bluuebunny/crossref_metadata_2025 huggingface dataset:
2072. Do ID and Non-ID Clinicians Agree on IV to PO Switch Criteria? Results from Phase I of the INForming IV to ORal MEdication Report (INFORMER) Project
Authors: Bosma Rachael , Haj Reem , Dai David , Mamdani Muhammad , Young Michaelia , Gough Kevin , Langford Bradley J , Downing Mark , Schwartz Kevin L , Topolovec-Vranic Jane , Mccall Michele , Taggart Linda R , Leung Elizabeth
Published: October 2019

Background

Converting intravenous (IV) antibiotics to an oral (PO) route is an important stewardship activity to reduce patient harm, including extravasation, thrombophlebitis, and catheter-related infections. The INFORMER Project aims to develop a “smart” electronic tool to streamline IV to PO conversion in eligible patients using an algorithm derived from patient-level data. In designing the algorithm, we noted significant clinician subjectivity in reviewing PO eligibility criteria. To support algorithm development and frontline clinician buy in for future e-tool use, an initial step of our project explored agreement level for IV to PO switch between general internal medicine (GIM) vs. ID clinicians.

Methods

A convenience sample of GIM patients (tertiary teaching hospital) were reviewed in a 4-month pilot. Patients were still on the ward and received a target IV antibiotic (fluoroquinolone, sulfamethoxazole/trimethoprim, clindamycin, metronidazole, linezolid, fluconazole, voriconazole, azithromycin). To mimic real-time decision-making, clinicians (MD and PharmDs) retrospectively assessed IV to PO eligibility of the last IV antibiotic dose on admission for (1) GI/absorption, (2) clinical stability and (3) global review (but not given specific thresholds/criteria). Agreement level was compared for ID vs. non-ID reviews.

Results

Overall, 52 patients’ IV to PO eligibility was assessed by multiple clinicians; 5 GIM teams and 6 ID MDs or PharmDs participated. ID vs. GIM respective assessment of Global eligibility was 61% vs. 48% (agreement in 71% of cases). ID vs. GIM assessment of acceptable absorption was 82% vs. 67%; acceptable clinical stability was 64% vs. 62% (Fig 1). Clinician comments were reviewed to identify algorithm improvements and areas for frontline education.

Conclusion

Our results are consistent with prior data suggesting up to 40–50% of patients may be eligible for IV to PO conversion, even at institutions that have IV to PO protocols. Our data also shows that overall, ID clinicians were more likely to assess a patient as ready for PO antibiotics vs. non-ID clinicians. Our findings are important as understanding cases of non-agreement and obtaining GIM consensus for tool utility are important for our next step, assessing INFORMER implementation on realtime IV to PO conversion rates.

Disclosures

All authors: No reported disclosures.
2082. Evaluation of Outpatient Parenteral Antimicrobial Therapy (OPAT) Processes and Outcomes Among Patients Within an Integrated Health System
Authors: Brown Brittany , Dilworth Thomas J , Cook Margaret , Brummitt Charles F
Published: October 2019

Background

Successful management of outpatient parenteral antimicrobial therapy (OPAT) optimizes outcomes and reduces cost. We examined (i) local OPAT processes and outcomes, (ii) whether OPAT constraints favoring once daily antibiotics promoted suboptimal therapeutic choices, and (iii) whether these data could drive OPAT improvements.

Methods

Patients ≥ 18 years of age who received > 48 hours of OPAT at five infusion centers within a single health-system from January 1, 2018 to March 1, 2018 were eligible for review. The following patient- and treatment-level data were collected: age, gender, drug allergies, laboratory studies and frequency, OPAT indication, infection source, pathogen(s), antibiotic sensitivities, antibiotic therapy and duration, electronic order set used, prescriber specialty, evidence of failed prior oral or intravenous (IV) therapy and IV access type. The primary outcome was OPAT success: the clinical resolution of the infection without relapse within 30 days of antibiotic therapy completion. Secondary outcomes included change in antibiotic therapy due to lack of clinical improvement, adverse drug reactions and IV access complications. A sub-analysis of patients who received daptomycin and/or ertapenem was also performed. OPAT practice was compared with 2018 Infectious Diseases Society of America OPAT guidelines (Norris et al. Clin Infect Dis. 2019;68(1):e1-e35).

Results

A total of 108 patients were evaluated. Patient demographics, treatment and outcomes are shown in Table 1. The most common OPAT indications were bone/joint, bacteremia and skin infection. Third-generation cephalosporins, carbapenems and daptomycin were most commonly prescribed. In 34.3% and 24.2% of daptomycin and ertapenem cases, respectively, β-lactam therapy could have been utilized. Assessment of prior failed antibiotic therapy, patient allergies and pathogen-site pairing found 28.7% of patients were eligible for oral therapy upon OPAT initiation.

Conclusion

Several components of our local OPAT aligned with current guidelines. Initial OPAT patient selection may benefit from added scrutiny. Given the high volume of once daily antibiotics administered for convenience there is an internal opportunity to facilitate multi-daily infusions.

Disclosures

All authors: No reported disclosures.
2084. Implementation of a Diagnostic Stewardship Algorithm by Bedside Nurses to Reduce Unnecessary Urinary Cultures in Hospitalized Adult Patients
Authors: Fabre Valeria , Pleiss Ashley , Demko Zoe , Sick-Samuels Anna , Hicks Lauri , Neuhauser Melinda M , Srinivasan Arjun , Cosgrove Sara E , Cosgrove Sara E
Published: October 2019

Background

Urine cultures (UCx) are often ordered in patients without symptoms of urinary tract infection. A pilot study was conducted to assess the impact of a nurse-driven UCx diagnostic stewardship intervention for adult inpatients.

Methods

We interviewed eight nurses to determine the feasibility of a nurse-driven UCx stewardship intervention. Based on their feedback, an algorithm with appropriate indications for UCx was developed (Figure 1) and approved by physicians and nurses for piloting on a 24-bed medicine unit at The Johns Hopkins Hospital. UCx orders/100 patient-days (PD) were trended with statistical process charts in the intervention and a control unit. Nurses used the algorithm to guide discussions with ordering providers and to suggest instances where UCx may be unnecessary (“intervention”). Nurses were educated on an antibiotic (abx) use safety and appropriate testing during live sessions prior to algorithm implementation. Two study team members reviewed all UCx ordered in the intervention unit 12 months before and 6 months after the intervention for appropriateness based on algorithm criteria. Feedback on UCx order appropriateness and case-based discussion were provided to nurses via in-person meetings post intervention. Data were compared using the χ 2 or the Mann–Whitney test as appropriate. The rate of UCx orders before and after the intervention were compared using a standard incident ratio (IRR).

Results

With algorithm implementation, the mean rate of UCx orders/100 PD decreased from 2.7 to 1.8 (39% decrease) in the intervention unit (IRR 0.61, 95% confidence intervals (CI) 0.45–0.82, P = .16). Mean UCx order rates in the control unit were 2.49 and 2.99, respectively (Figure 2). Characteristics of patients reviewed for appropriateness were similar between the two study periods: median age 63 (IQR 39, 74) vs. 56 (IQR 45, 76), female sex 65% vs. 61%, on hemodialysis 7% vs. 11%, urinary catheter present 20% vs. 29%. The proportion of inappropriate UCx decreased from 59% (98/165) to 50% (32/64) (P = 0.16). There were 8 and 1 cases of asymptomatic bacteriuria inappropriately treated in the pre- and post-intervention periods, respectively (42 and 7 abx days).

Conclusion

With the appropriate training and tools, nurses can steward UCx and reduce unnecessary testing and abx use

Disclosures

Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant.
2095. Antimicrobial Stewardship (ASP) in Rural and Critical Access Hospitals (CAHs) Using TeleStewardship® Services
Authors: Ased Sumaya J , Horne John , Vivekanandan Renuga , Destache Christopher J
Published: October 2019

Background

MDstewardship® is a physician-owned company that uses TeleStewardship® services, which consist of telephone and HIPPA-compliant teleconferencing and texting, to provide rural and critical access hospital (CAH) ASP services, ensuring facilities remain compliant with Joint Commission ASP requirements. MDstewardship® also provides monthly webinars to all participating hospital personnel for continuing education. Webinars are live, interactive, and contain topics based on IDSA guidelines. MDstewardship® personnel discuss antibiotics with the hospital staff using a HIPPA-compliant secure audio-video feed, phone conference, or secure-text. CAH pharmacists discuss the antibiotics currently being given in their institution and MDstewardship® personnel provide further ASP recommendations. ASP recommendations are provided by MDstewardship® clinically-trained infectious disease pharmacists and infectious disease physicians, and are communicated to on-site pharmacists or directly with providers.

Methods

MDstewardship® is active with many rural CAHs in Nebraska, and over 20 hospitals nationally. Here we report our ASP results for 10 CAHs in Nebraska from August 2018 to April 2019. A total of 401 ASP recommendations were given over that time.

Results

The top three most common infectious diseases diagnoses involving recommendations were UTI (16.7%), pneumonia (15.2%), and bacteremia (13.7%). Most common ASP interventions included alternative therapy (15.7%), additional therapy (13.7%), oral step-down therapy (12.7%), and further laboratory monitoring (12.5%). Additional daily antimicrobial stewardship assistance includes: development of hospital protocols, order-sets, antibiograms and guideline adherence. Total acceptance of ASP recommendations averages > 90%. Reimbursement is based on a contract over 12 months.

Conclusion

The use of TeleStewardship® services allow CAHs to have 24/7 infectious disease specialist and clinically trained antimicrobial stewardship pharmacist support with a high number of interventions and a high acceptance of recommendations. The goal of this program is to give the right antibiotic, right dose, for the right duration, for each patient.

Disclosures

All authors: No reported disclosures.
2096. System-Wide Multi-Pronged Approach Leads to Successful Reduction of Fluoroquinolone Use Across a Large Health System
Authors: Sebastian Danielle , Daragjati Florian , Saake Karl , Fakih Mohamad G
Published: October 2019

Background

Overuse of fluoroquinolones has been associated with increased rates of Clostridioides difficile infections, MRSA, and resistant Gram-negative infections due to selective pressure on normal flora. In addition, the FDA has issued several safety alerts regarding systemic use of fluoroquinolone antibiotics due to concerns for serious adverse events and antimicrobial resistance. Considerable variability in the utilization of this antibiotic class across the system resulted in a system-wide initiative to reduce inappropriate prescribing.

Methods

A national initiative included the integration of system-wide approved adult criteria for use into electronic health record order sets and pharmacy clinical decision support systems. System-wide education on the initiative involved learning modules, education toolkits and webinars. Fluoroquinolone utilization rates were reported monthly to help facilities determine the success of initiatives to improve performance.

Results

The fluoroquinolone criteria for use were integrated into several disease-specific order sets system-wide to include: pneumonia, acute exacerbation of COPD, chronic bronchitis, sepsis, acute pyelonephritis, and skin and soft-tissue infection. The learning modules were assigned to all acute care pharmacists resulting in 1,783 completions. Education toolkits were utilized by antimicrobial stewardship teams for provider education. A significant reduction in fluoroquinolone utilization rates, defined by days of therapy (DOT) per 1000 patient-days, was seen across 94 facilities (Figure 1). This resulted in a 45.84% reduction in fluoroquinolone rates from 2017 (56.96, 95% CI 56.72, 57.21) to 2018 (30.85, 95% CI 30.66, 31.04).

Conclusion

Developing and implementing a multi-pronged approach to maximize the effective use of fluoroquinolones can result in significant reductions in utilization across a diverse health system.

Disclosures

All authors: No reported disclosures.
2101. Impact of “Code Sepsis” on Antimicrobial Utilization at an Academic Medical Center
Authors: Kang Minji , Torriani Francesca J , Sell Rebecca , Abeles Shira
Published: October 2019

Background

Balancing antimicrobial stewardship with sepsis management is a challenge. At our academic medical center, a “Code Sepsis” was implemented as a nursing driven initiative to improve early recognition and management of sepsis. Per protocol, Code Sepsis is activated in patients who meet two or more systemic inflammatory response syndrome (SIRS) criteria due to a suspected infection to allow for early implementation of the sepsis bundle, which includes laboratory testing, fluid resuscitation, and antibiotic administration (Figure 1). We analyzed the impact that Code Sepsis had on antimicrobial use among hospitalized patients over a six month period.

Methods

We reviewed the electronic medical records of hospitalized patients with Code Sepsis activation between January 1, 2018 and June 30, 2018 to determine whether antibiotics were “escalated” or “not escalated.” Among patients who had antibiotic escalation, escalation was classified as “indicated” or “not indicated” (Figure 2). A logistic regression model was used to identify characteristics, SIRS or organ dysfunction criteria predictive of indicated antimicrobial escalation.

Results

Code Sepsis was activated in 529 patients with antibiotics escalated in 247 (47%) and not escalated in 282 (53%) (Table 1). Among patients whose antibiotics were escalated, 64% (152) had an indication. In 36% (89), escalation was not indicated as Code Sepsis was due to a suspected noninfectious source, known infectious source already on appropriate antimicrobials, or a suspected infectious source in which diagnostic results had already shown the absence of the infection (Figure 2). Odds of indicated antibiotic escalation increased with the number of SIRS and organ dysfunction criteria (Table 2).

Conclusion

In our efforts to improve sepsis outcomes, we focused on early recognition (Code Sepsis) and intervention (sepsis bundle). However, our Code Sepsis inadvertently led to antibiotic overutilization. By refocusing Code Sepsis on early recognition of severe sepsis and septic shock, we hope to optimize resource utilization and improve patient outcomes.

Disclosures

All authors: No reported disclosures.
2111. Anidulafungin vs. Micafungin Treatment in Adult Patients with Candidemia: A Retrospective Study of Single-Center Experience
Authors: Suh Jinwoong , Yeon Kim Jeong , Seung Chung You , Lee Hojin , Bean Kim Sun , Kyung Yoon Young , Wook Sohn Jang , Ja Kim Min , Hun Kim Jong
Published: October 2019

Background

Candidemia is one of the fatal causes of nosocomial infection, requiring prompt recognition and treatment. Echinocandins are recommended for the treatment of invasive candidiasis and candidemia. Although similar clinical efficacy and safety are well known between caspofungin and micafungin, there are few studies comparing micafungin and anidulafungin. The objective of this study was to evaluate the clinical efficacy and safety between micafungin and anidulafungin treatment for adult patients with candidemia.

Methods

This retrospective cohort study was performed on adult candidemia patients diagnosed from January 2006 through December 2018 at a tertiary medical center, Seoul, South Korea. The study subjects included adult patients ≥19 years with candidemia who were only treated with micafungin or anidulafungin for more than 3 days. Baseline and clinical characteristics were reviewed through electrical medical records. Liver function was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Hepatotoxicity was deﬁned as the elevation of more than CTCAE grade 1 and severe hepatotoxicity was deﬁned as the CTCAE grade 3 or higher elevations.

Results

A total of 98 patients with candidemia was treated with micafungin (n = 46, 46.9%) or anidulafungin (n = 52, 53.1%). In the univariate analysis, there were no significant differences in age, sex, source of candidemia, and comorbidities between the micafungin and anidulafungin groups. Although the clearance time of candidemia after echinocandin treatment was shorter in the anidulafungin than in the micafungin (5.64 ± 2.79 vs. 8.06 ± 5.30 days, P = 0.009) group, there was no significant difference in terms of clinical response (51.9% vs. 46.7%), mycological response (76.9% vs. 67.4%), and mortality (54.3% vs. 55.8%) between these two groups. The overall incidence of hepatotoxicity was similar. Also, there was no difference in the development of hepatotoxicity or severe hepatotoxicity between micafungin and anidulafungin groups for patients with normal baseline liver function test(LFT) and abnormal baseline LFT.

Conclusion

Our results suggest that clinical efficacy and hepatotoxicity may be similar between micafungin and anidulafungin treatment for adult patients with candidemia.

Disclosures

All authors: No reported disclosures.
2114. Correlation Between Antifungal Consumption and the Distribution of Candida Species in a Hospital in Colombia
Authors: Arboleda Harold T , Moreno German A , Ordonez Diaz Karen M
Published: October 2019

Background

In recent years, a shift toward non albicans Candida infections has been described. An increase in the prescription of antifungals has been attributed as the cause of this change, but this issue has not been evaluated in Colombia.

Methods

The distribution of Candida spp. over an 11-year period 2007–2018 were extracted of the software WHONET 5.6. Antifungal drug consumption was measured as the number of defined daily doses (DDD)/100 patient-days over a 6-year period 2012–2018. Spearman’s coefficient was performed to find a correlation between antifungal consumption and distribution of Candida species.

Results

A total of 811 non-duplicate isolates of Candida spp. were included. An increase in the frequency of isolates was observed in the period 2013–2016 (Figure 1). The highest number of isolates were collected from the intensive care unit (ICU) (35.6%) followed of medical ward (22%). Non albicans Candida predominated (58%) in the period evaluated. The shift toward non albicans Candida was presented in 2015 (Figure 2). A non-homologous distribution of albicans vs. non-albicans was noted between ICU and general ward (P = 0.026). 152 (18.7%) isolates were recovered from blood. C. parapsilosis was the most commonly species identified in the blood cultures of ICU in contrast to C. albicans in general ward (Figures 3 and 4).

Intravenous fluconazole was the main antifungal prescribed in ICU (mean 0.094 DDD/100 PD). Oral fluconazole was the principal antifungal prescribed in a medical-surgery ward (mean 0.021 DDD/100 PD) and oncology unit (mean 0.429DDD/100 PD). None of the correlations between antifungal consumption and recovery of non albicans species reached a statistical significance.

Conclusion

The shift toward non albicans Candida is possible even in the presence of a low consumption of antifungals. This finding suggests the possibility of other contributing factors such as cross transmission and microbiome alteration.

Disclosures

All authors: No reported disclosures.
2120. Minimum Inhibitory Concentration Distribution of Fluconazole against Cryptococcus Species and the Fluconazole Exposure Prediction Model
Authors: Chesdachai Supavit , Rajasingham Radha , Nicol Melanie R , Meya David , Bongomin Felix , Abassi Mahsa , Skipper Caleb , Kwizera Richard , Rhein Joshua , Boulware David
Published: October 2019

Background

Fluconazole is lifesaving for the treatment and prevention of cryptococcosis; however, optimal dosing is unknown. Initial fluconazole doses of 100 mg to 2000 mg/day have been used. Prevalence of fluconazole non-susceptible Cryptococcus is increasing over time, risking the efficacy of long-established standard dosing. Based on current minimum inhibitory concentration (MIC) distribution, we modeled fluconazole concentration and area under the curve (AUC) relative to MIC to propose a rational fluconazole dosing strategy.

Methods

First, we conducted a systematic review using the MEDLINE database for reports of fluconazole MIC distribution against clinical Cryptococcus isolates. Second, we utilized fluconazole concentrations from 92 Ugandans who received fluconazole 800 mg/day coupled with fluconazole’s known pharmacokinetics to predict plasma fluconazole concentrations for doses ranging from 100 mg to 2000 mg via linear regression. Third, the fluconazole AUC above MIC ratio were calculated using Monte Carlo simulation and using the MIC distribution elucidated during the systemic review.

Results

We summarized 21 studies with 11,094 clinical Cryptococcus isolates. MICs were normally distributed with geometric mean of 3.4 mg/mL, median (MIC50) of 4 mg/mL, and 90th percentile (MIC90) of 16 mg/mL. The median MIC50 trended upwards from 4 mg/mL in 2000–2012 to 8 mg/mL in 2014–2018. Predicted sub-therapeutic fluconazole concentrations (below MIC) would occur in 38% with 100 mg, 20% with 200 mg, and 8% with 400 mg. AUC/MIC ratio > 100 would occur in 53% for 400 mg, 74% for 800 mg, 84% for 1200 mg, and 88% for 1,600 mg.

Conclusion

Currently recommended fluconazole doses may be inadequate for cryptococcosis. Further clinical studies are needed for rational fluconazole dose selection.

Disclosures

All authors: No reported disclosures.
2150. Detection and Characterization of Viral and Bacterial Pathogens in Tonsillar Tissues of Children Undergoing Tonsillectomy
Authors: Wang Huanyu , Xu Li , Everhart Kathy , Leber Amy
Published: October 2019

Background

The diagnosis of upper respiratory infections is commonly made using nucleic acid amplification technologies for viruses and bacteria. The impact of latency and colonization are not often appreciated. We aimed to detect viruses and bacteria present in tonsil and adenoid tissues from children during the absence of acute infection symptoms.

Methods

Remnant tonsil and adenoid tissues were obtained from children undergoing tonsillectomy procedures. Nucleic acids of viruses and bacteria were detected using laboratory developed PCRs targeting Epstein–Barr virus (EBV), Adenoviruses (AdV), human herpes virus 6 (HHV6), human enteroviruses (HEV), Group A streptococcus (GAS), Kingella kingae (KKN), Staphylococcus aureus (SA), Streptococcus pneumoniae (SPN), Arcanobacterium haemolyticus (AHE), Fusobacterium necrophorum (FNE), Mycobacterium pneumoniae (MPN) and Neisseria meningitidis (NM). The genogroup of AdV and the type of HHV6 were determined as well. Demographics, clinical presentation and detection rates of these viruses and bacteria were analyzed.

Results

During the study period (April 2018 and March 2019), 239 samples were collected from patients <18 years with an average age of 5.1 years. More male subjects than female subjects were included (57.7% vs. 42.3%). Most of the patients underwent tonsillectomy due to adenotonsillar hypertrophy (93.3%). Thirty (12.5%) also had a history of tonsillitis, 224 (93.7%) sleep apnea, 36 (15.1%) otitis media, 35 (14.6%) Eustachian tube dysfunction and 46 (19.2%) had other conditions. The detection of the pathogens among each age group is presented in Table 1. The seasonal distributions of virus positivity are shown in Figure 1.

Conclusion

The detection rates of each virus and bacterium in the tonsillar tissues from children absent of acute infection symptoms vary in each age group and fluctuate among seasons. In the molecular era when syndromic real-time multiplex PCR kits can provide sensitive and rapid results for a wide range of pathogens, it is important to understand the meaning of detection and differentiate between an infection and colonization or latency.

Disclosures

All authors: No reported disclosures.
2159. Accurate Carbapenem Susceptibility Testing Within 5–6 Hours
Authors: Stern Eric , Flentie Kelly , Spears Benjamin , Chen Felicia , DaPonte Kayla , Baker Kristin , Esmurria Ariela , Floyd Fred , Liu Jamie , Pasangulapati Vamsee , Plunkett Niall , Puff Derek , Purmort Nate , Reilly Patrick , Reynolds Andy , Shah Hemal , Somers Mark , Vacic Aleksandar , Briscoe Matthew , Varner Kenny , Chao Alan , Miller Noah , Quon Meghan , Jie Chen Jun , Clancy Mark , Persing Alana , Jane Ferraro Mary , Rosenberg David C
Published: October 2019

Background

Patients infected with multi-drug-resistant (MDR) pathogens may experience long delays to targeted therapies due to the incomplete antimicrobial menus and/or breakpoints tested on current commercial antimicrobial susceptibility testing (AST) systems. Detection of carbapenem resistance poses a challenge to rapid, accurate, minimum inhibitory concentrations (MIC) determinations because some resistant organisms may be inhibited by a carbapenem antibiotic until sufficient carbapenemase production has been achieved and traditional AST platforms must wait to make MIC calls. More accurate carbapenem MICs can be determined by implementing a carbapenemase test alongside rapid AST.

Methods

We demonstrate a novel, proprietary test to detect carbapenemase production that enables rapid MIC testing for carbapenem antibiotics. The test is processed in parallel with the Selux next-generation phenotyping (NGP) AST method, enabling rapid, <6-hour, accurate MIC determinations. The carbapenemase assay utilizes high concentrations of intact bacteria. After 3 hours of incubation, a fluorescent pH indicator is read spectroscopically. The solution pH is lowered by carbapenemase-mediated imipenem degradation and is indicative of enzyme activity.

Results

This assay accurately identifies carabapenemases across multiple enzyme classes and bacterial species. Figure 1 shows the accuracy and speed of NGP AST at determining MICs for representative isolates from the FDA-CDC antimicrobial resistance bank compared with results from overnight broth microdilution (BMD). To date, over 100 challenge strains of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii have been tested with no very major errors and an average time-to-result of 5.3 hours.

Conclusion

By incorporating a rapid, on-board carbapenemase activity assay, the NGP AST platform rapidly delivers accurate carbapenem results. Combined with NGP’s comprehensive antibiotic menus, this platform will therefore ensure prompt delivery of personalized antibiotic therapies for all patients, including those infected with MDROs, and enable streamlined antibiotic stewardship coordination.

Disclosures

All authors: No reported disclosures.
109. Clinical Characteristics and Outcomes of Staphylococcus aureus Bacteremia From a Biliary Source
Authors: Yang Eunmi , Bae Seongman , Seo Hyeonji , Cho Eunbeen , Park Su-Jin , Sung Heungsup , Kim Mi-Na , Jung Jiwon , Jae Kim Min , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Hee Woo Jun , Soo Kim Yang , Pil Chong Yong
Published: October 2019

Background

Staphylococcus aureus can cause various types of infection, but involvement of biliary tract is rare. There were only few case reports and no clinical studies. We assessed the clinical characteristics and outcomes of S. aureus bacteremia from a biliary source (biliary SAB) in a large cohort of SAB patients and compared the cases with those of catheter-related SAB.

Methods

We performed a matched case–control study within a prospective observational cohort of patients with SAB at a 2,700-bed tertiary hospital. All adult patients with SAB were observed for 12 weeks from July 2008 to July 2018. Biliary SAB was defined as the case of S.aureus isolated from blood culture with appropriate clinical biliary infection symptoms (fever, abdominal pain, or jaundice) and signs (abdominal tenderness or liver enzyme elevation with obstructive pattern). Biliary SAB cases were matched 1:3 to control patients with catheter-related SAB based on age, gender, ward, and case year.

Results

A total of 1,818 patients with SAB were enrolled in the entire cohort, and 42 (2%) were biliary SAB. Among patients with biliary SAB, 32 (76%) had solid tumor involving pancreaticobiliary tract or liver, 30 (71%) had biliary drainage stent, 14 (33%) were biliary procedure-related infection, and 24 (57%) had recent broad-spectrum antibiotics exposure (Table 1). When biliary SAB patients were compared with 126 patients with catheter-related SAB, they were significantly more likely to have community-onset SAB, solid tumor, and lower APACHE II score; and less likely to have metastatic infection (P = 0.03) (Table 2). Biliary SAB, solid tumor, and a high Charlson comorbidity index were associated with 12-week mortality. In multivariate analysis, biliary SAB (aOR, 5.5; 95% CI, 2.47–12.25) and a high Charlson comorbidity index (aOR, 1.32; 95% CI, 1.12–1.54) were independent risk factors for 12-week mortality.

Conclusion

Biliary SAB was relatively rare and developed mainly in pancreaticobiliary cancer patients and in recent broad-spectrum antibiotic users. High mortality was probably attributable to underlying cancers. When biliary tract infection caused by S. aureus is clinically suspected, early aggressive treatment for SAB should be considered.

Disclosures

All authors: No reported disclosures.
2164. Activity of Fosfomycin (FOF) and Frequency of Nonsusceptible Inner Colonies During Susceptibility Testing of an International Collection of Clinical Pseudomonas aeruginosa (PA) Isolates
Authors: Smith Elizabeth C , Brigman Hunter V , Anderson Jadyn C , Emery Christopher L , Bias Tiffany E , Landersdorfer Cornelia B , Bergen Phillip J , Hirsch Elizabeth B , Hirsch Elizabeth B
Published: October 2019

Background

FOF has been used clinically for the treatment of PA infections in the absence of established interpretive criteria. A recent study identified a low frequency of nonsusceptible inner colony mutants during disk diffusion (DD) testing of Escherichia coli; however, the frequency of this phenomenon in PA isolates is not well characterized. We sought to determine FOF activity against an international collection of PA isolates and the frequency of inner colony mutants observed during Etest and DD testing.

Methods

Minimal inhibitory concentration (MIC) values were determined for a convenience collection of 109 PA ([70/94] 64.2% MDR) isolates from 4 institutions in the United States and Australia. MIC testing was conducted in duplicate on separate days utilizing agar dilution (AD), broth microdilution (BMD), DD, and Etest as recommended per Clinical and Laboratory Standards Institute (CLSI). CLSI E.coli interpretive criteria (≤ 64 mg/L susceptible) were used for MIC interpretations. The proportion of isolates containing inner colonies was determined using DD and Etest. Inner colony mutants were subcultured and retested using BMD with comparison to the parent isolate MICs.

Results

FOF MICs varied widely and ranged from 1024 mg/L with MIC50/MIC90 values of 64/256 (AD), 64/512 (Etest), and 64/256 (BMD) mg/L. Using E. coli criteria, susceptible/resistant rates were: 60.5/17.4% for AD; 60.5/22.0% for Etest; 86.2/7.3% for DD; and 53.2/17.4% for BMD. Inner colonies were frequently observed in 38.5% and 35.8% of DD and Etest inhibition zones, respectively. After repeat testing, mutant MIC values ranged from 64 to > 1024 mg/L and a majority (85.9%) had MIC values ≥ 512 mg/L.

Conclusion

Observed MIC values of this (64% MDR) collection varied widely with MIC50/90 values commonly at or above the E. coli susceptibility breakpoint. Inner colony mutants were frequently observed and highly resistant. Whole-genome sequencing is currently underway for a subset of parent/mutant pairs to determine whether specific genetic alterations are attributed to the increased MICs. Based on these results, caution should be warranted in extrapolating E. coli breakpoints to other organisms, and treatment of PA with FOF should be further evaluated.

Disclosures

Elizabeth B. Hirsch, PharmD, Merck: Grant/Research Support, Research Grant; Nabriva Therapeutics: Advisory Board; Paratek Pharmaceuticals: Advisory Board.
2179. Detection of Group A Streptococcus in the Saliva of Children Presenting With Pharyngitis Using the cobas®LIAT® PCR System
Authors: DeMuri Gregory P , Wald Ellen R
Published: October 2019

Background

CLIA waived polymerase chain reaction (PCR) has recently become available as a point of care test for Group A Streptococci (GAS) in individuals presenting with pharyngitis, enabling rapid and accurate diagnosis. However, swabbing the pharynx results in discomfort and is often dreaded by young children which may result in poor quality sampling.

Objective

In order to assess the viability of saliva as a sample specimen for GAS, this study compared saliva samples with pharynx swabs of children with sore throat, using swabs inoculated by children sucking on them as they would a lollipop in the context of newly available very sensitive techniques.

Methods

We enrolled children ages 5–15 years presenting with sore throat and known to have a positive rapid streptococcal antigen detection test (RADT) performed on a posterior pharyngeal swab, at the discretion of the primary care provider. The RADT used was the SureVue® (Fisher Scientific) system. A second swab was obtained by having the child suck on the swab in the anterior mouth for 30 seconds and a third swab was obtained from the posterior pharynx. PCR was performed on these two additional swabs using the cobas®LIAT® (Roche) system according to the manufacturer’s instructions.

Results

Seventeen children were enrolled in the study between January and April 2019. The mean age of enrollment was 9.6 years (range 6–15). By design all children were known to have a positive RADT for GAS. The LIAT posterior pharynx swab was positive in all 17 subjects. In addition, the LIAT saliva swab was positive in all 17 subjects.

Conclusion

In this small pilot study, there was 100% concordance between the RADT for GAS and both the posterior pharyngeal and saliva swab using the cobas®LIAT® PCR system. Performing saliva swabs will result in less discomfort and distress to children who are tested for GAS. Further study is needed to determine the sensitivity and specificity of saliva swabs for the detection of GAS in children presenting with acute pharyngitis.

Disclosures

All authors: No reported disclosures.
2183. Survival Impact and Clinical Predictors of Anaerobic Bloodstream Infection
Authors: Hsieh Ronan , Yo Chia-Hung , Liu Cheng-Heng , Galvis Alvaro , Hsieh Yueh-Cheng , Huang Huai-Hsuan , Hsu Tzu-Chun , Lee Chien-Chang
Published: October 2019

Background

Few controlled studies are available for the outcome and risk factor analysis of anaerobic bloodstream infection (BSI). We conducted a cohort study to identify the clinical predictors and survival impact of anaerobic BSI as compared with aerobic BSI.

Methods

Consecutive emergency department patients in a tertiary medical center with laboratory confirmed BSI between 2015 and 2016 were prospectively enrolled. We compared demographics, comorbidity, and sources of infection between anaerobic and aerobic BSI. We then constructed a multivariable logistic regression model to identify independent risk factors for anaerobic BSI. The survival impact of anaerobic BSI was evaluated by propensity score-matched analysis.

Results

We identified 1,166 episodes of BSIs during the 2-year study period, of which 61 (5.2%) were anaerobic BSI. Clinical variables predicted anaerobic BSI with moderate discrimination (optimism corrected C statistic = 0.75). Significant predictors included metastatic cancer (OR 6.03, 95% CI 2.78–13.09), intra-abdomen infection (OR 3.92, 95% CI 1.47–10.45), liver abscess (OR 2.65, 95% CI 1.26–5.62), skin and soft-tissue infection (OR 2.40, 95% CI 1.13–5.08) as the positive predictors. Urinary tract infection (OR 0.15, 95% CI 0.04–0.62), diabetes mellitus (OR 0.38, 95% CI 0.18–0.78), or thrombocytopenia (OR 0.33, 95% CI 0.18–0.60) were identified as the negative predictors of anaerobic BSI. Anaerobic BSI were not associated with worse prognosis in either adjusted (HR 1.08, 95% CI 0.68–1.72) or PS-matched analysis (HR 1.50, 95% CI 0.61–3.67).

Conclusion

Anaerobic BSI accounted for a significant proportion (approximately 1 in 20) of community-onset BSI. Clinical predictors identified in this study may help guide the prescription of empiric anti-anaerobe antibiotics. The apparent adverse outcome associated with anaerobic BSI may be explained by the underline comorbidity, high-risk infection site, and inadequate initial antibiotics.

Disclosures

All authors: No reported disclosures.
2201. Cost of Antimicrobial Use Against Upper Respiratory Infection in Japan
Authors: Tsuzuki Shinya , Kimura Yuki , Ishikane Masahiro , Kusama Yoshiki , Ohmagari Norio
Published: October 2019

Background

Antibiotics are often inappropriately prescribed for treating upper respiratory infection (URI) patients in ambulatory care settings. In Japan, a previous study estimated physicians prescribed antibiotics in about 30% of URI cases. However, trends of prescription behavior and additional costs of inappropriate antibiotic use in URI cases are still not clear in Japan. The present study’s main objective was to clarify the amount of additional cost owing to inappropriate antibiotic prescription for URI, and the recent trend.

Methods

We conducted a retrospective observational survey using longitudinal claims data spanning 2013–2016, obtained from the Japan Medical Data Center Co., Ltd. (JMDC) Claims Database, which contains anonymous claim data on 5.1 million (for 2013–2016) corporate employees covered by the employees’ health insurance plan (Social insurance), and their family members <65 years old. Six physicians specialized in infectious disease assessed the appropriateness of antibiotic prescription based on the ICD-10 code in the database. The total additional cost of antibiotic prescription for URI at the national level was estimated by weighting corresponds to the age-structured population data, from the healthcare payer perspective. Costs of treatment for adverse events and of antimicrobial resistance caused by inappropriate antibiotic prescription were not taken into consideration.

Results

The total annual cost of antibiotic prescription for URI was estimated at US$423.6 (95% confidence interval: 416.8–430.5) million in 2013, $340.9 (335.7–346.2) million in 2014, $349.9 (344.5–355.3) million in 2015, and $297.1 (292.4–301.9) million in 2016.

Conclusion

Although a decreasing trend was observed, the annual cost of antibiotic prescription for URI potentially imposes a substantial economic burden in Japan.

Disclosures

All authors: No reported disclosures.
2204. Microbiology of Pneumonia Due to Co-Infection in the ICU: Impact of Host Immune Status
Authors: Zelus Casey , Blaha Michael , Marcelin Jasmine R , Marcelin Jasmine R , Cawcutt Kelly , Cawcutt Kelly , Kalil Andre C , Samson Kaeli
Published: October 2019

Background

Pneumonia epidemiology is increasingly showing the presence of co-infection due to the utilization of emerging diagnostic testing modalities such as multiplex polymerase chain reaction (PCR) panels. However, the prevalence and clinical significance of co-infection with respect to host immune status remain unclear.

Methods

A single-center retrospective analysis of mechanically ventilated adult patients treated in critical care units from January to October 2018 was performed on those with positive microbiological analysis of a bronchoalveolar lavage (BAL) sample. Host immune status and microbiological analyses were obtained including PCR and culture testing. Categorical variables and co-infection or immunocompetent status were assessed using Chi-Square, Fisher exact tests, or t-tests. REDCap was utilized for data abstraction and SAS software version 9.4 was used to perform all analysis.

Results

Of the 139 BAL samples that met inclusion criteria, 107 and 32 were obtained from immunocompetent and immunocompromised hosts, respectively. There was no statistical difference found between the frequency of co-infection detected by BAL culture with respect to host immune status. Immunocompetent patients had a higher proportion of positive bacterial cultures compared with immunocompromised (76.7% vs. 43.8% respectively, P = 0.0004). There was no significant difference seen with frequency of fungal or acid fast bacilli cultures between the two groups. Analysis of the microbiologic data obtained (figures) revealed different pathogens according to host immune status.

Conclusion

Pneumonia due to co-infection in critically ill, mechanically ventilated immunocompromised hosts occurs at a similar frequency regardless of host immune status, however different microbiological patterns emerge. Interestingly, patients who were not immunocompromised had a higher proportion of positive bacterial cultures compared with those who were immunocompromised. Comparative analysis of the other pathogen types may also reveal differences in detection rates if sample size is increased. Clinically, this may help guide efficient use of microbiological testing among patients based on immune status.

Disclosures

All authors: No reported disclosures.
2205. Clinical Burden of Pneumococcal Disease in US Adults Aged 65 Years and Above with Chronic or Immunocompromising Conditions
Authors: Deb Arijita , Johnson Kelly D , Ou Wanmei
Published: October 2019

Background

The presence of chronic and immunocompromising conditions is associated with a disproportionately high risk of developing pneumococcal disease at older ages. The objective of this study was to quantify the risk of all-cause pneumonia (ACP) and invasive pneumococcal disease (IPD) in older US adults aged 65 years and older with underlying medical conditions.

Methods

A retrospective observational study was conducted using the Humana claims database. The study cohorts were identified at January 1 of each calendar year of observation from 2012 to 2017 and comprised adults aged 65 years and older with continuous enrollment for at least one year before and at least one year after January 1 of each year. For each yearly cohort, medical conditions were identified during the one year before each calendar year and episodes of ACP and IPD were identified during the corresponding 1-year follow-up period from January 1 to December 31. Individuals were stratified into 3 groups: those without any medical conditions of interests (healthy), those with chronic conditions (at-risk) and those with immunocompromising conditions (high-risk). Rate of ACP or IPD was expressed as the number of cases per 100,000 person-years and the rate ratio (RR) was expressed as the rate of pneumococcal disease of patients with medical conditions divided by the rate of pneumococcal disease in healthy adults.

Results

Of the 10,766,827 adults included in the study, 75% of adults had an underlying medical condition linked to an increased risk of pneumococcal disease. In adults with at-risk conditions, rates of ACP and IPD were 3.1 and 3.6 times the rate in healthy adults, respectively. In adults with high-risk conditions, rates of ACP and IPD were 4.1 and 5 times the rate in healthy adults, respectively. Rate of pneumococcal disease increased substantially with the addition of medical conditions: RR for ACP and IPD increased from 2.1 and 2.2, respectively, in adults with one at-risk conditions to 4.8 and 6.2, respectively, among adults with 2 or more at-risk conditions.

Conclusion

Despite recommendations of universal pneumococcal vaccination in older adults aged 65 years and above in the United States, the burden of pneumococcal disease remains high, particularly among those with chronic and immunocompromising conditions.

Disclosures

All authors: No reported disclosures.
2210. Nasopharyngeal Detection of Streptococcus pneumoniae and Clinical Disease Severity in Children with Community-Acquired Pneumonia (CAP)
Authors: Wook Yun Ki , Juergensen Alexis , Wallihan Rebecca , Desai Ankita P , Alter Sherman J , Ambroggio Lilliam , El-Assal Osama , Marzec Sarah , Florin Todd A , Florin Todd A , Keaton Meghan , Shah Samir S , Leber Amy , Mejias Asuncion , Ramilo Octavio , Ramilo Octavio
Published: October 2019

Background

Streptococcus pneumoniae is the most common pyogenic bacteria associated with CAP in children, but the proportion of cases might be underestimated because of the low sensitivity of current standard diagnostic methods. Nasopharyngeal (NP) carriage of pneumococcus commonly precedes the development of pneumococcal pneumonia, and facilitates pneumococcus interactions with other respiratory pathogens and the host immune response. This study investigated the relationship between pneumococcal carriage and the severity of CAP in children.

Methods

We conducted a prospective, multicenter, observational study for CAP among previously healthy children aged 2 months through 18 years in six children’s hospitals in Ohio. Blood, pleural fluid, and NP swabs were collected for pathogen detection by culture and/or polymerase chain reaction (PCR). S. pneumoniae was quantified in NP swabs by real-time PCR. Patient management followed the standard of care in each study site.

Results

Among 441 children with radiologically confirmed CAP, 156 (35.4%) had no bacterial or viral pathogens identified as etiologic agents. NP pneumococcal carriage rate in this group was 34.6%. Children with CAP and pneumococcal carriage (53/156) were younger (5.9 vs. 9.6 years, P < 0.001) than those with no carriage (103/156). Median neutrophil counts and median procalcitonin concentrations were significantly higher in the pneumococcal carriage group (12,030 vs. 8,370 cells/mm3 and 1.0 vs. 0.5 mg/dl, respectively; P < 0.05 for both) than in the non-carriage group. Children with documented pneumococcal carriage received respiratory support more frequently (50.0% vs. 28.2%, p = 0.012) and had a longer duration of hospitalization (3.5 ± 3.8 vs. 2.1 ± 2.0 days, P = 0.026) than those without pneumococcal carriage. Age was not associated with any of the variables used to assess clinical disease severity.

Conclusion

Pneumococcal carriage was associated with higher inflammatory markers and greater clinical disease severity in children with CAP in whom no pathogens were identified by standard diagnostics. This suggests that NP carriage of pneumococcus in children with CAP may modulate the host immune response and possibly influence clinical disease severity.

Disclosures

Octavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.