bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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

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

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.
2360. Impact of a Two-Step Antimicrobial Stewardship Intervention on C. difficile Infection Diagnosis at an Urban Veteran’s Affairs Medical Center
Authors: Kuhn Ryan T , Johnson Jennifer L , Nelson Virginia , Fitzpatrick Dustin , Ahmad Syed , Whittington Sylvia , Dhar Sorabh
Published: October 2019

Background

C. difficile infection (CDI) is a common healthcare-associated infection and quality measure for hospitals. Diagnosis of CDI is challenging as testing modalities, i.e., nucleic acid amplification test (NAAT), are highly sensitive but cannot differentiate between colonization and infection. Therefore, judicious use of testing is critical to avoid unnecessary diagnosis and treatments.

Methods

This single-center, retrospective chart review evaluated the impact of a two-step diagnostic stewardship intervention on C. difficile diagnosis and use of oral vancomycin in the inpatient setting. For the first step of the intervention, providers were educated on appropriate diagnosis and treatment, and given access to an optional electronic CDI clinical decision support system (CDSS). For the second step of the intervention, the CDI NAAT stand-alone testing option was removed from the lab ordering menu and providers were required to use the CDSS to order testing. Clinical data including bed-days of care (BDOC), total number tests ordered, number of positive tests and use of oral vancomycin was collected for the pre-intervention period (1/1/16 – 3/31/17), post intervention period 1 (April 1, 2017–October 31/18) and post-intervention period 2 (November 1, 2018–March 31, 2019).

Results

Compared with the pre-intervention group, there were no significant differences in the number of total CDI NAATs ordered, positive CDI NAATs or vancomycin DOT/10,000 BDOC in post-intervention group 1. There was a reduction in the number of total CDI NAATs ordered (341 vs. 42 [87.7%]) and the number of positive CDI NAATs (56 vs. 7 [87.5%]) in post-intervention group 2, respectively. When this data were normalized based on bed days of care (BDOC), there were still significant reductions in NAATs ordered and number of positive CDI NAATs (64 vs. 27 [57.8%]; 11 vs. 5, respectively, [54.5%]) and with vancomycin oral DOT/10,000 BDOC (72 vs. 7 [90.3%]) (Table 1).

Conclusion

Provider education and an optional CDSS did not significantly impact CDI NAAT ordering or use of oral vancomycin for CDI. However, implementation of a mandatory CDSS for CDI testing was shown to significantly decrease the number of tests ordered, the number of positive tests, and the use of oral vancomycin.

Disclosures

All authors: No reported disclosures.
2361. Evaluation of a 2-Step Testing Algorithm for Clostridioides difficile Infection
Authors: Zuccaro Patricia , Son Andrea , Conti Jennifer , Hecker Michelle
Published: October 2019

Background

Clinical data describing use of a multistep algorithm for diagnosis of Clostridioides difficile infection (CDI) is limited. In June 2018 we implemented a 2-step testing algorithm in which PCR testing (Aries® assay) is performed for all specimens followed by EIA toxin testing (TOX A/B QUIK CHEK® assay) when PCR is positive. We sought to describe outcomes for patients with PCR+/EIA+ vs. PCR+/EIA− results. Outcomes evaluated included frequency of CDI treatment, retesting and retreatment within 3 months, and investigator determined categorization of C. difficile results by an investigator blinded to the EIA result.

Methods

A retrospective cohort study was performed on a random sample of 85 unique patients with a PCR+ stool sample from July 2018 through December 2018. Demographic and clinical data were abstracted from the medical record during the index encounter and for 3 months thereafter. Based on predetermined criteria, index encounter results were categorized as representing probable, possible, unlikely, or indeterminate cases of symptomatic CDI.

Results

For the 85 study patients, 42%, 27%, and 31% were tested in the inpatient, outpatient, and ED/urgent care settings. Twenty-seven patients (32%) were EIA+, all of whom received CDI treatment. Fifty-eight (68%) were EIA-, of which 79% received treatment. Of the 12 EIA- patient who did not receive treatment two had retesting within 3 months; one of whom subsequently tested EIA+ and was treated and the other tested PCR-. At least 1 C. difficile test was repeated within 3 months in 48% of EIA+ and 33% of EIA- patients. Based on repeat testing CDI treatment was prescribed for 12% of EIA+ subjects and for 11% of EIA- subjects. For the EIA+ patients, 70%, 19%, 7%, and 4% were classified as probable, possible, unlikely and indeterminate cases of symptomatic CDI when compared with 38%, 34%, 22%, and 5% for EIA- patients.

Conclusion

During the first 6 months of a 2-step testing algorithm, we found that patients with EIA- test results were frequently treated for CDI and that 72% of EIA- cases were classified as probably or possibly having symptomatic CDI. Further study is needed to determine whether patients with EIA- results categorized with probable or possible symptomatic CDI would improve without CDI treatment.

Disclosures

All authors: No reported disclosures.
2366. PCR Followed by Toxin EIA for the Diagnosis of C. difficile Infection
Authors: Zhang Yu , Mohadjer Kiya , McCombs Amy , Thompson Jessica
Published: October 2019

Background

In June 2017 for the diagnosis of Clostridioides difficile infection (CDI), Renown Health transitioned from utilizing polymerase chain reaction (PCR) to a two-step algorithm of PCR followed by toxin enzyme immunoassay (EIA) if PCR was positive. Providers were encouraged to forgo treatment in patients that were PCR-positive and EIA-negative as recent literature suggests this may indicate colonization rather than infection. The purpose of this study was to assess the impact of implementation of the two-step algorithm for the diagnosis of CDI on antibiotic usage and patient outcomes.

Methods

This was a retrospective quasi-experimental study of adult inpatients at Renown Regional and South Meadows Medical Centers that were PCR positive before and after implementation of a two-step algorithm for the diagnosis of CDI. The pre-implementation period was defined between May 8, 2016 and May 7, 2017, and the post-implementation period was May 8, 2017 to May 7, 2018. Patients were excluded if they were admitted to a pediatric ward, tested for CDI at an outside facility, or if results were available following discharge. The primary outcome was inpatient days of metronidazole and non-parenteral vancomycin per PCR positive patient. Secondary outcomes included defined daily doses of therapy, proportion of untreated patients, time to resolution of diarrhea, all-cause in-hospital mortality, 30-day recurrence, all-cause 30-day readmission, length of stay, and 30-day CDI-related complications. CDI-related complication was a composite of ICU care, megacolon, ileus, surgical intervention. It was calculated that 242 patients were required to achieve at least 80% power to detect a 30% difference in antibiotic days between pre- and post-implementation of two-step C. difficile testing. Wilcoxon two-sample test was used for continuous data, and χ 2 or Fisher exact test were used for categorical data.

Results

See figures.

Conclusion

Incorporation of C. difficile toxin EIA to PCR for the diagnosis of CDI resulted in a significant reduction in non-parenteral vancomycin and metronidazole days of therapy. Patient outcomes were not adversely affected by the addition of toxin EIA. The results suggests that toxin EIA may help differentiate between C. difficile colonization and active infection.

Disclosures

All authors: No reported disclosures.
2372. PCR Ribotype and Antimicrobial Susceptibility of Clostridioides (Formerly Clostridium) difficile in Korea
Authors: Hoo Jeon Cheon , Mi Wi Yu
Published: October 2019

Background

Clostridioides difficile infection is a leading cause of healthcare-associated diarrhea. The epidemiology and characteristics of C. difficile vary geographically. We performed toxin enzyme immunoassay (EIA), toxigenic gene analysis, antimicrobial susceptibility tests (AST), and PCR ribotyping to elucidate the characteristics of C. difficile in Korea.

Methods

Between July 2017 and June 2018, C. difficile was prospectively isolated in 128 specimens from the culture of 1,182 unduplicated specimens. Seventy-five stool specimens with a positive toxin EIA between July 2016 and June 2017 were also included. We performed PCR for the tcdA and tcdB genes on these isolates, and AST and PCR ribotyping on the isolates with a positive toxin EIA.

Results

Older patients tended to have a higher rate of positive toxin EIA and positive cultures than did younger patients. Ribotype 018 was predominantly identified (48.6%), followed by ribotype 014/020 (9.9%), and ribotype 002 (8.3%). All of A-B+ isolates were either ribotype 017 or B-2. Ribotypes 017, 018, and B-2 showed high resistance to various antibiotics. In contrast, ribotypes 002, 014/020 and C-4 demonstrated low resistance rates, except that to moxifloxacin in ribotype 002. Clindamycin and erythromycin showed a positive correlation. Most of the isolates resistant to rifampicin or tetracycline showed a high MIC to both erythromycin and clindamycin.

Conclusion

Ribotype 018, which is highly transmissible and resistant to various antimicrobial agents, is predominant in Korea. Ribotype 002 has also been increasing in prevalence in Korea.

Disclosures

All authors: No reported disclosures.
2378. Corticosteroid Use Prevents Primary Clostridioides difficile Infection in the Setting of Broad-Spectrum Antibiotic Use Among Hospitalized Patients
Authors: Carlson Travis J , Wilcox Melissa F , Theriault Sarah G , Alnezary Faris S , Gonzales-Luna Anne J , Zasowski Evan J , Garey Kevin W
Published: October 2019

Background

Clostridioides difficile is the most common pathogen causing healthcare-associated infections in the United States and a Centers for Disease Control and Prevention urgent threat-level pathogen. The pathophysiology of C. difficile infection (CDI) involves neutrophil invasion of the colon associated with an inflammatory response. Previous case–control studies investigating an anti-inflammatory corticosteroid (CS) effect on CDI risk demonstrated conflicting results but were unable to control for antibiotic use. We hypothesized that CS use would decrease the risk of CDI in a well-matched, high-risk population.

Methods

This nested case–control study included hospitalized patients admitted to a single quaternary care hospital in the Texas Medical Center. The case population included adults who were diagnosed with CDI and received at least one dose of an antibiotic of interest (piperacillin–tazobactam, cefepime, or meropenem) in the 90 days prior to CDI diagnosis. The control population included hospitalized adults who received one of the same antibiotics during their hospital stay but did not develop CDI in the 90 days following their first dose. Patients were excluded if they had a documented history of CDI. CS use was defined as ≥ 20 mg prednisone or equivalent administered in the 48 hours prior to CDI diagnosis (cases) or antibiotic start (controls). The primary study outcome was the development of CDI. A logistic regression model was developed modeling CDI diagnosis as a function of available patient covariates.

Results

A total of 321 patients met the inclusion criteria; 56 patients had a history of CDI, leaving a final study cohort of 265 patients (104 cases and 161 controls). Antibiotic days of therapy were significantly higher in the control group (8 vs. 6 days; P = 0.02). The odds of CDI diagnosis were lower among patients administered CS (OR, 0.17; 95% CI, 0.08–0.38; P < 0.001), which remained protective in the multivariable model after adjusting for age, gender, and invasive GI surgery within 6 months.

Conclusion

We observed an association between CS use and decreased risk of developing primary CDI in hospitalized patients receiving broad-spectrum antibiotics. Future studies are needed to delineate the dose and duration of CS needed to realize this effect.

Disclosures

All authors: No reported disclosures.
2411. One Dose Vancomycin Prophylaxis for In-Hospital Clostridioides difficile - Associated Disease
Authors: Papic Neven , Stemberger Maric Lorna , Dusek Davorka , Vince Adriana
Published: October 2019

Background

Clostridioides difficile - associated disease (CDAD) is the most common cause of healthcare-associated diarrhea with increasing prevalence and mortality rates. Recent reports suggest that prophylactic administration of vancomycin or fidaxomicin might reduce in-hospital CDAD incidence. The aims of this study were to examine whether primary oral vancomycin prophylaxis (OVP) reduces the in-hospital incidence of CDAD in elderly patients treated with systemic antibiotics and its impact on 90-day readmission rate.

Methods

This single-center, retrospective cohort study included 484 patients ≥ 65 years who received antimicrobial therapy for ≥ 24 hours and were hospitalized for ≥ 72 hours during a 24-month period. Patients diagnosed with CDAD within the first 48 hours of hospitalization were excluded. OVP group received ≥ 1 dose of vancomycin 125 mg once per day.

Results

Patients within OVP group (122; 25.2%) had higher age adjusted Charlson comorbidity index (CCI) (8; IQR 6–10 vs. 6; 5–8), were more often hospitalized within 3 months (62; 50.8% vs. 121; 33.4%), more commonly received piperacillin/tazobactam (60; 49.2% vs. 81; 22.4%) and carbapenems (27; 22.1% vs. 43; 11.9%) with longer duration of antibiotic therapy (14; 10–20 vs 10; 10–14 days). CDAD was diagnosed in 3 (2.5%) patients in OVP, compared with 45 patients (12.4%, p = 0.0011) in control group. In logistic regression analysis CCI > 6 (OR 3.54; 95% CI 1.79–6.87), OVP (0.19; 0.06–0.57), nursing home residency (4.10; 2.40–7.02), carbapenems (3.14; 1.60–6.15) and piperacillin/tazobactam (5.43; 2.87–10.14) were associated with CDAD. In this cohort, 28 (23.7%) patients from OVP and 69 (21.7%) patients from control group had 90-day readmission. 6 patients in OVP (4 new episodes) and 21 (14 new episodes) in control group were admitted for CDAD. Only CDAD during index hospitalization was associated with 90-day readmission (HR 4.60; 95% CI 1.93–10.96).

Conclusion

Primary OVP was highly effective in reducing the risk of in-hospital CDAD in elderly patients treated with systemic antimicrobial therapy. Prospective studies with follow-up are needed to define long-term efficacy and potential risks of this strategy.

Disclosures

All authors: No reported disclosures.
2414. Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in High-Risk Patients
Authors: Johnson Steven W , Priest David H , Brown Shannon V
Published: October 2019

Background

Studies suggest oral vancomycin prophylaxis may be effective in preventing Clostridioides difficile infection. These studies are limited by their retrospective design, reliance on local clinical practice patterns, lack of intervention standardization, and limited risk stratification. We sought to evaluate the effectiveness of oral vancomycin for the prevention of healthcare facility-onset CDI (HCFO-CDI) in high-risk patients.

Methods

We conducted a randomized, prospective, open-label study at Novant Health Forsyth Medical Center in Winston-Salem, North Carolina between October 2018 and April 2019. Admitted high-risk patients (defined as: ≥ 60 years of age, hospitalized ≤ 30 days prior to the index hospitalization and received systemic antibiotics during that prior hospitalization and currently receiving systemic antibiotics) were randomized 1:1 to either oral vancomycin (dosed at 125 mg once daily while receiving systemic antibiotics and continued for 5 days post completion of systemic antibiotics [OVP]), or no prophylaxis. The primary endpoint was incidence of HCFO-CDI. Secondary endpoints included incidence of community-onset healthcare facility-associated CDI (CO-HCFA-CDI), development of VRE colonization after receiving OVP, and adverse effects and cost of OVP.

Results

A total of 100 patients were evaluated, 50 patients in each group. Baseline and hospitalization characteristics were similar in each group. No incidents of HCFO-CDI were diagnosed in the OVP group compared with 6 (12%) in the no prophylaxis group (P = 0.03). CO-HCFA-CDI was not observed in either group. No patients developed new VRE colonization with only 1 patient reporting mild gastrointestinal side-effects to OVP. A total of 600 doses of OVP were given during the study, with each patient receiving an average of 12 doses. Total acquisition cost of OVP was $728.25, $60.69 per patient.

Conclusion

OVP was highly effective in preventing HCFO-CDI. OVP was well tolerated with no apparent risk for VRE colonization. Further prospective investigation is warranted to determine the impact and cost-effectiveness of routine use of OVP in high-risk patients.

Disclosures

All authors: No reported disclosures.
2416. Effect of Sequential Universal Bleach Cleaning and Best Practice Alerts on Clostridioides difficile Infection Rates
Authors: Gand Kari , Helmin Derrek , Johnson Shawnda , Kline Susan E , Galdys Alison
Published: October 2019

Background

A gap analysis prompted consideration of expanded bleach disinfection beyond rooms housing patients in isolation for Clostridioides difficile infection (CDI) and emphasis on CD testing stewardship at the University of Minnesota Medical Center (UMMC), a tertiary care center spanning two campuses in close proximity with adult patients on the East Bank (EB), adult and pediatric patients on West Bank (WB).

Methods

An electronic best practice advisory (BPA) went live in April 2018 on both the EB and WB (Figure 1). The BPA first discourages CD testing in the event of a prior positive within 10 days or a prior negative within 7 days. Second, the BPA discourages CD testing in patients with fewer than 3 loose stools in a 24 hour period, who have received laxatives in the last 48 hours, or who lack CDI symptoms (fever > 38C, abdominal pain, or leukocytosis > 11,000). Providers can bypass the BPA based on clinical judgment; those who override the BPA are provided just-in-time education via email.

Following a successful pilot in three wards, the EB Environmental Services (ES) team expanded the use of bleach to include all terminal cleaning regardless of isolation status in June 2018 (Figure 1). Daily cleaning on the EB was excluded from universal bleach utilization, as were daily and terminal cleaning on the WB.

CD testing throughout the study period occurred via polymerase chain reaction (PCR) of the toxin B gene. ES performance, assessed by adenosine triphosphate (ATP) bioluminescence testing, and hand hygiene rates were unchanged throughout the study period.

Results

Adult-only hospital-onset (HO)-CDI rates decreased during the study period on both hospital campuses, with the EB exhibiting a greater decrease, (Fig 1), while community-onset (CO) and community-onset healthcare facility associated (CO-HCFA) rates remained steady during the study period (Fig 3). Whole-house (adult and pediatric) CD testing was largely unchanged while the proportion of tests triggering the BPA decreased (Fig 2).

Conclusion

Universal bleach utilization during terminal cleaning combined with an electronic BPA were associated with decreased adult HO-CDI rates. However, the BPA did not impact CD testing rates, suggesting that decreased HO-CDI rates may be unattributable to testing stewardship.

Disclosures

All authors: No reported disclosures.
2427. A Laboratory Simulation and Field Study of Simplified Qualitative and Quantitative Environmental Cultures for Clostridioides difficile
Authors: Curry Scott R , Vanderhorst Aisha , Zhao Yujing , Steed Lisa , Salgado Cassandra
Published: October 2019

Background

Reliable, simple methods to assess environmental contamination with Clostridioides difficile are needed for studies of terminal disinfection effectiveness and transmission of C. difficile from fomites. We compared two novel sampling methods for assessment of C. difficile contamination: (1) isopropanol wipe sampling with broth enrichment (IW), where alcohol wipes are used to sample surfaces followed by immersion in CDBB-TC broth and (2) ethanol-shock hand imprint sampling (HI), where surfaces are sampled by gloved hands moistened with ethanol hand sanitizer followed by imprinting hands on selective agar (CDBA-TC). Both methods allow for sampling of complex surfaces common in hospital environments.

Methods

We performed a laboratory simulation study using six 10-fold dilutions (101–106) of C. difficile spores from two strains sampled from fiberglass surfaces by IW and HI. We then performed a field study of 10 sites in 11 hospital rooms of patients with C. difficile infection (CDI) diagnosed < 48 hours prior to sampling. Results for the HI and IW method were quantitative and qualitative, respectively. We compared room contamination prevalence (total CFU per room by HI and sites positive/total sites per room) to the cycle crossing threshold (CT) from the diagnostic C. difficile PCR test (Cepheid) from the room occupant.

Results

The IW laboratory limit of detection was 101 spores compared with 104 spores for HI. In the field study, IW and HI detected C. difficile contamination in 9/11 (82%) rooms at 22/110 (20%) sites and 5/11 (45%) rooms at 22/110 (20%) sites, respectively (Table 1). Six rooms with no detection by the HI method had a lower median number of sites positive per room compared with the 5 rooms with ≥1 cfu (1 vs 6, P < 0.05) (Table 1). The most commonly contaminated sites were linens (53%), call bells (43%), toilets (40%), blood pressure cuffs (40%), over-bed tables (38%), and bedrails (30%) (Table 2). Higher tcdB CT was associated with a lower total room contamination prevalence (Figures 1 and 2).

Conclusion

Our data suggest that the IW method is more sensitive for detection of C. difficile in the hospital environment, but the HI method offers quantitation. The prevalence of hospital room contamination for CDI patients appears to correspond with their toxin burden as estimated by PCR.

Disclosures

All authors: No reported disclosures.
2439. The role of positive externalities in economic evaluations of new antibiotics: modeling the impact of reduced transmission in healthcare facilities
Authors: Nelson Richard , Samore Matthew H , Jernigan John A , Slayton Rachel , Toth Damon
Published: October 2019

Background

Positive externalities - beneficial spillover effects enjoyed by individuals who are not the primary consumers of a good - are rarely considered in cost-effectiveness analyses (CEAs) of antimicrobial drugs that could reduce person-to-person transmission of the target pathogen. We developed a compartmental model to simulate the effect of 2 hypothetical antibiotics targeting carbapenem-resistant Enterobacteriaceae (CRE) among hospital inpatients: one that treats bloodstream infections (BSIs) and one that decolonizes carriers. We assessed the contribution of positive externalities to the results of CEAs of these 2 antibiotics in the model.

Methods

Our model tracked patients according to CRE carriage, clinical infection, and detection status. Rates of CRE acquisition depended on transmissibility of carriers in different states and were calibrated to data from long-term acute care hospitals. For the BSI treatment scenario we assumed the new drug would decrease the death rate and transmissibility of patients after CRE BSI onset. For the decolonization scenario we assumed the new drug would increase clearance of CRE carriage after clinical detection. For each scenario, we quantified the drug’s effect on the number of BSIs and deaths among patients receiving the drug (direct effect) and among all patients (total effect, i.e., direct plus indirect effect) compared with usual care. For the CEAs, the effectiveness outcome was life-years (LYs) gained and we assumed the new drug cost of $4,000 per dose and cost of a CRE BSI of $24,788.

Results

For both the BSI treatment and decolonization scenarios, the total effect of introducing the new drug was greater than the direct effect alone, indicating the existence of positive externalities. Relative to usual care, the new drug led to a decrease in incremental cost and an increase in incremental effectiveness (see Figures 1 and 2).

Conclusion

The inclusion of positive externalities in CEAs can have important effects on whether these new antibiotics are deemed cost-effective, due to their potential for interrupting chains of transmission. In our model, the inclusion of these effects reduced the incremental cost and increased the incremental effectiveness of these antibiotics.

Disclosures

All authors: No reported disclosures.
2442. Detection of Prosthetic Hip and Knee Joint Infections Using Administrative Databases – A Validation Study
Authors: Kandel Christopher , Jenkinson Richard , Davey Roderick , Widdifield Jessica , Hansen Bettina , Muller Matthew P , Daneman Nick , McGeer Allison
Published: October 2019

Background

Forming large cohorts to study prosthetic joint infections (PJIs) is a challenge without an existing surgical registry, as is the case in Canada. Administrative databases are an option, yet PJI diagnostic codes are insensitive. There is a need to improve the detection of PJIs from within administrative databases.

Methods

Individuals who had a primary arthroplasty at four hospitals in Toronto, Canada from 2010 to 2016 were identified using Canadian Classification of Health Intervention codes (based on the International Classification of Disease, Tenth Revision). Each re-admission to the same hospital until December 31, 2016 was reviewed for the presence of a PJI. The performance characteristics (sensitivity, specificity, positive and negative predictive values) of combinations of diagnostic and procedure codes when compared with the gold standard of chart review were calculated. The primary outcome was the algorithm that maximized sensitivity and positive predictive value.

Results

27,843 primary arthroplasties were performed with 8595 readmissions, of which 572 involved a PJI. Median follow-up was 1258 days (interquartile range (IQR) 614–1891 days), with median time to first re-admission of 352 days (IQR range 166–725 days). PJI codes exhibited a sensitivity of 0.86 (95% confidence interval (95% CI) 0.83–0.89) and positive predictive value (PPV) of 0.89 (95% CI 0.86–0.92). The best performing algorithm is a combination of a PJI code or joint spacer insertion procedure code or insertion of a peripherally inserted central catheter along with an arthroplasty code (sensitivity 0.90, 95% CI 0.88–0.93 and PPV 0.89, 95% CI 0.86–0.91). Using timing from primary arthroplasty, spacer insertion codes and presence of a subsequent arthroplasty procedure code identified 68% (71/105) of first stage and 74% (108/146) of debridement with joint retention procedures during the first re-admission for a PJI.

Conclusion

Combinations of diagnosis and procedure codes can reliably identify PJIs from administrative databases. Individual orthopaedic procedure codes and timing from primary arthroplasty can inform the surgical procedure performed. This PJI detection algorithm could be used for PJI surveillance and research.

Disclosures

All authors: No reported disclosures.
2447. Impact of Agency-Level Policies and Priorities upon Infection Prevention and Control in the Home Environment: Perspectives of Home Health Staff
Authors: Chastain Ashley , Pogorzelska-Maziarz Monika , Stone Patricia , Shang Jingjing
Published: October 2019

Background

Infection prevention and control (IPC) is becoming a national priority in home healthcare (HHC) industry. However, little is known about the impact of agency-level policies and priorities upon IPC practices in the home environment. This qualitative study aimed to explore: 1) how home health agencies (HHA) are implementing IPC policies, and 2) perspectives of HHC staff on agency-level IPC policies and priorities and how they impact patient care.

Methods

From March to November 2018, we recruited staff from HHAs across the United States to participate in in-depth, telephone interviews. HHAs were purposively sampled based on high or low Quality of Patient Care star rating and other agency characteristics from 2016 Provider of Services and Home Health Compare data. Interviews were conducted with 41 staff from 13 HHAs, including administrators, IPC and quality improvement personnel, registered nurses and home health aides. Interview guides were tailored toward the role of the interviewee. Interview transcripts were coded and themes were identified using content analysis.

Results

Themes included: 1) “Handwashing is our priority”; 2) Innovative approaches to care coordination and IPC; (3) Monitoring staff compliance; and, (4) Opportunities for improvement. Almost all HHC staff described that handwashing was a primary focus of IPC policies and staff education at their agencies. Some staff depicted creative ways that their agency was coordinating patient care among staff who were not always in the office, and also unique approaches to educating staff about IPC policies and practices. Administrators and managers explained the ways that they monitored staff compliance around IPC policies, while nurses and aides described how the monitoring reminded them about proper procedures. Finally, HHC staff mentioned various ways in which care coordination, staff education and compliance could be improved at their agencies; for example, more frequent supervisory visits were perceived as a way to improve compliance with agency policies and practices.

Conclusion

This study increases our understanding of the impact that agency-level IPC policies and practices have upon HHC staff and patient care, in addition to specific approaches to care coordination, staff education and compliance monitoring.

Disclosures

All authors: No reported disclosures.