bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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.
2273. Outcomes of Trimethoprim/Sulfamethoxazole as Definitive Therapy for Urinary Tract Infections with Multi-Drug-Resistant Enterobacteriaceae
Authors: Adhi Fatima , Dubrovskaya Yanina , Cytryn Samuel 
Published: October 2019

Abstract

Background
Trimethoprim/Sulfamethoxazole (TMP/SMX) is not routinely employed for urinary tract infections (UTI) with multi-drug-resistant organisms (MDRO) due to paucity of effectiveness data, concerns regarding inadequate urinary penetration, and risk of adverse effects. We describe our experience with TMP/SMX as definitive therapy for MDRO Enterobacteriaceae (MDRO-E).

Methods
We carried out a retrospective review of patients hospitalized at a tertiary care center and treated with TMP/SMX as definitive therapy for UTI with MDRO-E (as defined by resistance to third-generation cephalosporins in culture). We evaluated rates of overall cure rate (CR), adverse events (AE), recurrence (RC) and reinfection (RI). Repeat growth of same or different pathogen in urine culture (UC) within 30 days of completion of treatment was defined as RC or RI, respectively.

Results
92 patients had 101 episodes of MDRO-E UTIs treated with TMP/SMX as initial (n = 26, 25.7%) or as step-down therapy (n = 23, 77%) after broad-spectrum empiric antimicrobials (ceftriaxone n = 22, cefepime n = 21, piperacillin/tazobactam n = 12, carbapenems n = 6, ciprofloxacin n = 3). 63 (68.5%) patients were 65 years or older. MDRO-E in 10 (9.9%) episodes were also resistant to carbapenems. Empiric therapy was appropriate in 56 (55.5%) episodes. Median duration of treatment was 8.5 (range 3–24) days for all antimicrobials and 7 (range 2–15) days for TMP-/SMX. Overall CR was 100%. RC/RI was seen in 23/101 (22.8%) episodes (RC n = 9; RI n = 14); UC data were available for 20 of which 8/20 (40%) had a TMP/SMX-resistant organism. 4 (3.9%) patients required readmission for a RC/RI UTI. In terms of AEs: 10 (9.9%) episodes of hyperkalemia (median maximum potassium level 4.5 mmol/L, range 2.7–6.4), 3 (2.9%) episodes of acute kidney injury, 5 episodes of Clostridium difficile infection, and 4 (3.9%) readmissions for a RC/RI UTI within 90 days.

Conclusion
Our findings suggest that TMP/SMX can be safe and effective as definitive therapy for ESBL-E UTI. The major AE are hyperkalemia and AKI, the incidence of which is high when TMP/SMX is used in combination with ACEI/ARBs. No clinical factors were found to be predictive of recurrence of reinfection.

Disclosures
All authors: No reported disclosures.
2280. Bloodstream Klebsiella pneumonia Infection and Carbapenem Combination Treatment Regimen in High-Dose Vasopressor-Dependent Septic Shock
Authors: Magira Eleni , Perlikos Fotis , Kokkoris Stelios , Zakynthinos Spyros 
Published: October 2019

Abstract

Background
The clinical effectiveness of the double-carbapenem combination therapy in mechanically ventilated patients with carbapenemase-producing carbapenem-resistant Enterobacteriaceae bloodstream septic shock infection is not well studied.

Methods
Over a 4-year period (2013–2017), critically ill with high-dose vasopressor-dependent septic shock patients due to infections from Enterobacteriaceae were included in a single-center retrospective study. The clinical presentation of septic shock was defined in accordance with the international guidelines. Clinical characteristics and the presence of clinical success by the 3rd-day of treatment and 28-day outcome were evaluated. Clinical success was defined as the complete elimination of the vasopressors along with the absence of bacteria regrowth in blood cultures of Enterobacteriaceae. The combination therapy consisted of 1-hour ertapenem (1 g/day) infusion followed immediately by meropenem (6 g/day) in a prolonged 3-hour infusion. The therapeutic regimen was also included gentamicin (7 mg/kg) once daily for 3 total days because of the severity of shock.

Results
A total of 16 ICU patients with bloodstream infection causing septic shock included in the study. The bacterial strain of Enterobacteriaceae was exclusive of Klebsiella pneumonia isolated after the second week of ICU admission. Antibiotic resistance profile was carbapenem 16/16 (100%), colistin 16/16 (100%), tigecycline 14/16 (87%) aminoglycosides 10/16 (62.5%). Patients were comparable in terms of age, comorbidities, APACHE II score, and presence of concomitant ventilator-associated pneumonia. Klebsiella pneumonia bloodstream infection was catheter-related in 5/16 (31%), and the source was not identified in 11/16 (69%). Overall, complete microbiological eradication of Klebsiella pneumonia regrowth in blood cultures performed 72 h after therapy was observed in 14/16 (87%) patients, and complete shock resolution in 12/16 (75%). Death at day 28 occurred in 5/16 (31%) patients attributable to multiple organ failure.

Conclusion
The double-carbapenem regimen in critically ill patients suffering high-dose vasopressor-dependent septic shock due to bloodstream infections from Klebsiella pneumonia is an effective therapeutic option.

Disclosures
All authors: No reported disclosures.
122. Evaluation of Early Clinical Failure Criteria in Patients with Enterococcus Species Bloodstream Infection
Authors: Powers Caroline , Caulder Celeste , Bouknight Abigail , Ann Justo Julie , Kohn Joseph , Rac Hana , Al-Hasan Majdi , Brandon Bookstaver P 
Published: October 2019

Abstract

Background
Early clinical failure criteria (ECFC) were recently proposed to predict poor clinical outcomes in patients with Gram-negative bloodstream infections (BSI). ECFC are measured between 72 and 96 hours from collection of index blood culture (Table 1). The objective of this study was to evaluate the performance of ECFC in predicting 28-day mortality in patients with Enterococcus spp. BSI.

Methods
This IRB-approved, retrospective, observational cohort study included adult patients hospitalized at Prisma Health–Midlands hospitals from January 1, 2015 to July 31, 2018 with a monomicrobial BSI due to Enterococcus spp. Patients with a previous episode of Enterococcus spp. BSI within one year prior to index culture or those who died within 72 hours were excluded. Multivariate logistic regression was used to examine the association between ECFC and 28-day all-cause mortality. The area under the receiver operating characteristic (ROC) curve was used to measure model discrimination.

Results
A total of 157 patients with Enterococcus spp. BSI were included. Overall, the median age was 66 years, 96 (61%) were men, and 106 (68%) had community-onset BSI. The urinary tract was the most common source of infection (45; 29%), followed by intraabdominal infections (34; 22%). Twenty-eight patients (18%) died within 28 days of BSI. After adjustments for age and Charlson Comorbidity Index, every one-point increase in the ECFC was associated with an 80% increase in the odds of 28-day mortality (OR 1.8, 95% CI 1.3–2.4, P < 0.001). Mortality increased from 4% in patients with ECFC of 0 to 11%, 28%, and 38% as ECFC increased to 1, 2, and ≥3, respectively. The area under ROC curve of ECFC model in predicting 28-day mortality was 0.74 with ECFC of 2 identified as the best cutoff point. Mortality was 8% in patients with ECFC < 2 compared with 33% in those with ECFC ≥2 (P < 0.001).

Conclusion
ECFC demonstrated good discrimination to predict 28-day mortality in hospitalized adult patients with Enterococcus spp. BSI. These criteria may have utility as a stratification or randomization tool in future clinical investigations evaluating optimal antimicrobial treatment duration or effectiveness of intravenous to oral switch therapy in uncomplicated Enterococcus spp. BSI.

Disclosures
All authors: No reported disclosures.
124. Impact of Levofloxacin MIC on Outcomes with Levofloxacin Step-down Therapy in Enterobacteriaceae Bloodstream Infections
Authors: White Melissa , Lenzi Kerry , Dutcher Lauren S , Saw Stephen , Morgan Steven C , Binkley Shawn , Athans Vasilios , Cimino Christo L , Degnan Kathleen , Hamilton Keith W 
Published: October 2019

Abstract

Background
The Clinical and Laboratory Standards Institute reduced the levofloxacin minimum inhibitory concentration (MIC) breakpoint from ≤2 to ≤0.5 mg/L for Enterobacteriaceae in 2019 guidelines. The reduction is based on Monte Carlo simulations for a levofloxacin dose of 750 mg daily. The aim of this study was to determine whether there was a difference in clinical outcomes in the treatment of Enterobacteriaceae bacteremia with levofloxacin step-down therapy retrospectively comparing patients with isolates with low levofloxacin MICs (≤0.5 mg/L) to high MICs (1–2 mg/L).

Methods
This retrospective, two-center cohort study included patients ≥18 years of age with a monomicrobial Enterobacteriaceae bacteremia with a levofloxacin MIC ≤2 mg/L from March 2017 through December 2018. Patients had to have received treatment with ≥3 days of levofloxacin step-down therapy, initial intravenous therapy with an agent active against the isolated organism, and total duration not exceeding 16 days from first negative blood culture. A subset of patients whose isolates had low levofloxacin MICs were randomly selected for comparison to all patients with high levofloxacin MICs in a 3:1 ratio. The primary outcome was a composite endpoint of recurrence and mortality within 30 days of completion of the antibiotic course. Secondary outcomes included post-culture length of stay (LOS) and 30-day readmission rate.

Results
Thirty-three patients with high MIC and 99 with low MIC were included. Urinary source was predominant and occurred in 44% of patients, and Escherichia coli was the infecting organism in 48%. Over 80% of patients experienced source resolution or control. The composite endpoint occurred in 8.1% of the low MIC group and 9.1% of the high MIC group (P = 0.856). Median LOS was 4.9 days (IQR 3.7–8.0) in the low MIC group and 4.3 days (IQR 3.2–6.8) in the high MIC group (P = 0.384), and readmission rate was 17.2% in the low MIC group and 15.2% in the high MIC group (P = 0.787).

Conclusion
There was no between-group difference in the primary outcome of recurrence and mortality, with a low overall event rate and short LOS post-culture. These results suggest that levofloxacin effectiveness may be sustained in patients with MICs of 1 or 2 despite levofloxacin not meeting susceptibility criteria by new definitions.

Disclosures
All authors: No reported disclosures.
2350. Electronic Interventions to Improve Clostridioides difficile Ordering Practices and Incidence: Impact of Soft Stops vs. Hard Stops
Authors: Ross Barbara , Greendyke William G , Zachariah Philip , Simon Matthew , Whittier Susan , Green Daniel A , Westblade Lars , Karp Jeffrey , Gouveia Adam L , Greenberg Yael C , Parameswaran Lalitha , Singh Harjot , Saiman Lisa , Calfee David P , Yoko Furuya E 
Published: October 2019

Abstract

Background
Distinguishing between Clostridioides difficile infection (CDI) and asymptomatic colonization with a PCR-based test can be difficult and can lead to unnecessary antibiotic use, longer lengths of stay and inflated hospital-onset (HO) CDI rates. Additionally, inappropriate testing for CDI complicates this challenge. The Infectious Disease Society of America’s (IDSA) 2018 guidelines discourage CDI testing for patients who received laxatives within 48 hours. Our hospital implemented a two-phase clinical decision support order set (DSOS) to improve appropriateness of CDI testing.

Methods
The DSOS was implemented at a hospital system in New York City (2 large academic medical centers, 2 community hospitals, 1 pediatric hospital: total 2,200 beds). The electronic health record is Allscripts SCM tm. The first iteration of the DSOS required providers to document the indication for CDI testing, as well as a soft stop (SS) pop-up message prompting providers to reconsider testing in patients who received laxatives within 24 hours. The second phase of the DSOS utilized a hard stop (HS) that prevented providers from ordering CDI testing for patients who received laxatives within 24 hours. Providers received a pop-up with IDSA recommendations for CDI testing and contact information for the Clinical Microbiology Laboratory. If testing was still desired, the ordering provider had to discuss the case with a Pathology resident or Infectious Disease specialist before the laboratory staff placed the order. The monthly number of orders and tests sent in the different time periods, pre-SS (April 2016–April 2017), post-SS (May 2017–2019, 2018), and post-HS (November 2018–March 2019), were compared using ANOVA. The National Healthcare Safety Network calculator was used to compare CDI incidence density ratios and SIRs between the three periods.

Results
SS implementation significantly reduced mean monthly orders (18%) and HO-CDI SIR (31%) but SIR remained above national benchmarks. Adding a HS further reduced orders (25%) and SIR (18%) (table).

Conclusion
A DSOS designed to reduce inappropriate CDI testing among patients who received laxatives within 24 hours was associated with a reduction in CDI testing and the CDI SIR. While use of a soft stop reduced CDI testing, the addition of a hard stop was associated with additional significant reductions in the CDI SIR.

Disclosures
All authors: No reported disclosures.
128. Adequacy of Commonly Prescribed Antimicrobials for Empiric Coverage of Gram-Negative Bacterial Pathogens Recovered from the Bloodstream of Patients Attending Emergency Rooms in Canada: Analysis of Data from the CANWARD Study, 2007 to 2018
Authors: Walkty Andrew , Adam Heather , Baxter Melanie , Henni Amina , Lagace-Wiens Philippe , Karlowsky James , Zhanel George 
Published: October 2019

Abstract

Background
Inadequate empiric antimicrobial therapy for Gram-negative bacteremia is associated with adverse clinical outcomes. The purpose of this study was to evaluate the proportion of Gram-negative bacterial isolates recovered from the bloodstream of patients attending Canadian emergency rooms (ERs) that remain susceptible to commonly prescribed antimicrobials.

Methods
Annually from 2007 to 2018, sentinel hospitals across Canada collected bloodstream isolates from patients attending ERs as part of the CANWARD study. Susceptibility testing was performed using broth microdilution as described by CLSI (data analysis limited to Gram-negative bacteria in the top 10 pathogens), with current CLSI breakpoints applied. Extended-spectrum β-lactamase (ESBL)-producing isolates were confirmed using the CLSI disk diffusion method.

Results
Gram-negative bacteria among the top 10 bloodstream pathogens for patients seen at ERs across Canada were: Escherichia coli (n = 2,414), Klebsiella pneumoniae (n = 573), Pseudomonas aeruginosa (n = 211), Proteus mirabilis (n = 119), and Enterobacter cloacae (n = 114). Aggregate susceptibility of these isolates to common antimicrobials was as follows (% susceptible [S]): meropenem 99.4% S, piperacillin–tazobactam 98.5% S, gentamicin 93.3% S, ceftriaxone 88.1% S, ciprofloxacin 81.4% S, TMP-SMX 73.5% S. The most active antimicrobials evaluated vs. E. coli were meropenem (100% S), piperacillin–tazobactam (98.8% S), and ceftriaxone (93.3% S). Ceftriaxone susceptibility among E. coli isolates declined from 95.4% in 2007 to 89.8% in 2018. The average proportion of E. coli isolates that harbored an ESBL enzyme increased from 3.4% in the first three study years to 8.4% in the last three study years. The most active antimicrobials evaluated vs. K. pneumoniae isolates were meropenem (99.7% S), piperacillin–tazobactam (98.8% S), gentamicin (97.7% S), and ceftriaxone (96.9% S).

Conclusion
The most consistently active antimicrobials for empiric treatment of patients at Canadian ERs with Gram-negative bacteremia are meropenem and piperacillin–tazobactam. Ceftriaxone susceptibility among E. coli has declined over the last 12 years, mostly related to an increase in ESBL-producing isolates.

Disclosures
All authors: No reported disclosures.
2354. Report at Your Own Risk! Diagnostic Stewardship of Clostridioides difficile PCR Results from Syndromic Diarrhea Panel and Implications for Patient Outcomes
Authors: Wadskier Montagne Francis G , Cowman Kelsie , Guo Yi , Bartash Rachel , Szymczak Wendy , Levi Michael , Weston Gregory , Nori Priya 
Published: October 2019

Abstract

Background
We implemented a syndromic gastrointestinal pathogen panel (GIP) in May 2018, for rapid diagnosis of infectious diarrhea. GIP Clostridioides difficile polymerase chain reaction (PCR) results were suppressed due to concerns about oversensitivity. All positive (+) GIP and standard of care (SOC) C. difficile results were reviewed to understand C. difficile epidemiology and clinical outcomes.

Methods
Between May and December 2018, an audit of all adult patients with C. difficile (+) GIP results was conducted. Stewardship team obtained daily GIP results, reviewed patient charts, recommended a confirmatory SOC test, isolation, and treatment as indicated. Patients were classified as true C. difficile infection (CDI) with diarrhea and toxin or PCR positivity (Figure 1). We also reviewed GIP (+)/SOC negative (−) tests, and GIP (−)/SOC (−) tests (control group). GIP (+) patients with no confirmatory SOC test were excluded from the analysis. A multivariable logistic regression model was used to compare CDI at 3 months among groups.

Results
We reviewed 274 patients with a GIP C. difficile (+) result (Table 1). Seventy-one (26%) had no SOC sent. Of positive SOCs, 45 patients (37%) were positive by toxin A/B enzyme immunoassay (EIA), and 77 (63%) by PCR only (Figure 2A). There were 2153 total SOC tests sent, of these 332 (15%) were positive; 130 (39%) by toxin, and 202 (61%) by PCR only (Figure 2B). Mortality and 30-day re-admission were not significantly different between groups (Table 2). CDI rates within 3 months were not significantly different between GIP (+) only and control group (P = 0.11). In contrast, those with SOC (+) tests had more true CDI within 3 months, compared with controls (P < 0.001) (Table 2).

Conclusion
Forty percent of patients analyzed with GIP (+) C. difficile result were (−) by SOC test, suggesting that true CDI was not present in these patients. The percentage of toxin vs. PCR only (+) results from all the GIP positive patients mirrors that of all SOC (+) tests, indicating that the majority of CDI patients at our institution are PCR (+) only. Our results suggest that an additional PCR-based test may potentially over-report colonization as true infection. We strongly support diagnostic stewardship of C. difficile results within syndromic gastrointestinal panels.

Disclosures
All authors: No reported disclosures.