bluuebunny/crossref_metadata_2025 huggingface dataset:
1766. Osimertinib-Associated Progressive Multifocal Leucoencephalopathy
Authors: Gilotra Tarvinder S , Eranki Ambika P
Published: October 2019

Background

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of white matter in the central nervous system (CNS) caused by reactivation of John Cunningham (JC) virus. Drug-induced PML is increasingly reported with the widely used biological immunosuppressant drugs and molecular targeted antineoplastic agents. Monoclonal antibodies were the pioneer drugs to be associated with PML including the prototypical natalizumab.

Methods

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been rarely described in this context with few case reports of ibrutinib-associated PML. Osimertinib, a third-generation EGFR TKI, was recently FDA-approved for the first-line treatment of metastatic non-small-cell lung cancer (NSCLC), and to the best of our knowledge has never been associated with PML. We describe a case report of a rapidly progressive PML likely associated with osimertinib therapy.

Results

A 85-year-old female with history of NSCLC, on osimertinib, was admitted with progressively worsening left hemiparesis, facial palsy, unsteady gait, recurrent falls, and episodic confusion over a period of month. Brain magnetic resonance imaging revealed foci of non-enhancing increased T2 and fluid-attenuated inversion recovery (FLAIR) signal intensity in the periventricular and bilateral cerebral subcortical white matter. MRI cervical spine was unremarkable for acute enhancing lesions. Cerebrospinal fluid (CSF) was unremarkable for infectious etiology, oligoclonal bands, and cytology. The patient was readmitted 2 weeks later with worsening neurological deficits and new lesions in the bilateral middle cerebellar peduncles, pons, midbrain, and cerebral white matter. Positive CSF JC virus PCR lead to the final diagnosis of “probable” PML. Biopsy was deferred for high clinical suspicion of PML and procedural risks outweighing benefits. Osimertinib was likely contributing to PML in the absence of other immunosuppression.

Conclusion

Inhibition of tyrosine kinase-dependent pathways can potentially aid in the replication of JC virus per previously reported ibrutinib-associated PML. Clinicians should be aware of PML risk in patients on osimertinib and TKI therapy, especially those with positive serum JC virus serology.

Disclosures

All authors: No reported disclosures.
1791. Novel Metabolomics Approach for the Diagnosis of Respiratory Viruses Directly from Nasopharyngeal Specimens
Authors: Hogan Catherine , Le Anthony T , Mak Justin , Kumar. Sahoo Malaya , Cowan Tina , Pinksy Benjamin A
Published: October 2019

Background

Respiratory virus infections are important causes of morbidity and mortality among pediatric and adult patients. These viruses infect respiratory epithelial cells, where they may induce specific metabolite alterations. As a proof-of-concept, we investigate the novel use of liquid chromatography (LC) combined with quadrupole time-of-flight mass spectrometry (Q-TOF) for the study of host cell metabolite alterations to diagnose and differentiate respiratory viruses.

Methods

We studied nasopharyngeal swab samples positive for respiratory viruses by the eSensor Respiratory Viral Panel (GenMark Diagnostics, Carlsbad, CA). Banked, frozen samples (−80°C) stored in viral transport media were retrieved and thawed. Aliquots of 100 μL were centrifuged at 13.3 × g for 15 minutes, and the filtrate was analyzed by Agilent 6545 Quadrupole LC/Q-TOF (Agilent Technologies, Santa Clara, CA). Compounds were separated using a novel column arrangement based on hydrophobicity and charge using a quaternary solvent manager, followed by accurate mass analysis by LC/Q-TOF. Agilent Mass Profiler 3D principal component analysis was performed, and compound identification was completed using the METLIN metabolite database.

Results

A total of 235 specimens were tested by LC/Q-TOF, including 195 positive specimens [including adenovirus, coronavirus, influenza A H1N1 and H3N2, influenza B, human metapneumovirus, parainfluenza viruses 1, 2, 3, and 4, respiratory syncytial virus (RSV), and rhinovirus] as well as 40 negative clinical specimens. LC/Q-TOF primary component analysis (PCA) allowed preliminary identification of key metabolites that distinguished all virus-positive specimens compared with the negative group, and differentiated respiratory viruses from one another including between influenza A 2009 H1N1 and H3N2 subtypes (Figure 1).

Conclusion

Preliminary data from our LC/Q-TOF analysis show that respiratory viruses exhibit different host cell metabolomic profiles that allow viral differentiation to the species level, and for influenza A virus, the subtype level. This metabolomic approach has substantial potential for diagnostic applications in infectious diseases directly from patient samples, and may be eventually adapted for point-of-care testing.

Disclosures

All authors: No reported disclosures.
1982. A Diagnostic Stewardship Intervention for Clostridioides difficile: Impact of Stool Toxin Testing on Treatment of Adult Inpatients
Authors: Moss Jason , Forster Derek W , Arora Vaneet , Burgess David , Wallace Katie , Cotner Sarah , Burgess Donna R , Ribes Julie A , Suder Tigre , Myint Thein , VanHoose Jeremy , Jones C Randy
Published: October 2019

Background

Testing for Clostridioides difficile infection has been the subject of recent debate. Guidelines from the Infectious Diseases Society of America now support the addition of a stool toxin test to a positive nucleic acid amplification test (NAAT) as part of a multi-step testing algorithm. In November 2017, the University of Kentucky HealthCare system added stool toxin testing to any specimen positive for C. difficile by NAAT. This change was accompanied by face to face education with provider groups and clinical decision support in the form of interpretive verbiage added to the results that are reported into the electronic record. The objective of this study was to assess whether this diagnostic stewardship intervention made an impact on C. difficile treatment

Methods

We performed a retrospective review of adult patients admitted to UK HealthCare from November 1, 2017 through October 31, 2018 who tested positive by NAAT but negative by stool toxin test to determine whether or not they were treated. We also assessed treatment by service line to see whether there were treatment differences among these groups. A cost analysis was also performed.

Results

A total of 300 adult inpatients were positive for C. difficile by NAAT during the study period with 71% (213 patients) having a negative stool toxin test. Of those, 58% (123) were never started on C. difficile therapy and an additional 14% (30) had their therapy stopped after 48 hours. Only 28% (60) of these patients received a full course of therapy. Hospital medicine had the highest rate of non-treatment at 82%. Conversely, our solid-organ and bone marrow transplant services had the lowest rate of non-treatment at 31%. Overall, this approach was associated with an estimated 1470 oral vancomycin days avoided (5,880 doses) and a cost savings of $6,278.

Conclusion

The addition of stool toxin testing to NAAT combined with education and clinical decision support lead to a dramatic reduction of treatment for NAAT positive but toxin-negative patients. This form of diagnostic stewardship had a significant impact on therapy decisions and can be a powerful antimicrobial stewardship approach to decrease unnecessary treatment of C. difficile colonization.

Disclosures

All authors: No reported disclosures.
1984. A Multi-Disciplinary Team-based Quality Improvement Initiative to Reduce Clostridioides difficile Rates and Promote Antimicrobial Stewardship in Targeted Surgical Wards
Authors: Chang Amy , Smith Hurley , Sullivan Katrina , Meneses Joanne , Kirilcuk Natalie , Cooper-Sterling Jos , Kuo Jamie , Karam Amer , Schaffner Tammy , Mui Emily , Meng Lina , Deresinski Stan , Holubar Marisa
Published: October 2019

Background

At Stanford, two surgical wards, E3 and F3, were responsible for 1/5 of hospital-acquired Clostridioides difficile infection (HO CDI) cases in the fiscal year 2018 (FY2018). We used a quality improvement framework with a goal to reduce yearly HO CDI episodes by 1/2 on these wards.

Methods

A multidisciplinary quality improvement team was created with frontline nursing leaders and representatives from colorectal surgery, gynecology oncology, antimicrobial stewardship (ASP), infection prevention, and pharmacy. Coaching and instruction on quality improvement were provided as part of Stanford’s “Realizing Improvement through Team Empowerment” (RITE) program. Using A3 problem solving, root cause analysis identified key drivers, and interventions were performed. Cumulative HO CDI cases in FY2019 and weekly antibiotic days of therapy (DOT) on E3/F3 were monitored.

Results

Review of FY2018 HO CDI cases (n = 14) revealed the most common key driver as inappropriate antibiotic prescribing (8 cases, 57%). Multiple interventions were instituted (Figure 1). Three ASP interventions began February 2019: nursing questioned antibiotic choice/duration on daily interdisciplinary rounds (Figure 2), automatic infectious disease consultation for > 72 hours of piperacillin/tazobactam on gynecology/oncology patients, and twice-weekly rounds between ASP and a colorectal attending. Data from ASP/colorectal rounds from March 19, 2019 to April 16, 2019 showed means of 18.2 minutes taken for chart review and 4.4 minutes for discussion. 25 charts reviewed led to 16 (64%) ASP recommendations and 14/16 (87.5%) of recommendations accepted. Common interventions included: appropriate duration of antibiotics, clarification of the team’s planned duration, and review of microbiology data to narrow therapy. Mean DOT decreased from 35.28 to 21.61 (39%) since July 2018 (Figure 3). Patient volume and case mix index remained stable throughout, suggesting no impact on DOT. Though CDI cases did not decrease, interventions were in place for only 2 months (Figure 4).

Conclusion

While too early to determine its impact on HO CDI rates, a multi-disciplinary team approach utilizing A3 problem solving was successful in implementing effective ASP measures including nursing-led ASP and structured antibiotic timeouts.

Disclosures

All authors: No reported disclosures.
2003. Vancomycin Discontinuation Is Supported by-negative Nasal Methicillin-Resistant Staphylococcus aureus (MRSA) in Patients with Pneumonia
Authors: Pleasants Katherine A , Low Karly , Lucas Sara A , Kivlehan Audrey , Washburn Ronald G
Published: October 2019

Background

A negative nasal MRSA PCR test has a 98–99.6% sensitivity in confirming that MRSA is not the causative organism associated with pneumonia in hospitalized patients. Evidence supporting the clinical utility of nasal MRSA PCR testing in the Veteran patient population is limited, with no identified publications to date. The purpose of this project was to share outcomes associated with implementation of nasal MRSA PCR testing in the Veteran population to guide duration of vancomycin therapy.

Methods

This retrospective cohort quality initiative compared treatment of pneumonia that included vancomycin during a pre-Antimicrobial Stewardship Program (ASP) intervention phase (August 2013–February 2014) to an active ASP intervention phase (August 2017–March 2019). ASP intervention consisted of utilization of a negative nasal MRSA PCR as a rapid diagnostic test to support discontinuation of vancomycin prior to microbiologic culture results. Retrospective chart review evaluated vancomycin days of therapy (DOT), hospital length-of-stay (LOS), 30-day hospital readmission, and 30-day mortality. Patients admitted to the intensive care unit during the identified hospitalization were excluded.

Results

The average vancomycin DOT significantly declined by 1.08 days when comparing the pre-ASP intervention phase (N = 25) to the ASP-intervention phase (N = 47) (3.6 vs. 2.52 days, respectively; P = 0.0088). Mean hospital LOS decreased by 1.5 days (6.04 vs. 4.54 days, respectively, P = 0.0885). There was no significant difference in 30-day hospital readmission rate (12% vs. 8.5%) or 30-day mortality rate (12% vs. 10%).

Conclusion

Vancomycin DOT was reduced by 30% (1.08 days) and hospital LOS was reduced by 24.8% (1.5 days) in patients with pneumonia during a Vet. Affairs medical center’s utilization of negative nasal MRSA PCR testing to support vancomycin discontinuation. This project highlights the role of nasal MRSA PCR as a rapid diagnostic test to aid in diminishing empiric vancomycin usage and its associated toxicities.

Disclosures

All authors: No reported disclosures.
2004. Impact of Procalcitonin Roll-out Without Antimicrobial Stewardship Guidance in a Community Hospital Emergency Department
Authors: Mena Lora Alfredo J , Qasmieh Samah , Wenzler Eric , Borgetti Scott , Jhaveri Naman , Doyle Richard , Cortez Martin , Bleasdale Susan C
Published: October 2019

Background

Lower respiratory tract infections (LRTIs) are one of the most common infectious disease-related emergency department (ED) visits in the United States. The ID Society of America and the Agency for Healthcare Research and Quality support the use of procalcitonin (PCT) for antimicrobial stewardship (ASP) in LRTI. Though not widely available, awareness and access to PCT is rising. At our facility, PCT became available in February 2018. The aim of our study is to assess the impact of PCT at an urban community hospital and identify possible targets for ASP interventions.

Methods

Retrospective review of cases from February to August 2018. Cases from the ED were selected for review. Appropriateness of testing was assessed, defined as guideline-based use for cessation of antibiotics in uncomplicated LRTIs without critical illness or immunosuppression. Demographic variables and clinical characteristics, such as, diagnosis, antimicrobial use and PCT levels were obtained.

Results

PCT was ordered 268 times hospital-wide, of which 160 (60%) were in the ED. Ages ranged from 0–90, with an average of 47. Most cases were male (51%). Appropriate testing for LRTI occurred in 33 (29%) cases. Antimicrobials were used in 75% of cases with low (< 0.5) PCT levels (Figure 1). Length of stay (LOS) was higher in groups that received antimicrobials (Figure 2). Testing was not appropriate in 127 cases (71%), with upper respiratory (21%), soft-tissue (17%), genitourinary (15%) and abdominal (13%) infections as the most common reasons for testing. Other diagnosis included alcohol withdrawal, seizures and altered mental status. Cumulative cost of PCT testing was $24000, of which $19050 was not consistent with guidelines.

Conclusion

Clinicians routinely ordered PCT in the ED. Antimicrobials were used for LRTIs despite low PCT levels. This may have contributed to higher LOS and excess antimicrobial use. Unwarranted PCT testing had a cost of $19050. As PCT becomes widely available in hospitals across the United States, education and decision support by ASP to clinicians may be needed to enhance guideline-appropriate evidence-based use of PCT. Targeted ASP interventions in the ED may have cost savings by reducing excess testing, length of stay and improving antimicrobial use.

Disclosures

All authors: No reported disclosures.
2018. The Global Point Prevalence Survey of Antimicrobial Consumption and Resistance: Quantity and Quality of Antimicrobial Prescribing for Inpatients with Pneumonia in the Philippines in 2018
Authors: De los Reyes Mari Rose Aplasca , Hufano Maria Charmian M , Pauwels Ines , Versporten Ann , Goossens Herman
Published: October 2019

Background

Pneumonia is the most common indication for prescription of antibiotics in hospitals in the Philippines. We describe the quality and quantity of antibiotic prescribing for hospitalized pneumonia patients in the Philippines in 2018 (www.global-PPS.com).

Methods

A point prevalence survey was performed from September to December 2018 in 28 public and private hospitals in Luzon, Mindanao, and Visayas regions. Ward- and patient-level data were collected using a standardized methodology and entered through a web-based application. We analyzed all antibiotic (ATC J01) prescriptions for inpatients with pneumonia.

Results

Of all hospitalized patients, 16.2% (n = 1516) received one or more antibiotic (J01) for treatment of pneumonia, majority (78.3%) of which were for community-acquired pneumonia (CAP). In adults, the most commonly used antibiotics were azithromycin (19.5%), ceftriaxone (19.0%), and piperacillin/enzyme inhibitor (13.2%) for CAP and meropenem (19.8%), piperacillin/enzyme inhibitor (18.9%), and levofloxacin (8.6%) for healthcare-associated pneumonia (HAP). In neonates and children, cefuroxime was used most often (20.1%) for treatment of CAP, followed by ampicillin (16.7%) and amikacin (15.3%). Children and neonates with HAP were most commonly treated with amikacin (18.7%), meropenem (15.7%), and ampicillin (10.4%). Overall, 16.0% of all antibiotic prescriptions for pneumonia were based on microbiological results, 11.3% for CAP and 33.9% for HAP. Microbiology-based prescriptions were most commonly targeted at ESBL-producing Enterobacteriaceae (8.4%). Further analysis of quality indicators showed that up to 80.0% of all prescriptions for pneumonia were compliant to local guidelines and reason in notes was documented for 81.0% of prescriptions. However, the stop or review date of antibiotic treatment for pneumonia was less documented (27.8%).

Conclusion

Global-PPS data provided valuable insights into the quantity and quality of antibiotic prescribing for pneumonia inpatients. These results will be fedback to the Department of Health, medical societies, and hospitals for prioritization of targets and policies toward the improvement of the Philippine antimicrobial stewardship program.

Disclosures

All authors: No reported disclosures.
2050. Effect of a Stewardship Intervention on Post-Prescriptive Antibiotic Timeouts in Nursing Homes
Authors: Liao Chi-Yin , Ford James H , Nace David A , Crnich Christopher
Published: October 2019

Background

Antibiotic overuse and misuse is a common problem in nursing homes (NHs). Meaningful improvements in the quality of antibiotic prescribing in NHs may be improved through post-prescriptive interventions (antibiotic timeouts) focused on stopping, streamlining and/or shortening ongoing antibiotic treatments. A recently completed trial of a complex antibiotic stewardship intervention provided us with an opportunity to explore to what extent NH providers engaged in antibiotic timeouts at baseline and the effects of the intervention on these behaviors.

Methods

Data on antibiotic prescriptions in 11 NHs (6 intervention, 5 control) were collected for 12 months prior and 13 months after intervention introduction. We categorized antibiotic change events (ACEs) as: (1) changes in dose, frequency, or route for the same antibiotic, (2) change to another antibiotic with different spectrum, and (3) early discontinuation (stopped after 2 days or less). Modifications considered to be routine (e.g., Azithromycin dose reduction from 500 to 250 mg) were not considered a meaningful ACE. Frequency of ACEs both overall and by type were compared using a difference in difference (DID) approach.

Results

Of 2647 NH initiated antibiotic events, 376 (14.2%) were modified over the study period. The most common type of modification was a change in spectrum (n = 241, 64.1%) followed by early discontinuation of the antibiotic (n = 118, 31.4%). The difference in ACEs before and after the intervention as well as DID estimates are detailed in the Table.

Conclusion

The antibiotic stewardship intervention did not impact total ACEs but did appear to increase the frequency of discontinuation ACEs. An inability to capture data on shortening ACEs (e.g., reducing a treatment course from 14 to 7 days) was a limitation of this study. Additional research on how to foster more frequent and effective antibiotic timeouts in NHs is needed.

Disclosures

All authors: No reported disclosures.
2057. Outpatient Antibiotic Stewardship “Bundles up” in Winter with Peer Comparison, URI Order Set and Education: Is It Enough to Weather the Storm?
Authors: Akay Okan I , Dave Rohini , Khosla Amit , Kraska CherylAnn , Hopkins Brian J , Bork Jacqueline
Published: October 2019

Background

Inappropriate antibiotic use is a growing problem in the outpatient setting. Approximately 90% of all antibiotics are prescribed in outpatient practices. Nonetheless, 30–70% of antibiotic prescriptions (ARx) are unnecessary. Outpatient antimicrobial stewardship (AS) is much needed and the best approach is unknown. We used a bundle approach to outpatient AS during the winter months, by implementing a peer comparison (PC) report, upper respiratory infection (URI) order set and broad education.

Methods

This is a quasi-experimental project during the period October 2018 to March 2019 (FY19) to evaluate the impact of a bundled intervention in primary care clinics at the VA Maryland Health Care System. A historical control group from the same period the previous year (FY18) was used for comparison. The intervention included an AS directed didactic and URI order set followed by an email in 1/2019 with: (1) censored PC report (ARx/1,000 encounters) with outliers defined as above 1.5 × interquartile range, (2) URI order set reminder, and (3) education. The primary outcome was total ARx per 1,000 encounters in primary care clinics. A random sampling of 200 charts was done to compare proportion of antibiotic appropriateness and number of emergency department (ED) visits and adverse drug events (ADEs) in FY19 Q1 and FY19 Q2. Poisson regression was carried out, in addition to Χ2-statistic.

Results

There were 3,799 vs. 3,429 ARx in FY18 and FY19, respectively, with a rate difference of 3.3 ARx per 1,000 encounters (P = 0.0056). Q1 to Q2 ARx rate increased by 7.8 and 8.0 ARx per 1,000 encounters in FY18 and FY19, respectively. Forty-eight percent (28/58) of the providers confirmed receipt of email. There were 3 and 4 outliers in FY19 Q1 and Q2, respectively. Appropriate ARx for FY19 Q1 and Q2 was found to be 45% and 35% (P = 0.44), respectively. The most common indications were URI (18% vs. 18%), urinary tract infection (13% vs. 21%). ED visits (10% vs. 6%) were uncommon and there were no ADEs.

Conclusion

E-mail communication with bundled approach had no effect on ARx or antibiotic appropriateness; however general AS presence and URI order set tempered some use. Removing peer censoring, providing face-to-face education and intensifying antibiotic order sets are additional interventions to be implemented.

Disclosures

All authors: No reported disclosures.
2099. Use of Infectious Diseases Source-Specific Electronic Sepsis Order Sets is associated with Improved Survival in Sepsis: An Evaluation of 46 Hospitals in a Large Health Care System
Authors: Daragjati Florian , Sebastian Danielle , Roberts Phillip , Rashid Asifur , Erlinger Thomas , Fakih Mohamad G
Published: October 2019

Background

Compliance with evidence-based treatment bundles in patients with sepsis can lead to improved survival in persons with sepsis or septic shock. A way to ensure the adoption of best practices is the early use standardized order sets based on suspected source of infection.

Methods

The patient population was built by connecting electronic health record (EHR) to administrative data. In the EHR, we identified patients who had a sepsis discharge diagnosis code based on the International Statistical Classification of Disease and Related Health Problems (ICD−10), from August 1, 2018 to February 28, 2019. We evaluated the empiric use of sepsis order sets and patient outcomes. We adjusted for age, gender, Elixhauser Comorbidity Score (ECS), intensive care unit (ICU) status, and admission type. For the analysis, we included patients age 18 and older from facilities where we were able to match greater than 70 percent of patients. Matching was done by facility on medical record number and discharge date.

Results

There were 26,604 patients included in the analysis. The overall mortality rate was 10.67% (n = 2,839). Mortality associated with sepsis in patients that had a sepsis order set used was 8.92% (791/8,872), while for those whom a sepsis order set was not used was 11.55% (2,048/17,732). When mortality data were adjusted for age, gender, ECS, ICU status, admission type and hospital size, the use of sepsis order sets was associated with an adjusted odds ratio of 0.793 (95% CI 0.722, 0.868). In addition, in all sepsis patients who had an ICU admission, the use of the sepsis order sets was associated with an adjusted odds ratio of 0.804 (95% CI 0.725, 0.890). Similarly, in all sepsis patients who did not have an ICU admission, the use of the sepsis order sets was associated with an adjusted odds ratio of 0.688 (95% CI 0.556, 0.847).

Conclusion

The use of the standardized sepsis order sets in patients with sepsis was associated with a 20.7% relative risk reduction in mortality. In conjunction with rapid recognition of sepsis, early initiation of the sepsis order sets may lead to improved mortality in patients with sepsis.

Disclosures

All authors: No reported disclosures.
2134. Differential Changes in Breath Volatile Metabolites to Identify Carbapenem-Resistant Enterobacteriaceae (CRE) in a Murine Pneumonia Model
Authors: Ismail Nour , Albashash Hazem , Thalavitiya Acharige Mahesh J , Hejazi Mohamad , Leon Astudillo Carmen , Aloum Obadah , Koshy Seena , Fredenburgh Laura , Balasubramanian Raji , Skurnik David , Guillard Thomas , Koo Sophia
Published: October 2019

Background

CRE infections cause significant mortality, in large part because rapid identification of these infections is challenging. We tested the hypothesis that CRE and their isogenic carbapenem-susceptible counterparts have differential metabolic responses to carbapenem therapy.

Methods

We generated isogenic pairs of E. coli, E. cloacae, and K. pneumoniae by inserting a blaNDM-1-containing plasmid into carbapenem-susceptible E. coli, E. cloacae, and K. pneumoniae. We confirmed phenotypic meropenem (MPM) resistance per CLSI breakpoints for Enterobacteriaceae (MIC ≥4) in the NDM-1+ member and susceptibility (MIC≤1) in the NDM-1- member of each pair. We administered 2 × 108 CFU of each isolate intranasally to 23–28 g male C57BL/6J mice, infecting 6 mice with the NDM-1+ member and 6 with the NDM-1− member of each species pair (12 mice per bacterial species). 24 hours after infection, we treated 3 mice in each NDM-1+ and NDM-1− bacterial species cohort with MPM over 4 hours, and the other 3 mice in each cohort with saline over 4 hours as controls, confirming adequate infection (a target of 106 CFU/g of lung tissue) in quantitative lung homogenate cultures. We then collected breath samples from each mouse via tracheostomy using a murine ventilator, identifying all volatile metabolites in each sample using thermal desorption-gas chromatography/tandem mass spectrometry. We used Wilcoxon tests to examine differences in metabolite abundance between MPM and saline-treated control mice in the NDM-1+ and NDM-1− a member of each species pair, with a two-sided P-value threshold of < 0.1.

Results

Several breath volatile metabolites changed differentially within each NDM-1+/NDM-1- pair, outlined in Table 1 (E. coli), Table 2 (E. cloacae), and Table 3 (K. pneumoniae). Each listed metabolite that changed with MPM did not change with MPM in mice infected with each isogenic counterpart

Conclusion

There are differential in vivo metabolic responses with effective vs. ineffective treatment of mice with pneumonia caused by E. coli, E. cloacae, and K. pneumoniae pairs that are genetically identical other than blaNDM-1; this differential treatment response can potentially be used to identify these infections.

Disclosures

All authors: No reported disclosures.
2140. Utility of Respiratory Specimen Gram Stain for Predicting Final Culture Result in Patients with Clinically Diagnosed Pneumonia
Authors: Seadler Jessica , Smith Terri , Faust Andrew C
Published: October 2019

Background

Obtaining a high-quality respiratory tract specimen for Gram stain and culture in patients with suspected lower respiratory tract infections is recommended by the IDSA guidelines. However, conflicting results correlating Gram stain with final culture growth has led to questions about the utility of a respiratory specimen Gram stain. The purpose of this study was to assess the correlation of Gram stain with final culture in patients with pneumonia.

Methods

A retrospective chart review was conducted to evaluate adult inpatients with a diagnosis of pneumonia (based on the CDC surveillance definition) who had a respiratory specimen submitted for Gram stain and culture. A specimen was considered acceptable if less than ten epithelial cells were visualized under low power field. Each Gram stain was compared with the corresponding final culture. The primary outcome was to evaluate the correlation of Gram stain with final culture using positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity. A culture was considered negative if no bacteria were isolated or if only normal flora grew. Secondary outcomes were PPV and NPV based on antibiotic exposure prior to specimen collection, semi-quantitative number of bacteria on Gram stain, and collection method. Additionally, discordance between Gram stain and final culture morphology was evaluated.

Results

A total of 269 acceptable specimens were assessed. Of the 72 specimens with a positive Gram stain, 41 yielded bacteria in final culture (PPV: 56.9%). In contrast, 154 of the 197 specimens with a negative Gram stain were associated with negative final culture (NPV: 76.7%). The NPV of Gram stain was decreased when antibiotics were given for > 24 hours pre-specimen. The PPV of Gram stain improved as an increasing amount of bacteria were reported. Less invasive collection methods had a lower PPV but a higher NPV in comparison to invasive collection methods. Finally, the discordance rate between Gram stain and final culture morphology was low.

Conclusion

This study shows inconsistent results regarding the ability of Gram stain to predict final culture. Pneumonia should continue to be managed clinically and caution taken prior to adjusting empiric antimicrobial regimens based solely on the Gram stain.

Disclosures

All authors: No reported disclosures.
2142. Comparison of Molecular-Based vs. Conventional Culture-Based Screening Methods for Detection of Carriers of Extended-Spectrum β-Lactamases (ESBL) and Carbapenemases-Producing Enterobacteriacae (CPE)
Authors: Martischang Romain , Renzi Gesuele , François Patrice , Bonetti Eve-Julie , Cherkaoui Abdessalam , Pugin Jérôme , Schrenzel Jacques , Harbarth Stephan
Published: October 2019

Background

Active surveillance and contact precautions may prevent cross-transmission of ESBL-producing Enterobacteriaceae and CPE. Culture-based methods delaying results might increase risk of cross-transmission, and lead to unnecessary preemptive contact precautions. This observational cohort study compared rapid Loop-Mediated Isothermal Amplification (LAMP) assays to conventional culture-based methods for ESBL and CPE screening of critically ill patients.

Methods

This study was conducted in the adult ICUs at Geneva University Hospitals. We collected consecutive rectal ESwabs routinely performed, either for admission screening of high-risk patients or once weekly routine screening of all patients hospitalized in the ICU. Eazyplex® SuperBug CRE system (Amplex Biosystems) assays were performed directly on rectal Eswabs according to the manufacturer’s instructions. For the conventional culture-based method, we used chromID® ESBL agar (ESBL) coupled with chromID®OXA-48. Discordant specimens were retested using disk diffusion tests and the same LAMP assay on isolates. Microbiological turn-around times (TAT; from the reception in the laboratory to result notification) were collected.

Results

Overall, 290 rectal ESwabs were analyzed. ESBL and CPE prevalence were 16.7% and 1.0%, respectively. Three discordant isolates could not be further investigated and considered as LAMP false positive. Adjusted analytical performances were for CPE: 100% (95IC 100–100%) sensitivity, 99.6% (99.0–100%) specificity, 75% (32.6–100%) PPV, and 100% (100–100%) NPV, and for ESBL: 85% (73.9–96.1%) sensitivity, 98.8% (97.4–100%) specificity, 91.9% (83.1–100%) PPV, and 97.6% (95.7–99.5%) NPV. A decrease in TAT was observed when comparing LAMP screening assay against conventional method (50.3 hours vs. 6.2 hours; Figure 1). Figure 2 shows time reductions comparing both screening strategies.

Conclusion

Screening strategies based on LAMP could fasten discontinuation of unnecessary pre-emptive isolation time for patients at risk and earlier implementation of contact precautions for previously unknown carriers of ESBL or CPE.

Disclosures

All authors: No reported disclosures.
2154. Rapid Microorganism Identification From Blood and Enrichment Fluid Cultures Using MALDI-TOF Mass Spectrometry Following Abbreviated Incubation on Chocolate Agar Plates
Authors: Chew Rusheng , Otome Ohide , Harris Owen , Walton Aaron , Hewson Darrren , Luppino Michael , Cowan Raquel
Published: October 2019

Background

The more rapidly a pathogen can be identified in cases of sepsis, the more swiftly targeted therapy can be commenced. We aimed to evaluate the accuracy and clinical utility of a method for rapid microorganism identification from blood and sterile site fluid enrichment cultures using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in a high-throughput regional microbiology laboratory.

Methods

A drop of blood or fluid from cultures flagging positive was inoculated onto chocolate agar and incubated until MALDI-TOF MS analysis 5–6 hours later. Results obtained with conventional overnight incubation were used as controls. The number of isolates reliably and correctly identified, and recommendations for changes to clinical management were recorded. A pilot study was undertaken to demonstrate feasibility using a cut-off score of ≥2.0, following which the method was integrated into the laboratory workflow using a cut-off score of ≥1.7 (identification to genus level) because patient management can often be altered with this degree of accuracy.

Results

In the pilot study, 154/210 blood cultures (73.3%) were reliably identified (score ≥2.0) and, of these, 151 (98.1%) were correctly identified. The operational study included 144 blood cultures and 14 sterile site fluid enrichment cultures. 121 (76.6%) were reliably identified (score ≥1.7) and, of these, 117 (96.7%) were correctly identified. Four isolates (2.5%) were yeasts, 104 (65.8%) were Gram-positive bacteria and 50 (31.6%) were Gram-negative bacteria. 78 of the 104 bacteria (75.0%) were correctly identified. The median score for Gram-positives was 1.89 (IQR 0.36). For Gram-negatives, 47 of the 50 isolates (94.0%) were correctly identified. The median score for Gram-negatives was 2.29 (IQR 0.14). No yeasts were reliably identified. Recommendations for changes to clinical management were made for seven (3.8%) and nine patients (6.0%) in the pilot study and operational study, respectively. The method was easily integrated into the laboratory workflow and did not require additional staff.

Conclusion

We build on previous work by providing a simple method for rapid micro-organism identification which allows easy integration into a busy laboratory, and which improves clinical management.

Disclosures

All authors: No reported disclosures.
2158. Cost-Effectiveness and Budget Impact of a Point-of-Care Nucleic Acid Amplification Test for Diagnosis of Group A Streptococcal Pharyngitis in the United States
Authors: Karichu James , Cheng Mindy , Sickler Joanna , Munakata Julie , Bilir S Pinar , Kruger Eliza
Published: October 2019

Background

Group A streptococcal (GAS) pharyngitis is common in the United States (US). Each year, approximately 12 million people seek medical care for pharyngitis, accounting for ~2% of ambulatory care visits. The gold standard method for diagnosing GAS is culture. However, because culture is time intensive, rapid antigen detection tests (RADTs), with or without culture confirmation, are commonly used. Although RADTs provide results quickly, test sensitivity has been shown to be sub-optimal, which can lead to inappropriate treatment decisions. Recently, highly sensitive point-of-care nucleic acid amplification tests (POC NAAT), such as the cobas® Liat® System, have emerged. The objective of this study was to evaluate the cost-effectiveness (CE) and budget impact (BI) of adopting POC NAAT compared with RADT+culture confirmation to diagnose GAS pharyngitis from the US third-party payer perspective.

Methods

A decision-tree economic model was developed in Microsoft Excel to quantify costs and clinical outcomes associated with POC NAAT and RADT+culture over a one-year period. All model inputs were derived from published literature and public databases. Model outputs included costs and clinical effects measured as quality-adjusted life days (QALDs) lost. One-way and probabilistic sensitivity analyses were performed to assess the impact of uncertainty on results.

Results

CE analysis showed that POC NAAT would cost $44 per patient compared with $78 with RADT+ culture. POC NAAT was associated with fewer QALDs lost relative to RADT+ culture. Therefore, POC NAAT may be considered the “dominant” strategy (i.e., lower costs and higher effectiveness). Findings were robust in sensitivity analyses. BI analysis showed that adopting POC NAAT for diagnosis of GAS could yield cost-savings of 0.3% vs. current budget over 3 years. This is due to savings associated with testing, GAS-related complications, antibiotic treatment and treatment-associated complication costs.

Conclusion

Results suggest that adopting POC NAAT to diagnose GAS would be considered cost-effective and yield cost-savings for US payers relative to RADT+culture. Access to POC NAAT would be important to optimize appropriate GAS diagnosis and treatment decisions.

Disclosures

All authors: No reported disclosures.
110. Clinical Outcomes of Patients with Secondary Bacteremia in the Omadacycline Phase 3 Acute Bacterial Skin and Skin Structure Infections and Community-Acquired Bacterial Pneumonia Studies
Authors: Sakoulas George , Eckburg Paul B , Manley Amy , Tzanis Evan , Garrity-Ryan Lynne , Das Anita F , Curran Marla , Noble Bob , McGovern Paul C
Published: October 2019

Background

Low serum concentrations of tetracycline antibiotics may raise concerns on their efficacy in patients with secondary bacteremia, especially in comorbid patients and in those with higher acuity of illness. Omadacycline (OMC), an aminomethylcycline antibiotic, showed noninferiority to linezolid (LZD) in two acute bacterial skin and skin structure infections (ABSSSI) studies (Omadacycline in Acute Skin and skin structure Infections Study [OASIS]-1 and -2), or to moxifloxacin (MOX) in a community-acquired bacterial pneumonia (CABP) study (Omadacycline for Pneumonia Treatment In the Community study [OPTIC]). This analysis considers clinical outcomes in patients with secondary bacteremia identified in these studies.

Methods

Baseline blood cultures were taken from adult patients enrolled in Phase 3 randomized, double-blind clinical studies of OMC. Patients received ≥1 treatment dose: N = 1,347 ABSSSI (OMC n = 676; LZD n = 671); N = 774 CABP (OMC n = 386; MOX n = 388). Efficacy was evaluated by investigator assessment of clinical response at a post-treatment evaluation (PTE) 7–14 days (ABSSSI) or 5–10 days (CABP) after the last dose.

Results

Bacteremia was confirmed in 63 patients (3%) across the three studies. Staphylococcus aureus was the most common pathogen in patients with ABSSSI (N = 30: OMC n/N = 7/13; LZD n/N = 9/17), with a median treatment duration of median 9 days (OMC) and median 10 days (LZD). Streptococcus pneumoniae was the most common pathogen in patients with CABP (N = 33; OMC n/N = 11/15; MOX n/N = 11/18), with a median treatment duration of 11 days (OMC) and 14 days (MOX). Clinical success was numerically comparable between treatment groups within each study (figure) after completion of therapy.

Conclusion

The clinical successes of patients receiving OMC for ABSSSI or CABP with secondary bacteremia were comparable to results for LZD and MOX, respectively. Although limited by the small sample size, data from ABSSSI and CABP study patients with secondary bacteremia provide reassurance for the use of OMC. Real-world OMC data in patients with ABSSSI and CABP will be needed to assess outcomes in patients with additional comorbidities and/or higher acuity of illness.

Disclosures

All authors: No reported disclosures.
2216. Pneumonia in the ICU: Epidemiology and Outcomes
Authors: Blaha Michael , Zelus Casey , Cawcutt Kelly , Cawcutt Kelly , Marcelin Jasmine R , Marcelin Jasmine R , Kalil Andre C , Samson Kaeli
Published: October 2019

Background

The understanding of pneumonia epidemiology has been evolving in recent years with an increased awareness of viral respiratory pathogens since the introduction of respiratory pathogen panels. However, epidemiological and clinical data on pneumonia due to co-infection are lacking.

Methods

A single-center retrospective analysis of mechanically ventilated adult patients treated in critical care units from January to October 2018 was performed on patients with one or more pathogen identified via microbiological testing of a bronchoalveolar lavage (BAL) sample. SOFA and APACHE II scores at the time of admission to the critical care unit and SOFA the day the of BAL were obtained, along with ICU length of stay, duration of ventilation, and pathogens. Associations between categorical variables and co-infection status were assessed using Chi-Square tests, Fisher exact tests, and t-tests. Differences in counts of days between coinfection status groups were analyzed by generalized linear models.

Results

140 bronchoalveolar lavage samples met inclusion criteria, of which 31 were determined to have co-infection with two or more pathogens identified. Of the two methods used to obtain BAL samples, co-infection was found in a higher proportion of patients undergoing bronchoscopic BAL as compared with blinded (35.6% vs. 7.5%; P < 0.0001). Patients with co-infection were determined to be statistically more likely to require a longer duration of mechanical ventilation (P = 0.03); however, there was no difference overall seen in 30 day mortality rate (23.4% vs. 19.57%; P = 0.61).

Conclusion

Co-infection is a significant risk factor for a prolonged duration of mechanical ventilation compared with patients with single pathogen pneumonia. In addition, the use of bronchoscopic BAL appears to be a significant factor in identifying higher rates of co-infection compared with blinded. Although our study failed to demonstrate a significant difference in mortality rates, this could have occurred due to the small sample size.

Disclosures

All authors: No reported disclosures.
2228. Treatment of Community-Acquired Bacterial Pneumonia (CABP) in Patients with Diabetes: Outcomes from a Global Phase 3 Study of Delafloxacin (DLX)
Authors: Kaidashev Igor , Nitu Mimi , Popescu Monica , Lawrence Laura , Quintas Megan , Li Yang , Cammarata Sue
Published: October 2019

Background

Delafloxacin (DLX) is an IV/oral anionic fluoroquinolone with no QT restrictions. It is approved for the treatment of serious skin infections including those due to MRSA and Gram-negative pathogens. A Phase 3 trial of patients with CABP was recently completed comparing DLX to moxifloxacin (MOX), including patients with diabetes (DM).

Methods

Multicenter, randomized, double-blind trial of adults with CABP with at least 2 clinical symptoms; physical signs; and radiographic evidence of pneumonia. Patients were randomized 1:1 to DLX or MOX treatment for 5–10 days. Patients received a minimum of 3 days of IV treatment, then were switched to oral at MD discretion. Key endpoints were the Early Clinical Response (ECR) at 96 ±24h and the investigator assessment of response at Test of Cure (TOC) 5–10 days after last dose in the Intent to Treat population. Clinical success was defined as complete or near resolution of signs and symptoms and no further antibiotics needed per investigator assessment.

Results

131 DM patients were randomized. Patient characteristics: 59% male; mean age 66 (26% ≥ age 75); 40% PORT class IV/V; 29% multi-lobar pneumonia. Bacterial pathogens were identified in 59% at baseline. Patients received treatment ~8.5 days. DLX was comparable to MOX in patients with DM, with response at ECR 90% DLX vs. 88.5% MOX [1.5 (95% CI -9.6, 13.2)] as well as Clinical Success at TOC 87.1% DLX vs. 86.9% MOX [0.3 (95% CI −11.6, 12.7)]. The overall % of DM patients with at least one treatment-related adverse event (AE) was 18.6% DLX and 11.7% MOX. The most frequent treatment-related adverse events were gastrointestinal in nature including diarrhea seen in 6 DLX and 2 MOX patients.There were 3 DLX and 2 MOX deaths of patients with DM during the study (up to Day 28), unrelated to treatment. There were no cases of C diff in these patients. There were no reports of hypoglycemia on DLX. There was one discontinuation of treatment due to a related AE in each treatment group.

Conclusion

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

Disclosures

All authors: No reported disclosures.
2270. Initial Treatment Selection Among Patients with Recurrent Pseudomonas aeruginosa (PSA) Infections (Infxs): Does Prior PSA Antibiotic Susceptibility Results Effect Subsequent Empiric Treatment Decisions?
Authors: Puzniak Laura , Gupta Vikas , Dillon Ryan J , Yu Kalvin , Murray John , Lodise Thomas
Published: October 2019

Background

Resistance to commonly used anti-pseudomonal β-lactams (AP-BLs) like piperacillin/tazobactam (TZP), meropenem (MER) and cefepime (CEF) among patients (patients) with PSA infx is increasing. To minimize receipt of DAT among patients with PSA infxs, clinicians need to consider the patient’s risk of having a PSA infx that is NS to commonly used AP-BLs. A well-described risk factor for having a NS AP-BL PSA infx is recent history of an NS AP PSA infx. This study evaluates the likelihood that a patient with a PSA infx receives an AP-BL that was found to be NS on a prior PSA culture.

Methods

This was a multi-center (n = 239), retrospective cohort analysis using the 2018 data from the BD Insights Research Database (Becton, Dickinson and Company). Inclusion criteria: age ≥ 18 years; hospitalized; PSA infx (index PSA infx); occurrence of a PSA infx ≤ 1 year of index PSA infx (post-index PSA infx); and received treatment for the post-index PSA infx for ≥ 24 hours. Frequency of NS to ≥ 1 AP-BL (MER, TZP, or CEF) for the index PSA infxs was calculated. Among patients with an index PSA infx that was NS ≥ 1 AP-BL, the number of patients who received an AP-BL for the post-index PSA infx that was NS on the index PSA infx was determined.

Results

During study period, 16,062 patients had a PSA infx and 2,386 (14.9%) of patients had a post-index PsA infx. The most common culture sites for the index and post-index PSA infxs were respiratory and urine. The most commonly prescribed AP-BL for the post-index PSA infx were TZP (41.9%), CEF (40.3%), and MER (30.8%). In total, 1,026 (43%) of patients had an index PSA infx that was NS to ≥1 AP-BL. Among the 1,026 patients with an index PSA infx that was NS to ≥1 AP-BL, 902 (88%) patients received an AP-BL as initial therapy for the post-index PSA infx and 558 (62%) patients received an AP-BL that was reported as NS on the index PSA culture.

Conclusion

The findings highlight the importance of considering prior PSA culture and susceptibility data when selecting initial antibiotic therapy for patients who present with a suspected or documented PSA infx and have a history of a prior PSA infx. Patients with history of a PsA infx that was NS to ≥1 AP-BL may benefit from initial use of novel AP-BL therapies.

Disclosures

All authors: No reported disclosures.