CLSI M45-A3. Combined results of BMD and AD were then compared with Etest.

Results

Of the 207 isolates of A. urinae tested, 37 showed trailing (17,8%) and 19 (9,2%) insufficient growth with the BMD method and were retested using AD. Moreover, 38 isolates (ciprofloxacin) and 13 isolates (levofloxacin) showed either lack of categorical or essential agreement between Etest and BMD and were also retested using AD to arbitrate discrepancies. Susceptibility profiles combining BMD and AD are presented in Table 1. As suggested in EUCAST guidelines, readings were much clearer and growth was better with AD compared with BMD. The categorical agreement of the Etest® with BMD+AD was 95% for ciprofloxacin and 97% for levofloxacin. Essential agreement was 95% for ciprofloxacin and 97% for levofloxacin. No very major errors were identified. Two major errors were identified for levofloxacin (1,2%) and one for ciprofloxacin (0.6%).

Conclusion

Gradient diffusion method using Etest® strips on MH agar w/ sheep blood is a valid method to determine susceptibility to FQ for urinary tract isolates. As a reference method, AD provides clearer endpoints and better growth than BMD for FQ susceptibility testing.

Disclosures

All authors: No reported disclosures.
2152. Detection of Uropathogens Using BD Kiestra™ Total Laboratory Automation with Urine Culture Application
Authors: Patel Parul , Droske Lauren E , Patel Jignesh , Barza Ruby , Lindgren Rebecca , McElvania Erin
Published: October 2019

Background

Urine is the most frequently cultured specimen type for the majority of clinical microbiology laboratories. Typically, around 30% of cultures are positive for uropathogens with 70% yielding insignificant or mixed growth. BD is developing a software Urine Culture Application (UCA) for the BD Kiestra Total Laboratory Automation (TLA) system to screen images of urine culture plates, sort them based on growth vs. insignificant growth and also allow for presumptive pathogen identification.

Methods

De-identified urine specimens were inoculated onto BD BBL™ CHROMagar™ Orientation Media (CHROM; BD, Sparks, MD), CHROM/Trypticase™ Soy Agar II with 5% Sheep Blood (TSA) biplate, BD BBL MacConkey II agar, and TSA using the BD Kiestra TLA system. Plates were imaged at 24 hours using the BD Kiestra™ ReadA Compact imaging acquisition software and an algorithm was applied to the images using the UCA (Version 2.0). Semi-quantitative measurements of <100, 100–1,000, 1,000–10,000, 10,000–100,000, and >100,000 cfu/mL growth were determined by UCA for all media types and presumptive ID was determined using CHROM. Manual reading of the images by two technologists was the gold standard for comparison. For discrepant results, a third manual reader was used as an arbitrator.

Results

Testing between 877 and 934 urine specimens on each of five media types using UCA resulted in an exact semi-quantitative agreement with manual reading for 85.5–95.0% of specimens (Table 1). If semi-quantitative values ± one category of agreement are included, the number rises to 98.2–99.4% agreement. Using CHROM for presumptive identification of pure or predominant organisms, UCA was in agreement with manual identification in 251 of 272 cultures (92.3%). Of the 21 discrepant organisms, 19 were classified as “other” by manual reading but were identified as specific organisms by UCA. Definitive organism identification was not performed.

Conclusion

UCA was able to accurately categorize bacterial growth into five semi-quantitative categories using five media types. Pure and predominant uropathogens were accurately identified from CHROM using UCA. The use of UCA software application may enable laboratories to save time screening urine cultures by allowing more efficient use of technologist time.

Disclosures

All authors: No reported disclosures.
2155. Accelerated Confirmation of Porin Loss in Carbapenem-Resistant Enterobacterales: A MALDI-TOF Mass Spectrometry-Based Approach
Authors: Correa-Martinez Carlos , Idelevich Evgeny A , Becker Karsten
Published: October 2019

Background

The accurate identification of carbapenem resistance mechanisms is decisive for the appropriate selection of antibiotic regimens. Numerous methods can detect carbapenemase-producing carbapenem-resistant bacteria (CPCR). However, non-CPCR (NCPCR) are routinely assumed to display porin loss as a diagnosis of exclusion. No further confirmatory tests are performed since the gold standard (sodium dodecylsulfate polyacrylamide gel electrophoresis, SDS–PAGE) is laborious and time consuming. We propose a test for rapid and easy detection of porin loss by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Methods

Clinical meropenem-resistant Enterobacterales strains (10 CPCR, 10 NCPCR) and control strains recommended by EUCAST (5 carbapenemase-producing, one with porin loss, one-negative control) were analyzed. Membrane proteins were extracted by successive centrifugation of bacterial suspensions (McFarland 0.5) and addition of ethanol, formic acid and acetonitrile. MALDI-TOF MS of the protein extracts was performed on a 96-spot target (Bruker Daltonics, Germany). Peaks between 35 and 40 kDa were analyzed for the presence of porins and compared with the bands observed in the SDS–PAGE of the protein extracts.

Results

Within the molecular weight range of 35–40 kDa, the MALDI-TOF MS-based method revealed peaks in all CPCR isolates corresponding to those observed in the carbapenemase-producing control strains. In contrast, the control strain with porin loss as well as all CNCR isolates showed a lower quantity of peaks in this range. All peaks observed correlated with the bands observed in the SDS–PAGE of the protein extracts at the corresponding molecular weight (Figure 1).

Conclusion

Yielding results that reliably correspond to the current gold standard, we propose a method for accelerated detection of porin loss as an alternative to the diagnosis of exclusion usually made in routine settings. With a processing time of approximately 20 minutes, the method can be easily implemented in the clinical setting. Applying this MALDI-TOF MS-based approach, valuable information will be provided about a resistance mechanism that otherwise remains unexplained.

Disclosures

All authors: No reported disclosures.
2169. An Algorithm-Based Approach Reduces Overuse of Meningitis/Encephalitis Multiplex PCR Panel
Authors: Gitman Melissa R , Nowak Michael D , Navis Allison , Mia. Sordillo Emilia
Published: October 2019

Background

Syndromic molecular panels enable rapid diagnosis and optimized management of infections with significant morbidity and mortality, but may be overused without clear guidelines. A recent report indicated there was little clinical suspicion of infection in up to 1/3 of cases for which a FILMARRAY® Meningitis/Encephalitis Panel (ME Panel, bioMérieux) was ordered. We recently implemented the ME Panel in our multicenter health system. We assessed ME Panel use for the 6-month period following test implementation.

Methods

A testing algorithm was developed, vetted with our system-wide Infectious Diseases (ID) and Neuro-ID Services, and used as the basis for the education of the Emergency Medicine, Internal Medicine, Hospitalist, Pediatric, and Critical Care Medicine Services. Algorithm elements were embedded in the electronic medical record (EMR). Lab records and EMRs were reviewed for all patients tested by ME Panel or cerebrospinal (CSF) culture. Lab results, baseline demographic and underlying medical history, and results of singleplex viral PCR CSF tests and the multiplex NY State Encephalitis PCR Panel (NYS Panel, Wadsworth Laboratory, Albany, NY) were recorded. ME Panel results were compared with other findings.

Results

115 ME Panels were performed, with 5 (4%) positives [1 N.meningitidis, 1 H.influenzae, 1 cytomegalovirus (CMV), 1 Herpes simplex virus type 1 (HSV1), and 1 varicella zoster virus (VZV)]. Other findings were consistent with true infection for the N. meningitis, HSV and VZV; the CMV was likely reactivation. Significance of the H. influenzae was unclear. There were 830 CSF cultures, with 38 (4%) positive; 5 of the 38 were ME Panel targets. 29 NYS Panels were sent [1 positive each for Human Herpesvirus 6 (HHV6) and Epstein Barr Virus (EBV)]. Finally, 7 singleplex PCRs were positive [5 HSV, 1 CMV and 1 HHV6], including one negative by ME Panel.

Conclusion

We did not find ME Panel overuse; rather, we found several cases for which the ME Panel could have given a more rapid diagnosis. We did identify areas for improvement in test ordering, such as minimizing duplicate testing (e.g., singleplex PCR) A multi-disciplinary approach engaging stakeholders in the lab, ID and Neuro-ID can assist appropriate test utilization and diagnostic stewardship.

Disclosures

All authors: No reported disclosures.
2174. Comparison of the Verigene® and the ePlex® Blood Culture Identification Panels for Gram-Positive and Gram-Negative Bloodstream Infections
Authors: Johnson J Kristie , Kpadeh-Rogers Zegbeh , Paszkiewicz Gwen , Claeys Kimberly C
Published: October 2019

Background

Rapid diagnostic testing for the management of bloodstream infections has become paramount to improving patient outcomes. The primary objective of this study was to assess the differences between 2 FDA approved instruments.

Methods

Retrospective study from August 2018 to April 2019 at the University of Maryland Medical Center. One positive blood culture from each patient was tested using the Verigene® blood culture Gram-positive (BC-GP) or Gram-negative (BC-GN) panels based on the Gram stain and then analyzed using the ePlex® Blood Culture Identification (BCID) Gram-positive (BCID-GP) or Gram-negative (BCID-GN) research-use-only panels and compared with culture results.

Results

The study consisted of 140 positive blood culture bottles. 14 bottles were excluded for a total of 55 GN and 71 GP bottles. Of the 55 GN bottles, 3 had 2 GN rods for a total of 58 GNRs. BCID-GN missed 1 P. aeruginosa, 2 S. maltophilia, and 1 E. coli for a 93% (53/57) positive agreement. The BCID-GN does not detect A. junii and therefore it was excluded. BC-GN did not identify 1 K. pneumoniae with a 98% (47/48) positive agreement. BC-GN does not include the detection of S. maltophilia (4), Serratia (4), Morganella (1), and B. fragilis (1)and these were excluded in the BC-GN analysis. CTX-M was the only resistant marker detected and both panels identified it correctly. 5 samples using the BCID-GN also detected Pan Gram-Positive; 3 grew GP organisms, the other 2 only grew E. coli. Of the 71 GP bottles, 3 had two GP bacteria totaling 74 GPs. BCID-GP missed 1 S. aureus, 1 invalid, and called an E. faecalis that was not identified by the reference method for a 99% (72/73) positive agreement. BC-GP does not detect Micrococcus (6) or E. gallinarum (1) and missed 1 S. mitis/oralis for a 99% (66/67) positive agreement. 18 samples were positive for mecA detected by both panels. 4 samples were vanA/B positive; 1 by BCID-GP was sensitive to vancomycin and not detected by BC-GP. BCID-GP detected 1 sample as Pan Gram-negative although a GNR was not detected.

Conclusion

BothVerigene® and ePlex® GP and GN panels have a high percent positive agreement. Laboratories should take into consideration the epidemiology of their bloodstream infections when deciding on panels for the rapid detection of bloodstream infections.

Disclosures

All authors: No reported disclosures.
2176. A New Rapid Test for Detection of The Cefazolin Inoculum Effect (CIE) in Methicillin-Susceptible Staphylococcus aureus (MSSA)
Authors: Carvajal Lina P , Ordonez Diaz Karen M , Cristancho Quintero Edilberto , Echeverri Aura M , Vargas Sandra , Porras Jessica , Rincon Sandra , Seas Carlos , Luna Carlos , Arias Cesar A , Reyes Jinnethe
Published: October 2019

Background

Most MSSA harbor one of the four different variants of β-lactamase (BlaZ) (A, B, C and D). The CIE is defined as an MIC >16 μg/mL when a high inoculum (107 CFU/mL) is used and depends on the presence of BlaZ. The presence of the CIE has been associated with therapeutic failure in invasive MSSA infections. In some countries of South America, the prevalence of CIE is high, ranging from 36% to 51% (Colombia and Argentina, respectively). Type A BlaZ is most often associated with the CIE due to its high affinity for cefazolin. Here, we developed a rapid test based on the premise that the extracellular form of BlaZ is responsible for the CIE. We aimed to identify invasive MSSA that exhibit the CIE and validate the test in two cohorts of isolates from patients in Colombia and Argentina

Methods

152 MSSA clinical isolates were collected from Colombia (n = 71) and Argentina (n = 81). We determined MIC at standard and high inoculum. We developed a test using induction of BlaZ with ampicillin (150 μg/mL) for 20 minutes and, using the supernatant for incubation with nitrocefin for 30 min. A change in color from yellow to red was considered positive. MSSA TX0117 (BlaZ +, with the CIE), ATCC 29213 (BlaZ-negative) and ATCC 25923 (BlaZ + lacking the CIE) were used as controls. BlaZ typing of all Argentinian isolates was available by sequencing

Results

A high proportion (43%) of MSSA exhibited the CIE (34% and 52% of Colombian and Argentinian isolates, respectively) by MIC. The rapid test identified 76% of isolates exhibiting the CIE and correctly ruled out all isolates lacking the CIE (sensitivity 80%, specificity 100%). Furthermore, the rapid test detected all isolates with the CIE that harbored Type A BlaZ from Argentina. Conversely, the test failed to identify the CIE in Argentinian isolates that produce type B and C BlaZ. The sensitivity and specificity of the rapid test for the Colombian isolates whose BlaZ type was unknown were 89% and 100%, respectively.

Conclusion

A rapid test of less than 2 h can readily identify MSSA isolates exhibiting the CIE. For isolates carrying type A BlaZ, which is highly associated with the CIE, the test had a sensitivity and specificity of 100%. Rapid identification of MSSA with the CIE may have important therapeutic consequences in deep-seated infections

Disclosures

All authors: No reported disclosures.
2186. Differentiation of Severe Fever with Thrombocytopenia Syndrome from Scrub Typhus
Authors: Sul Hyoung , Ra Yun Na , Kim Dong-Min , Kim Jieun , Hur Jian , In Jung Sook , Ryu Seong-yeol , Yeon Lee Ji , Huh Kyungmin , Gyung Kwak Yee , Keun Kim Young , Won Jeong Hye , Yeon Heo Jung , Sik Jung Dong , Bae In-Gyu , Lee Su-Jin , Hee Lee Sun , Hee Park Sun , Yeom Joon-Sup , Lee Hyungdon
Published: October 2019

Background

SFTS and scrub typhus have similar clinical features and difficult to differentiate. Thus, a study to develop a scoring system to differentiate between two diseases in a clinical setting before the confirmation of laboratory results was reported by Kim et al. However, the statistical power could be low because of low numbers of cases (21 SFTS, 91 scrub typhus), our study analyzed by increasing the number of cases to overcome these limitations.

Methods

We retrospectively collected data from 183 SFTS and 178 scrub typhus patients who visited the 21 hospitals in South Korea between October, 2013 and November, 2017. The study protocol was approved by the IRB of each institution. SFTS was diagnosed through detection of SFTS viral RNA using RT–PCR. Scrub typhus was diagnosed either detection of 56-kDa antigen of O. tsutsugamushi using nested PCR or ≥ 4 fold rise in IgM or IgG titer using indirect IFA. Statistical analyses were performed by using SPSS and Medcalc.

Results

To differentiate SFTS from scrub typhus, we applied the scoring system proposed by Kim et al. After multivariable logistic regression, altered mental status, leukopenia, prolonged aPTT, and normal CRP(≤ 1.0 mg/dL) were significantly associated with SFTS compared with scrub typhus. Each variable was scored by 1 point, with a total score of 0–4 points, the optimal cutoff value was > 1 for the ROC curve. A score > 1 had 92% sensitivity, 96% specificity for diagnosis of SFTS, with a ROC AUC of 0.974. Because the sensitivity was less than 95%, we changed the normal CRP criteria to ≤ 3.0 mg/dL. The modified scoring system had 97% sensitivity, 96% specificity for diagnosis of SFTS, with an AUC of 0.983, and it showed a statistically higher accuracy than original scoring system (P = 0.0487). In this study, four factors for predicting SFTS were newly developed: leukopenia, prolonged aPTT, normal CRP (≤3.0 mg/dL), and elevated CK (>1,000 IU/L). Our study scoring system had 97% sensitivity, 98% specificity for diagnosis of SFTS, with an AUC of 0.992, and it showed a statistically higher accuracy than original scoring system (P = 0.0308).

Conclusion

In conclusion, we can easily differentiate SFTS from scrub typhus by using our scoring system of leukopenia, prolonged aPTT, normal CRP, and elevated CK in the endemic area.

Disclosures

All authors: No reported disclosures.
112. Physiological Signature of Bloodstream Infection in Critically Ill Patients
Authors: Zimmet Alex , Clark Matthew , Gadrey Shrirang M , Bell Taison , Randall Moorman J , Moore Christopher
Published: October 2019

Background

Bloodstream infection (BSI) is associated with high mortality rates in critically ill patients but is difficult to identify clinically. This uncertainty results in frequent blood culture testing, which exposes patients to additional costs and the potential harms of unnecessary antibiotics. Accordingly, we aimed to identify signatures in physiological data from critically ill adults that characterize BSI.

Methods

We reviewed all blood culture, vital sign, laboratory, and cardiorespiratory monitoring (CRM) data from patients admitted to the medical and surgical/trauma ICUs at the University of Virginia Medical Center from February 2011 to June 2015. Blood culture results were categorized as positive, negative, or contaminant. For the BSI population, we included data obtained within 12 hours before or 24 hours after the acquisition of a positive blood culture. The control population included data greater than 12 hours before or 24 hours after the acquisition of a positive blood culture, and all data from patients without BSI. We used multivariable logistic regression to identify the physiological characteristics of BSI.

Results

We analyzed 9,955 ICU admissions with 144 patient-years of vital sign and CRM data (1.3M hourly measurements). The average age was 59 years; the population was mostly Caucasian (81%) and male (56%). There were 5,671 (57%) admissions with ≥1 blood culture, and 744 (7%) had a BSI. The in-hospital mortality rate for patients with BSI was 28% vs. 12% for all others. The physiological signature of BSI was characterized by abnormalities in 12 parameters (Figure 1)—e.g., BSI was more likely in patients with a higher pulse and lower platelets. Several associations were nonlinear—e.g., temperature and WBC had U-shaped relationships with BSI. The internally validated C-statistic was 0.77.

Conclusion

Statistical modeling revealed a clinically sensible physiological signature of BSI that could assist with bedside decisions regarding the utility of blood culture testing in critically ill adults.

Disclosures

All authors: No reported disclosures.
2193. Factors Impacting the Duration of Antimicrobial Therapy for Community-Acquired Pneumonia
Authors: Sandhu Avnish , Goldman Erin , Polistico Jordan , Polistico Sarah , Oudeif Ahmed , Aranha Anil , Murray Kyle P , Zhao Jing , Mynatt Ryan , Pogue Jason M , Dhar Sorabh
Published: October 2019

Background

Pneumonia is a common cause of infection associated with hospitalization. Treatment durations for community-acquired pneumonia (CAP) often exceed guideline recommended durations of 5–7 days without a clear explanation. The objective of this study was to determine factors that may lead to durations exceeding this recommendation.

Methods

A retrospective chart review of 89 patients admitted to the Detroit Medical Center (DMC) for the treatment of pneumonia was conducted. Demographics, clinical signs and symptoms, antibiotic data, pneumonia severity score (CURB 65), risk factors for resistance, microbiology results, and outcomes were recorded and analyzed for factors associated with increased durations of antibiotics. Average durations of antibiotics and durations of antibiotics greater that 7 days were assessed for each risk factor.

Results

Average durations of antibiotics was 9 days (SD 3.8) for the cohort, and 55 (61%) received durations of > 7 days. Average durations of antibiotics for risk factors are shown in Table 1. Factors associated with durations of antibiotics longer than 7 days are shown in Table 2. There was a trend toward longer average durations of antibiotics for persons with risk factors for resistance [Drug Resistance in Pneumonia (DRIP) score ≥ 4 (increased duration of antibiotics by 1.7 days, P = 0.07] and those with a positive legionella antigen [increased durations of antibiotics by 6.6 days, P = 0.07].

Conclusion

Specific risk factors could not be associated with increased durations of antibiotics, although there was a trend toward longer durations for persons with markers for resistance and positive legionella testing. Efforts to reduce durations of antibiotics must target global clinician antibiotic prescribing patterns and not specific risk factors.

Disclosures

All authors: No reported disclosures.
2198. Weak Interobserver Reliability in the Clinical Diagnosis of Pneumonia Among Infectious Disease Trained Physicians
Authors: Sheffield Virginia , Dickson Robert , Chanderraj Rishi
Published: October 2019

Background

Pneumonia remains a common global cause of death. Varied definitions of pneumonia rely on clinical features, imaging, and microbiological data. The Center for Diseases Control/National Healthcare Surveillance Network (CDC/NHSN) definition is used to study population-level trends. Prior studies have revealed discordance in components of the definition, yet reliability of overall clinical diagnosis has not been evaluated, nor has it been compared with the surveillance definitions. This study was designed to determine the overall concordance in the diagnosis of pneumonia by Infectious Diseases (ID) clinicians and the agreement between this and the surveillance definition. We then set out to determine which clinical features were weighted most heavily in provider decision-making.

Methods

Using an iterative approach with input from ID and Pulmonary Medicine physicians, we designed and refined an adjudication tool for diagnosis of pneumonia that consolidates clinical features, laboratory data, and imaging. Cases were analyzed by strict CDC/NHSN surveillance criteria and adjudicated independently by ID-trained physicians based on overall clinical opinion. Kappa coefficient (κ) was used to determine diagnostic reliability, and a random forest model was used to identify clinical factors most heavily weighted by physicians.

Results

Twenty-eight cases were adjudicated by three ID-trained physicians. Overall, interrater agreement was low (κ = 0.438). In comparing providers’ clinical adjudication with CDC/NHSN criteria, agreement was even worse (κ range 0.125 to 0.378). Among specific clinical features, positive culture growth strongly informed clinician diagnosis of pneumonia, while chest imaging did not play a significant role.

Conclusion

Overall agreement in the clinical diagnosis of pneumonia is poor, even among ID-trained physicians. Culture results more strongly inform clinician decision-making than does chest imaging. The surveillance definition used by the CDC/NHSN has only weak agreement with in-practice clinical assessment. These results underscore the need for more precise diagnostic tools in cases of suspected pneumonia.

Disclosures

All authors: No reported disclosures.
113. Understanding the Changes in Infective Endocarditis Admission in Pennsylvania During the Opioid Crisis
Authors: Meisner Jessica A , Anesi Judith A , Anesi Judith A , Chen Xinwei , Grande Dave
Published: October 2019

Background

Nationwide, there has been a rise in cases of infective endocarditis (IE) correlating with the rise of the opioid crisis. Pennsylvania (PA) has the third highest rate of drug overdose deaths in the country, with Allegheny and Philadelphia counties having the highest rates in the country. With this study, we evaluated how IE has changed in the face of the opioid crisis with respect to the population impacted and associated healthcare utilization in PA.

Methods

We performed a retrospective cohort study of all adults admitted to an acute care hospital in PA between January 2013 and March 2017 with a diagnosis of IE. Patients were identified through the Pennsylvania Health Care Cost Containment Council (PHC4) via billing codes. Exposed patients were those with drug use-associated IE (DU-IE); the unexposed group was those with non-DU-IE. We determined the number of admissions and geographical distribution of IE and DU-IE in the state. We then assessed for differences in hepatitis C (HCV) and HIV serostatus, length of stay (LOS), insurance status, total hospital charges, and rates of valve surgery between the two groups.

Results

There were 17,224 admissions for IE in PA during the study period, of which 11.2% were DU-IE. In Allegheny and Philadelphia counties, 14.4% and 20.5% were from DU-IE, respectively. DU-IE cases increased from 6% in 2013 to 17% in 2017, P < 0.001. We found several significant differences between the DU-IE and non-DU-IE groups: DU-IE group was younger (median 33 vs. 69 years old, P < 0.001); the LOS was longer in the DU-IE group (10 vs. 7 days, P < 0.001); the percentage of patients leaving Against Medical Advice was higher in DU-IE group (15.7% vs. to 1.1%, P < 0.001); a higher proportion of the DU-IE group were HCV and HIV seropositive (27.1% vs. 3.3% for HCV, 2.4% vs. 0.74% for HIV, P < 0.001). See figures for complete results.

Conclusion

Pennsylvania had an increase in the number of IE cases over the last 4 years, driven by the opioid crisis, with Philadelphia and Alleghany counties being the most impacted areas. While this study is limited by the use of claims data, it demonstrates the downstream effects of the opioid crisis on the patient population at risk and the healthcare system due to longer and costlier hospital stays. This study supports the need for innovative and integrative care models to support them.

Disclosures

All authors: No reported disclosures.
2211. Impact of Early Fiberoptic Bronchoscopy on Microbiological Diagnostic Rate and Clinical Outcomes of Pneumonia in Acute Leukemia Patients
Authors: Sakurai Aki , Bala-Hampton Justin E , Mulanovich Victor E , Wierda William G , Cortes Jorge E , Adachi Javier
Published: October 2019

Background

Fiberoptic bronchoscopy with BAL (FOB) remains the cornerstone in the diagnosis of pneumonia in immunocompromised patients; however, there is no uniform agreement on the best timing for FOB, and its impact on microbiological diagnostic rate and clinical outcome has not been established.

Methods

Retrospective study (October 2017–December 2017, July 2018–January 2019) at MD Anderson Cancer Center. The medical records of adult patients with AML, MDS or ALL who developed pneumonia (CAP, HCAP, HAP excluding VAP) and underwent FOB were reviewed. By definition, patients who underwent FOB within 48 hours after the diagnosis of pneumonia were categorized as early FOB group. We compared demographic, clinical, microbiological data, and outcomes between two groups. Data were analyzed via χ 2, Fisher’s exact and Wilcoxon rank-sum test and logistic regression.

Results

Of 140 patients included, 33 patients (24%) had early FOB and 107 patients (76%) had late FOB. There was no significant difference between two groups in demographic features, radiological findings, ANC and pneumonia severity index. Microbiological diagnostic rate of FOB did not differ between early FOB and late FOB: identification of pathogenic microorganisms (33.3% vs. 36.5%, p = 0.837), bacteria (6.1% vs. 13.1%, P = 0.36), fungi (18.2% vs. 12.2%, P = 0.39) and respiratory virus (12.1% vs. 16.8%, P = 0.6), respectively (Figures 1 and 2). On univariate analysis, the duration of intravenous antibacterial therapy was shorter in early FOB, with a median duration of 8.5 days (IQR 6.5–12) in early FOB and 11 days (IQR 8–18) in late FOB (P = 0.0047) (Figure 3). Multivariable logistic regression analysis showed that late FOB (OR 3.26, 95% CI 1.41 to 7.53, P = 0.0057) and negative bacterial culture on FOB (OR 3.06, 95% CI 1.01 to 9.22, P = 0.048) were significantly associated with longer duration of intravenous antibacterial therapy (≥10 days). There was no significant difference in ICU admission, 30-day and 60-day mortality and re-admission rate.

Conclusion

Early FOB was associated with shorter duration of intravenous antibacterial therapy for pneumonia in acute leukemia patients, which has an important impact on both optimization of antimicrobial therapy for patients and improvement of antimicrobial stewardship.

Disclosures

All authors: No reported disclosures.
2218. Feasibility of Automated Prediction of Drug Resistance in Pneumonia in the Veteran Population.
Authors: Christensen Matthew A , Jones Barbara E , Babbel Danielle , Sutton Jesse D , Spivak Emily S , Haroldsen Candace , Stevens Vanessa W , Jones Makoto M , Samore Matthew H
Published: October 2019

Background

To enhance antimicrobial decision-making in community-onset pneumonia, several manually calculable clinical scores have been proposed to predict drug-resistant organisms (DRPs), most commonly methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The Drug Resistance in Pneumonia (DRIP) score includes 10 features that can be calculated by providers at the bedside but is potentially automatically extractable from an electronic health record (EHR). We aimed to explore the feasibility of calculating an automated “eDRIP” score from the EHR in the Veteran’s Affairs (VA) population.

Methods

We extracted patient characteristics, features relevant to the DRIP score, and detection of DRPs among all inpatient admissions for pneumonia between August 29, 2010 and July 31, 2013 at VA hospitals nationwide using EHR data from the VA corporate data warehouse. We calculated an eDRIP score for each admission. We compared the prevalence of each electronically extracted feature to that reported in a separate study of manually extracted factors performed at the Salt Lake City VA by Babbel et al, and to the original DRIP score validation cohort from Webb et al.

Results

Among 101,462 pneumonia admissions across 114 VA hospitals, 4% had a DRP detected on culture, 25% had an eDRIP ≥ 4, and 50% received broad-spectrum antibiotics. The Salt Lake City VA demonstrated slightly lower prevalence of eDRIP factors than the national population (table). Within the Salt Lake City VA, the EHR cohort and manually extracted Babbel cohort demonstrated similar prevalence of detected DRP’s, DRIP ≥ 4, and 8 of 10 features involved in the DRIP score (table). The eDRIP identified fewer hospitalizations with poor functional status and residence in long-term facilities.

Conclusion

In a large population of veterans admitted for community-onset pneumonia, automated extraction of an eDRIP score from the EHR was promising, though in need of revision. While some extracted features had similar prevalence to manual review, others differed by a factor of 10 or more, which may reflect issues with data extraction. Further work is needed to optimize feature extraction and compare electronic to manual DRIP scores to determine its utility within the VA population.

Disclosures

All authors: No reported disclosures.
2220. Comparative Incidence and Burden of Respiratory Viruses Associated with Hospitalization in Adults
Authors: Sieling William , Oberhardt Matthew , Zachariah Philip , Vargas Celibell , Barrett Angela , Phillips Matthew R , Finelli Lyn , Saiman Lisa
Published: October 2019

Background

The population-based incidence and burden of community-onset non-influenza respiratory viruses associated with hospitalization in adults has not been systematically assessed.

Methods

On admission, patients with respiratory symptoms are tested for respiratory viruses by multiplex polymerase chain reaction (BioFire FilmArray Respiratory Panel) as per standard of care at our university teaching hospital (1160 beds). A retrospective study was performed to identify adults who had influenza, parainfluenza virus (PIV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), or adenovirus (AV) detected within 3 days of admission from October 2017 to October 2018. To calculate population-based incidence per 100,000 persons (using 2010 US Census data), the number of cases was adjusted by the hospital’s percent market share for zip codes as determined by New York State’s all payer data reporting system. To improve the incidence estimate’s reliability, only cases living in zip codes for which the hospital had ≥ 60% market share were included. We compared median length of stay (LOS), ICU admission, and in-hospital mortality associated with each virus.

Results

Influenza A (H3) had the highest overall incidence followed by Influenza B and RSV. For each virus, the highest incidence was observed in adults ≥ 65 years old (figure). Overall, 12.9% of cases were hospitalized in the ICU and 4.7% died during hospitalization (table). AV, hMPV, and RSV were associated with the longest LOS. AV, PIV, and RSV were associated with the largest proportion of ICU admissions and deaths.

Conclusion

While Influenza A (H3) and Influenza B were associated with the highest population-based incidence, non-influenza respiratory viruses caused substantial morbidity in older adults. Compared with influenza viruses, AV, PIV, and RSV were associated with greater severity determined by ICU admissions and death.

Disclosures

All authors: No reported disclosures.
2222. Impact of Empiric Aminoglycoside Usage on Outcomes in Bacterial Pneumonia
Authors: Albin Owen , Patel Twisha S , Henig Oryan , Valley Thomas , Pogue Jason M , Petty Lindsay A , Mills John , Brancaccio Adamo , Kaye Keith S
Published: October 2019

Background

Although aminoglycosides are recommended as part of empiric combination therapy in selected patients with healthcare-associated pneumonia, their efficacy and safety remains unclear. The objectives of this study were to evaluate the impact of empiric aminoglycoside treatment on microbiologic cure, recurrent pneumonia and death, and acute kidney injury (AKI) among hospitalized patients treated for pneumonia who were clinically cured.

Methods

This was a nested cohort study including 441 hospitalized subjects with confirmed bacterial pneumonia who achieved clinical cure. All subjects had positive respiratory cultures at the beginning of therapy and also had cultures obtained at the time of antibiotic completion. Subjects with the same pathogen present at both the beginning of and at the end of treatment were categorized as microbiologic failure and all others were categorized as microbiologic cure. Serum creatinine was measured at both the beginning and end of therapy, with an absolute increase in serum creatinine of 0.5 mg/L or greater defined as AKI. Composite outcomes of 30- and 90-day recurrent pneumonia or death following the clinical cure of the index pneumonia were captured. Patients who received empiric aminoglycoside therapy were compared with patients who did not receive aminoglycoside therapy.

Results

Of 441 included subjects, 14.5% (N = 64) received aminoglycoside therapy and 85.5% (N = 377) did not. The mean age was 54.7 years, with 70.5% male and 78.2% white. Characteristics of the two groups (including Charlson Comorbidity Indices and APACHE II scores) were similar. Rates of microbiologic cure, death/recurrent pneumonia at 30- and 90-days and AKI and were similar in both groups (table). In subgroup analyses restricted to different pathogen groups these associations remained unchanged.

Conclusion

Among hospitalized patients with pneumonia who were clinically cured, empiric aminoglycoside therapy was not associated with an increased likelihood of microbiologic cure, death or recurrent pneumonia or AKI.

Disclosures

All authors: No reported disclosures.
2226. Impact of Prior and Concomitant Antibacterial Therapy on Outcomes in the ASPECT-NP Randomized, Controlled Trial of Ceftolozane/Tazobactam (C/T) vs. Meropenem (MEM) in Patients with Ventilated Nosocomial Pneumonia (NP)
Authors: Wunderink Richard G , Bruno Christopher , Martin-Loeches Ignacio , Kollef Marin , Timsit Jean-Francois , Yu Brian , Huntington Jennifer A , Li Linping , Jensen Erin , Wolf Dominik , Butterton Joan R , Rhee Elizabeth G
Published: October 2019

Background

NP is a frequent healthcare-acquired infection associated with high mortality; rising resistance rates among causative Gram-negative pathogens require new treatment options. In the randomized, controlled, double-blind, phase 3 ASPECT-NP trial, C/T (at double the initially approved dose) was noninferior to MEM for ventilated NP in both primary and key secondary endpoints. Here we evaluate the impact of prior and concomitant Gram-negative antibacterial therapy on outcomes in that trial.

Methods

Mechanically ventilated patients with ventilator-associated or hospital-acquired pneumonia were randomized 1:1 to 3 g C/T or 1 g MEM, both by 1-h IV infusion every 8 hours for 8–14 days. Patients could receive ≤24 hours of active antibacterial therapy within ≤72 hours prior to first dose; longer durations were permitted in case of prior treatment failure (i.e., signs and/or symptoms of the current episode of ventilated NP persisted/worsened despite ≥48 hours of treatment). At sites with MEM-resistant Pseudomonas aeruginosa rates ≥15%, patients could optionally receive up to 72 h of adjunctive empiric aminoglycoside (amikacin was recommended) until study drug susceptibility was confirmed. Primary and key secondary endpoints, respectively, were 28-d all-cause mortality and clinical response at test of cure (TOC; 7–14 days after the end of therapy) in the intent to treat (ITT) population (all randomized patients).

Results

In the C/T arm, 285/362 (79%) ITT patients received prior systemic Gram-negative therapy and 103/362 (28%) received adjunctive aminoglycoside, compared with 288/364 (79%) and 112/364 (31%) patients, respectively, in the MEM arm. In the microbiologic ITT population, causative pathogens in patients failing prior therapy at the time of enrollment (C/T 15%, MEM 11%) were mainly Klebsiella spp (33%), P. aeruginosa (17%), Escherichia coli (14%), and Acinetobacter baumannii (8%). Mortality and cure rates were comparable between C/T and MEM regardless of receipt of prior systemic or adjunctive Gram-negative therapy (table).

Conclusion

Prior and adjunctive Gram-negative antibacterial therapy did not affect the relative efficacy of C/T (at the 3-g dose) vs. MEM in these high-risk patients with Gram-negative ventilated NP.

Disclosures

All authors: No reported disclosures.
2232. A Global Phase 3 Study of Delafloxacin (DLX) Compared with Moxifloxacin (MOX) in Patients with Community-acquired Bacterial Pneumonia (CABP)
Authors: Salata Robert , Alvarez-Sala Rodolfo , Horcajada Juan P , Lawrence Laura , Quintas Megan , Li Yang , Cammarata Sue
Published: October 2019

Background

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

Methods

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

Results

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

Conclusion

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

Disclosures

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

Background

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

Methods

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

Results

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

Conclusion

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

Disclosures

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

Background

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

Methods

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

Results

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

Conclusion

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

Disclosures

All authors: No reported disclosures.