bluuebunny/crossref_metadata_2025_split huggingface dataset:
2419. Timing of Secondary Prophylaxis Against Clostridium difficile Infection After Antibiotic Exposure
Authors: Szela Joel , Hanna Angy , Sims Matthew 
Published: October 2019

Abstract

Background
Clostridium difficile infection (CDI) is the most common nosocomial infection, and is increasing. The major risk for CDI is antibiotic (abx) use. We have previously shown that secondary prophylaxis with vancomycin decreases CDI relapse in patients with recent CDI given abx to treat another infection. The median time to relapse after use of abx was 3 days. In an effort to further elucidate the best way to employ secondary prophylaxis against CDI, we examined all patients with CDI in our institution in 2016 and timing of relapse as related to another exposure to abx and the success of prophylaxis relative to the timing and the duration of prophylaxis.

Methods
All patients positive by PCR for C difficile at our institution in 2016 were examined for receipt of abx within 3 months of a positive PCR. The relapse rates for all patients, patients who received abx with or without secondary prophylaxis, and patients who did not receive abx were calculated. Timing of the relapse from the prior CDI and from receipt of abx were determined as was impact of prophylaxis, particularly in patients who relapsed despite prophylaxis.

Results
1748 patients were identified, representing 2181 episodes of CDI. The relapse rates and timing based on prior CDI, receipt of additional abx prior to relapse, and use of prophylaxis are shown in Table 1.
Prophylaxis decreased the overall relapse rate from 19.2% to 11.6%. Time to relapse in patients who relapsed despite prophylaxis was significantly longer indicating prophylaxis was having an effect. The failure appears dependent on when prophylaxis was started relative to abx and how long prophylaxis was given relative to abx.

Conclusion
Prophylaxis is effective in preventing relapses in patients given abx after CDI however the timing and duration of prophylaxis significantly impacts the effectiveness. The majority of CDI relapses after abx occur within 3 days and can be prevented by prophylaxis. Relapses that occur after 3 weeks appear unrelated to the use of abx and are not preventable through prophylaxis. Failures of prophylaxis within the first 1 week are likely related to starting prophylaxis too late after abx and failures that occur between 1 and 3 weeks after abx are likely related to ending prophylaxis too early.

Disclosures
All authors: No reported disclosures.
2428. Whole-genome Sequencing to Determine Clostridium difficile Transmission
Authors: Madigan Victoria M , Carter Glen , Buising Kirsty , Howden Benjamin , Marshall Caroline 
Published: October 2019

Abstract

Background
Clostridium difficile is a major problem in healthcare institutions due to its substantial attributable morbidity, mortality and costs. Although traditionally recognized as a nosocomial infection, there is increasing evidence that hospital-based transmission may not be as common as previously thought. Whole-genome sequencing (WGS) has superior discriminatory ability than other previously used techniques for C. difficile typing. This study aimed to investigate whether WGS could help to elucidate C. difficile transmission patterns at The Royal Melbourne Hospital (RMH).

Methods
All C. difficile isolates (N = 138) identified in patients admitted to RMH from November 1, 2015 to October 31, 2016 had molecular typing performed by WGS, multilocus sequence typing (MLST) and PCR ribotyping. Clinical epidemiological data were collected for each episode so that patient locations could be examined together with molecular typing information to determine putative transmissions in the hospital.

Results
After combining molecular and clinical epidemiology, a picture of diverse C. difficile emerged. Only 7 (6%) of isolates appeared to have been transmitted from other hospital patients, according to combined WGS and patient location data. However, both PCR ribotyping (33%) and MLST (44%) had significantly higher proportions of putative transmissions in this cohort.

Conclusion
This finding has significant implications for the Infection Prevention team as efforts toward prevention of C. difficile infection may need to be redirected away from the current focus on prevention of nosocomial transmission. Future studies are needed to broaden understanding of C. difficile transmission dynamics so that other sources can be identified and targeted for intervention.

Disclosures
All authors: No reported disclosures.
2429. Whole-genome Sequencing of Healthcare-Onset C. difficile Infection (HO-CDI) Cases Shows Widespread Presence of Antimicrobial Resistance Genes
Authors: Hyun Shin Jae , Viana da Silva Costa Deiziane , Parikh Hardik , Barry Katie E , Mathers Amy J , Warren Cirle 
Published: October 2019

Abstract

Background
Clostridioides difficile infection (CDI) is the most common pathogen to cause healthcare-associated infections. Unlike some other bacterial pathogens antimicrobial treatment is seldom based on culture with susceptibility testing with infrequent surveillance for antimicrobial resistance. We have evaluated healthcare-onset CDI (HO-CDI) for both transmission and antimicrobial resistance emergence.

Methods
We identified cases of HO-CDI diagnosed by PCR within a 3 month period (October 1/2018–December 31/2018) at University of Virginia Health System with overlapping stays in the same inpatient units with other HO-CDI. Chart review of all cases was performed. C. difficile was cultured from stool, then DNA was extracted and underwent sequencing on Illumina Miseq platform. Antimicrobial resistance genes were screened using NCBI’s AMRFinder tool from the de-novo assembled contigs using SPAdes. All the C. difficile isolates underwent antibiotic susceptibility testing.

Results
Eleven patients were identified with overlapping stays from 5 units. Mean age was 64 years and 63.6% were female. 36.3% of cases were severe CDI with one case of fulminant CDI. There was one recurrence within 90 days (9.1%). Patients were treated with PO vancomycin (72.7%) or IV metronidazole and PO vancomycin (27.3%), none were treated with metronidazole alone. None of the hospital strains were genetically related. There were two isolates with binary toxin gene (cdtB), one ribotype 027 (CD196) and one ribotype 078 (M120). Ninety-one percent of isolates had vanG-like gene cluster and vanZ1 originally identified in Enterococcus sp. erm(B), tet(M), and cfr(C) genes were also detected in several strains. All isolates were susceptible to vancomycin, metronidazole, and tigecycline. There was one strain with moxifloxacin resistance associated with the presence of erm(B) gene. None of the isolates were susceptible to clindamycin.

Conclusion
There were no widely circulating clones or direct transmissions found in this small sample of HO-CDI cases at our hospital. Like others have we demonstrate carriage of many vanG/Z genes without conferring phenotypic resistance to vancomycin. The origin and function of Van genes in C. difficile could be an area of future research.

Disclosures
All authors: No reported disclosures.
136. Factors Associated with Reduced Vancomycin Susceptibility in Pediatric Staphylococcus aureus Bacteremia
Authors: Ericson Jessica E , Curley Tara E , Canty Ethan A , Ansusinha Emily , Hamdy Rana F 
Published: October 2019

Abstract

Background
Vancomycin is often used empirically for treatment of pediatric Staphylococcus aureus bacteremia while susceptibility testing is being performed. Reduced vancomycin susceptibility (RVS) occurs when the minimum inhibitory concentration (MIC) for vancomycin is elevated, potentially resulting in decreased efficacy. Patient factors associated with RVS in pediatric S. aureus infections have not been well studied.

Methods
Children aged <18 years admitted from 2012 to 2016 to two tertiary care children’s hospitals with a blood culture positive for S. aureus were identified. Demographics, presence of comorbidities, hospitalizations in the year prior to the infection, surgical procedures in the 30 days prior to the infection, presence of a central venous catheter at diagnosis and methicillin-resistant (MRSA) vs. methicillin-susceptible S. aureus (MSSA) were abstracted from the electronic medical record using a structured data collection form. RVS was defined as a MIC >1 µg/mL as reported by the clinical microbiology laboratory. Wilcoxon rank-sum and Fisher’s exact test to compare continuous and categorical variables, respectively. A multivariable logistic regression model was used to evaluate the association of RVS with patient factors, MRSA vs. MSSA, admitting hospital, and year.

Results
We identified 221 S. aureus bloodstream infections. Most (84%) had RVS though there were differences by the hospital, 74% vs. 87%, P = 0.037. Bloodstream infections in the setting of a musculoskeletal infection were most common (36%), followed by central line-associated bloodstream infections (22%). The median age was similar between RVS and non-RVS infections, 3 (25th, 75th %tiles: 0, 9) vs. 5 (0, 12) but, when adjusted for patient factors, younger children were more likely to have RVS infections than older children, aOR: 0.92 (0.85, 0.99). Black children were more likely to have RVS than white children on both univariate and adjusted analyses (table).

Conclusion
RVS is common among pediatric S. aureus bloodstream infections and appears to be influenced by patient age and race but not by the source of the infection or other clinical factors.

Disclosures
All authors: No reported disclosures.
2433. Oral Vancomycin Plus Intravenous Metronidazole for Severe Clostridioides difficile Infection in Critically Ill Patients
Authors: Vega Ana D , Kristie Johnson J , Heil Emily , Blackman Alison L , Banoub Mary , Hopkins Teri , Leekha Surbhi , Claeys Kimberly C 
Published: October 2019

Abstract

Background
Molecular strain 027/NAP1/BI (NAP1) is a common cause of Clostridioides difficile infections (CDI). Despite high morbidity and mortality, optimal therapy remains elusive. There is also a paucity of data regarding optimal treatment of critically ill patients with severe CDI. We aimed to determine the impact of combination therapy (intravenous metronidazole [IV MTZ] plus oral vancomycin [PO VAN]) on clinical outcomes in critically ill patients with severe CDI, including those with NAP1 CDI.

Methods
Retrospective cohort of adult patients admitted to an intensive care unit (ICU) from April 2016 to October 2018 with a positive C. difficile PCR and an order for PO VAN. Patients with an order for IV MTZ for at least 72 hours formed the combination therapy group. A subset of patients had stool samples collected for NAP1 identification via GeneXpert C. difficile Epi molecular assay. The primary outcome was 30-day in-hospital mortality. A subgroup was matched using Acute Physiology and Chronic Health Evaluation (APACHE) II Scores. Cox regression was conducted to identify variables associated with time to mortality.

Results
138 patients were included; 60 (43.5%) received IV MTZ. Patients with IV MTZ had a higher median WBC count at diagnosis (20.9 vs 15.9, P = 0.0002) and were more likely to receive a higher dose of PO VAN (31.7% vs 12.9%, P = 0.008). 42 patients had NAP1 testing, 11 were positive (26.2%). There was no difference in probability of receiving IV MTZ based on APACHE II, however, NAP1+ were more likely to receive IV MTZ (50% vs 16.7%, P = 0.049). Clinical success was higher in the monotherapy group (46.8% vs 16.7%, P = 0.002). There was no difference in mortality (20% vs 14.1%, P = 0.368). In a subgroup of patients matched by APACHE II (n = 96), mortality remained non-significantly different (18.8% vs 14.6%, P = 0.785). Adjusted for IV MTZ, APACHE II (aHR = 1.06, 95% CI 1–1.12) and number of severity criteria (aHR = 2.08, 95% CI 1.40 – 2.97) were associated with mortality. There was no difference in mortality (9.1% vs 3.2% P = 0.459) or clinical success (18.2% vs 33.7%, P = 0.283) among NAP1+ vs. NAP- patients.

Conclusion
Our data questions the utility of IV MTZ with PO VAN for ICU patients with severe CDI, including NAP1 infections. There remains a possibility for confounding by indication in our analysis.

Disclosures
All authors: No reported disclosures.
2434. Proton Pump Inhibitor Use on Efficacy of Fecal Microbiota Transplant Administered by Trans-Oral Routes for Clostridioides Difficile Infection: A Systematic Review and Analysis
Authors: Hong Annie S , Yuan Yu Wen , Hong Jenny M , Azab Mohamed , Ohning Gordon V , Jayaraj Mahendran 
Published: October 2019

Abstract

Background
Current guidelines include fecal microbiota transplantation (FMT) in the management of recurrent Clostridioides difficile infections (CDI). However, FMT protocols are often facility dependent, and one variable is whether proton pump inhibitors (PPI) are given during preparation. Theoretically, PPIs reduce acidity and protects the transplanted microbiome for the most potent dose. On the other hand, PPIs have also been shown to negatively alter the microbiome and increase the risk of CDI. We conducted a systematic review of the literature to study PPI use on the efficacy of FMT delivered by the trans-oral route.

Methods
We searched PubMed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16th, 2018 using variations of keywords “fecal microbiota transplant” and “Clostridium difficile infection” with 4210 results. Two independent authors reviewed and excluded studies with unrelated topics, abstracts, case reports, or a low level of evidence. Studies with data on trans-oral FMT, PPI use, and the success rate were included. Final review yielded 11 studies including randomized controlled, case–control, cohort, retrospective and prospective trials. The primary outcome was the rate of FMT failure, defined as recurrence of symptoms with positive CDI testing at follow-up.

Results
Out of 233 included patients, 131 received a PPI per FMT protocol resulting in 27 cases of treatment failure. There were 23 cases of recurrence out of 102 patients who did not receive pre-FMT PPI. The primary outcome occurred in 20.6% in the group with PPI use vs. 22.6% in the group without (RR 0.91; CI 0.56 - 1.50). Limitations include the lack of studies directly comparing outcomes with respect to PPI use, and inability to control possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics.

Conclusion
We did not find a significant difference in efficacy between FMT protocols with regard to PPI use. It is possible that the theoretical benefit from increased survival of transplanted microbiota is offset by negative effects associated with PPIs. We suggest that routine use of PPIs in FMT be reconsidered in the absence of clear benefit. Further investigation is needed to optimize protocols for safety and efficacy.

Disclosures
All authors: No reported disclosures.
2435. The Impact of Treatment Strategy and Toxin Status on Outcomes of Patients with Clostridioides difficile Infections
Authors: Friedman Daniel , Zurek Karen , Asadi Leyla , Lee Mao-Cheng , Hoang Holly 
Published: October 2019

Abstract

Background
Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality and management continues to evolve. For laboratories that diagnose by detection of toxin gene, it is unclear whether reporting toxin production is additive to patient care. Furthermore, is there still a role for metronidazole (MNZ) given treatment guidelines now recommend vancomycin (VAN) as first-line therapy for non-severe cases? We analyzed cases of CDI in our hospital to assess outcomes of patients on MNZ vs. VAN and with or without toxin production.

Methods
A retrospective chart review of inpatients with CDI (based on detection of C. difficile toxin gene by PCR) was conducted between November 2017 and August 2018. Comparison of demographics and outcomes was performed in a) cases that were toxin-positive by enzyme immunoassay vs. negative and b) non-severe cases initially managed with MNZ vs. VAN.

Results
76 patients were included (46 toxin-positive, 30 toxin-negative). Toxin-positive patients were older (mean age 77 vs. 62, p = 0.002) but had similar disease severity and initial treatment. A CDI recurrence occurred in 22% vs 0% in the toxin-positive cases (p = 0.006). Any CDI-related complication occurred in 23% of toxin-negative and 35% of toxin-positive cases (ns). After adjusting for toxin-status, age, and severity, the odds ratio of the composite outcome of any complication with toxin-positive CDI was not significant (OR 1.45 95% CI 0.45 -4.6, p = 0.52).
There were 37 (49%) patients with non-severe CDI (27 MNZ, 10 VAN). Patients treated with VAN had higher stooling/day (6.3 vs 4.4, p = 0.04) and heart rate (p = 0.02). Initial MNZ use was associated with treatment escalation in 48% of cases compared with 10% in those treated with VAN alone (p = 0.03). CDI-associated mortality was higher in the VAN group (2/10 vs 0/27, p = 0.017). The rate of other complications was not significantly different.

Conclusion
Although no difference in the composite outcome of any CDI-related complication was detected between toxin positive vs negative patients, toxin-positivity may predict patients at risk for subsequent recurrence. Patients with non-severe CDI did not have increased risk of complications when managed with MNZ; however, they were more likely to require treatment escalation.

Disclosures
All authors: No reported disclosures.
2437. First-line Fidaxomicin Use in High-risk Inpatients Reduces Recurrence Rates
Authors: Kohinke Rose , McDaniel Lauren , Perhac Angela , Everson Nathan 
Published: October 2019

Abstract

Background
Fidaxomicin is recommended by the 2018 Infectious Diseases Society of America (IDSA) guidelines as a first-line treatment in adult patients with uncomplicated Clostridioides difficile infection (CDI). Carilion Roanoke Memorial Hospital (CRMH) implemented a clinical decision order set directing providers to initiate fidaxomicin for CDI in patients at high risk of recurrence. The purpose of this study was to assess the impact of fidaxomicin on patient outcomes.

Methods
This quasi-experimental study included adults with a first episode or first recurrence of CDI before and after order set implementation. Patients receiving laxatives within 24 hours of testing and those with fulminant CDI were excluded. Pre-implementation was defined as May 2017 to November 2017 and post-implementation as May 2018 to November 2018. The primary endpoint was recurrence (diarrhea and a positive GDH with toxin or PCR within 30 days post-treatment). Secondary endpoints were clinical cure (resolution of symptoms within 2 days of completing therapy), global cure (cure with no recurrence at 3 months), mortality, and readmissions. Partial courses of fidaxomicin (i.e., patients discharged on another agent) were also evaluated.

Results
A total of 282 patients were included. In the pre-group, 59.1% received metronidazole, 39.6% oral vancomycin, and 1.3% fidaxomicin. In the post-group, fidaxomicin use increased to 52.3% and oral vancomycin was 44.5%. There was a significant improvement in recurrence (30.2% vs 17.1%, P = 0.019). Global cure and CDI upon readmission also improved in the post-group (Table 1). In patients receiving partial courses of fidaxomicin, recurrence (9.3% vs 25%, P = 0.19), global cure (86% vs 75%, P = 0.44), and infection on readmission (28.6% vs 37.5%, P = 0.67) were similar.

Conclusion
Fidaxomicin as a first-line agent in high-risk CDI patients decreased recurrence and increased global cure.

Disclosures
All authors: No reported disclosures.
2448. Clinical Presentation and Outcomes of Long-Term Care Residents with Coronavirus Respiratory Infection: A Retrospective Cohort Study
Authors: Williams Victoria R , Pajak Dariusz , Salt Natasha , Leis Jerome A 
Published: October 2019

Abstract

Background
Human coronaviruses (CoVs) are a major cause of respiratory infection and institutional outbreaks, yet the epidemiology and clinical outcomes of these viruses is poorly described among the elderly residing in long-term care facilities (LTCFs).

Methods
We performed a retrospective cohort study of LTCF residents with positive nasopharyngeal or mid-turbinate swabs for CoVs (OC43, 229E, NL63 and HKU1) between January 2013 and December 2018. Demographic and clinical data were obtained from resident charts including clinical presentation, treatment, outcome, and transmission to other residents. Variables were compared using univariate analysis.

Results
3268 residents met inclusion criteria (median age 93 years, 90% male) comprising 7.5% (246/3268) of all positive respiratory virus specimens detected during the study period. 97(39%) of cases were associated with a respiratory outbreak while 149(61%) were sporadic cases that did not result in transmission. OC43 (52%) was the most commonly identified CoV and was more commonly associated with outbreak cases (76% vs. 37%; P < 0.001). In total, 87% of all cases had two or more of runny nose/congestion, cough, sore throat/hoarse voice or fever. The most common symptoms among residents were cough (85%), runny nose/congestion (79%), and sore throat/hoarse voice (59%) and only 17% of residents had a measured temperature of ≥ 37.8C. Only 6% of residents received antibiotic treatment for suspected secondary bacterial pneumonia. The 30-day mortality rate was 3.7% with 67% of deaths attributable to the CoV infection. There was no statistically significant difference in symptoms, treatment or outcomes associated with outbreaks or seasonality.

Conclusion
CoVs make up an important proportion of respiratory viral infections among LTCF residents and may result in frequent outbreaks. Most residents remain afebrile and have self-limited illness while only a small minority develop secondary bacterial pneumonia and death. Given these findings the benefits of control measures should be weighed against the impact on resident quality of life.

Disclosures
All authors: No reported disclosures.
2460. Hospital-Wide Outbreak of Serratia marcescens of Unclear Source: When Extensive Infection Control Measures Are Needed
Authors: Tayyar Ralph , Weyhmuller Carol , Fasano Caitlin , Aridi Jad , Sherman Eileen , Ingerman Mark , Gilbert Brett 
Published: October 2019

Abstract

Background
Nosocomial outbreaks of Serratia marcescens have been widely reported and the source is identified in most cases. We report a Serratia marcescens outbreak in a community hospital with no obvious source.

Methods
An epidemiologic investigation was started after an outbreak was suspected. Clinical data were collected from charts of patients with positive culture for Serratia marcescens. Molecular relatedness of available isolates was determined by pulsed-field gel electrophoresis.

Results
Between December 2016 and August 2017, 13 non-pigmented Serratia marcescens isolates were identified from 11 patients. Bacteria were isolated from blood, abdominal and respiratory cultures. Susceptibility profiles showed variable resistance to ceftriaxone, ceftazidime, imipenem, tobramycin and aztreonam. Infection control measures: Isolates were identified from adult patients who underwent various cardiothoracic/vascular surgeries. Patients were traced back to a single floor of the new hospital building. To control this outbreak, the infection prevention team started with hand hygiene initiatives and observations, environmental sampling, and reviewing management of ventilator, dialysis equipment, and ECMO machines. Ice machine carbonless filters were installed, UV disinfection systems were used, and new TEE cleaning rooms were designated. In conjunction with recommendations of department of health, hospital was contracted with a water cleaning company; laminar flow aerators were installed, water sampling plan was implemented and ultimately the whole building’s water system was hyper-chlorinated.

Conclusion
While water contamination was the most likely source, a specific cause could not be identified. An important lesson learnt is the quick implementation of infection control measures after identifying infected patients is key in controlling an outbreak.

Disclosures
All authors: No reported disclosures.