Treatment Of C. Difficile Infection Research Articles

Impact of a division-wide bundle on hospital-acquired Clostridioides difficile cases, antibiotic days of therapy, testing appropriateness, and associated financial costs.

ABSTRACTIntroduction:Updated international guidelines recommend the use of a two-step algorithm (glutamate dehydrogenase [GDH] or nucleic-acid amplification test [NAAT] plus toxin) rather than NAAT alone for the diagnosis of Clostridioides difficile (formerly Clostridium difficile) infections. The goal of our project was to evaluate the impact of a new bundle on the rate of hospital-acquired C. difficile infections (CDIs), hospital-acquired CDI standardized infection ratio (SIR), antibiotic days of therapy (DOT), and financial cost.Materials and Methods:The new bundle was implemented in April 2018. This bundle was implemented across five hospitals in Catholic Health Initiatives (CHI) Texas Division. The bundle included a switch from NAAT to a two-step process (GDH and toxin). We placed the new test in an order panel which included enteric isolation and required indications for C. difficile testing. We used quarterly data pre- and post-intervention to calculate SIR and DOT.Results:In the pre-intervention period, 15.5% of the total 3513 C. difficile NAAT was positive. In the post-intervention period, 5.7% of a total of 2845 GDH and toxin assays was positive for both GDH and toxin (P < 0.0001). SIR, which adjusts for denominator and change in testing methodology, also dropped from 1.02 to 0.43. The estimated cost associated with positive C. difficile cases dropped from 1,932,150 USD to 1,113,800 USD with an estimated yearly cost saving of 794,150 USD. Compliance with enteric isolation improved from 73.1% to 92.5% (P = 0.008).Conclusion:The new testing bundle led to a marked reduction in hospital-acquired CDI and unnecessary treatment, reduction in C. difficile testing, an increase in compliance with enteric isolation, and significant cost savings.

729. Real World Efficacy of Bezlotoxumab for Prevention of Clostridioides Difficile Recurrence in Immunosuppressed Patients

BackgroundBezlotoxumab has been shown to prevent recurrent episodes of C. difficile infection (CDI) in high risk patients. Current studies define therapeutic efficacy within the first 12 weeks when the risk of recurrence is greatest. However, the risk of recurrent CDI can occur beyond the 12-week window in the immunosuppressed population. Given that bezlotoxumab has detectable serum levels for up to 24 weeks after infusion, the primary endpoint is to determine overall efficacy in immunosuppressed patients with recurrent CDI at 4 weeks, 12 weeks, and 24 weeks after initial infusion. Secondary endpoints consist of risk factors for recurrent CDI, treatment of CDI, and antibiotics usage before and after bezlotoxumab.MethodsThis analysis included immunosuppressed patients at high risk for CDI recurrence who received bezlotoxumab from February 2017 to December 2019. Patients were excluded if they were not immunosuppressed, had no follow-up appointments, and/or without a C. difficile positive test. High risk antibiotics included fluoroquinolones, beta lactamase inhibitors, third generation cephalosporins, or carbapenems.ResultsTwenty-seven bezlotoxumab doses were given to 26 patients. Baseline characteristics for CDIs prior to bezlotoxumab is reported in Table 1. The overall CDI recurrence rate at all intervals after bezolotoxumab was 4 (15%), one recurrent CDIs occurred at < 4 weeks, two recurrent CDIs occurred at 5-12 weeks, and one recurrent CDI at 13-24 weeks. High risk antibiotics were given in 2/4 (50%) of CDIs recurrences and 22/75 (29%) in the non-recurrence group. Of the four CDI recurrences, all were mild to moderate in disease severity given no evidence of colitis was seen on CT scan and a median Zar score of 1 (range 0-1) due to age > 60 years.Table 1: Baseline Characteristics ConclusionIn immunosuppressed patients with CDI, bezlotoxumab is effective at reducing CDI episodes up to 24 weeks. Additionally, this highly antibiotic exposed population continued to receive benefit up to 24 weeks after bezlotoxumab.Disclosures All Authors: No reported disclosures

792. Evaluation of Persistent Diarrhea and Recurrence Following Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection

BackgroundPatients treated for C. difficile infection (CDI) have high rates of recurrence. Fecal microbiota transplantation (FMT) is an effective therapy for patients with recurrent CDI. While highly successful, there are limited data to help clinicians predict which patients are more likely to have adverse outcomes following FMT. Here we aim to identify factors that are associated with recurrent CDI or persistent diarrhea following FMT for treatment of recurrent CDI.MethodsAt a large academic medical center, we conducted a retrospective cohort study of patients receiving their first FMT for recurrent CDI using product from a commercial stool bank. Patients were included if follow-up data on post-FMT outcomes were available. Through manual chart review, we collected information on patient demographics, comorbid disease burden, prior CDI, and antibiotic use prior to FMT. Outcomes included recurrent CDI and persistent diarrhea not from CDI, both within 90 days of FMT. Unadjusted and adjusted analyses via logistic regression were used to model the outcomes.ResultsThis study included 81 subjects, of which 72 (89%) experienced no recurrence following FMT. In the multivariable model, the odds of recurrence decreased as BMI rose and with each 1-log increase in the duration of antibiotic therapy for CDI prior to FMT (Table). Among the 72 subjects not diagnosed with recurrent CDI following FMT, 26 (36%) experienced persistent diarrhea for which further work-up or therapy was recommended. History of irritable bowel syndrome (IBS) was the only predictor independently associated with persistent diarrhea while adjusting for age and number of prior CDI episodes (Table). IBS was also the most common etiology identified by the subjects’ clinical teams for persistent diarrhea following FMT.Table. Multivariable models of adverse outcomes following FMT for CDI ConclusionWe found FMT for CDI at our center to be effective in curing CDI without subsequent recurrence, at a level similar to what is seen from randomized controlled trials. Higher BMI and longer duration of antibiotic therapy for CDI prior to FMT may be protective against recurrence. Still, a significant proportion of patients experienced persistent non-C. difficile related diarrhea, and patients with a history of IBS were more likely to have persistent diarrhea after FMT.DisclosuresKrishna Rao, MD, MS, Bio-K+ International, Inc. (Consultant)Merck and Co., Inc. (Research Grant or Support)Roche Molecular Systems, Inc. (Consultant)

247. Validation of the Use of Oral Vancomycin Following Positive Admission Screening Testing for C. difficile

Background Clostridioides difficile can cause a severe infectious colitis and is often associated with significant morbidity and mortality. C. difficile infection (CDI) is defined as the presence of diarrhea plus a positive stool test, whereas C. difficile colonization is defined as a positive stool test in the absence of diarrhea or the presence of diarrhea attributable to causes other than CDI. Widespread use of stool polymerase chain reaction (PCR) testing, especially within the first 3 days of admission, has become common at our institution and has been associated with increased number of positive C. difficile tests results. However, C. difficile colonization rates may be 15% or higher. Oral (PO) vancomycin (vanc) is first line therapy for the treatment of CDI. We sought to evaluate the appropriateness of use of PO vanc in patients who tested positive for C. difficile via stool PCR within 3 days of admission.MethodsWe reviewed the clinical history, presence of diarrhea, risk factors for diarrhea, treatment and use of an infectious disease (ID) consultation for all patients 18 years of age or older found to test positive for C. difficile by PCR on stool assays during the first 3 days of admission from 07/01/18 to 12/31/18.ResultsA total of 228 patients met inclusion criteria. 183 (80%) received PO vanc while 45 (20%) did not. 131 (71.6%) of patients who received PO vanc had diarrhea, 39 (21.3%) did not have diarrhea, 13 (7.1%) the presence of diarrhea was unknown. 41 of 143 (28.7%) of patients without ID consults received PO vanc despite not having diarrhea, while 11 of 40 (27.5%) patients seen by ID received PO vanc despite not having diarrhea (p=0.888).ConclusionMost patients who tested positive for C. difficile received PO vanc had documented diarrhea, meeting the definition of CDI. However, over 1 in 5 (21.3%) of patients who received PO vanc did not have diarrhea and may have been colonized rather than have true CDI. ID consultation did not decrease the number of patients without diarrhea who received PO vanc or prevent treatment of colonized patients. This work reveals there may be an opportunity for improvement regarding management of CDI vs. C. difficile colonization which may enhance antibiotic stewardship and the appropriate use of PO vanc.Disclosures All Authors: No reported disclosures

Navigating changes in Clostridioides difficile prevention and treatment.

Clostridioides difficile (C. difficile, previously known as Clostridium difficile) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments. DISCLOSURES: Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.

Development and verification of an enzyme-linked immunosorbent assay for the quantification of toxoid A and toxoid B from Clostridioides difficile

Clostridioides difficile (C. difficile) is the most common cause of nosocomial antibiotic associated diarrhoea. The incidence of C. difficile infection (CDI) has been rising worldwide over the last 20 years with consequent rises in morbidity, mortality and healthcare costs, although the incidence has fallen in the UK over the last few years. Confirmation of diagnosis and early intervention are critical to the management of CDI. The standard treatment for CDI is the administration of antibiotics. However, vaccination has been recognized as the most cost-effective treatment for the prevention and possible long-term protection against CDI episode. There are several promising vaccine candidates in various stages of development. Many of these vaccines have displayed good efficacy for CDI under laboratory conditions or in clinical trials. With the emergence of vaccines against C. difficile, here we describe the development and verification of an Enzyme Linked Immunosorbent Assay (ELISA) that can be used for the quality control testing of candidate vaccines against C. difficile through the measurement of vaccine antigen content. Verification of the assay was performed by assessment of specificity, sensitivity, intermediate precision and relative accuracy. The ELISAs were specific for the toxoids being detected and the detection limit of the assay for toxoid A was 4.88 ng/mL and 3.91 ng/mL for toxoid B. The geometric coefficients of variation for intermediate precision did not exceed 25% and relative accuracy was within 77–130%. We therefore conclude that the ELISA described here is sufficiently sensitive, specific, precise and accurate for use for the quality control testing of candidate C. difficile vaccines.

Faecal Microbiota Transplantation is Effective for the Initial Treatment of Clostridium difficile Infection: A Retrospective Clinical Review.

IntroductionClostridium difficile (C. difficile) infection (CDI) is commonly recognised as a nosocomial infection but is increasingly identified in patients in the community. Antimicrobial exposure which compromises gut microbiota is the main risk factor for CDI, although antibiotics remain the main treatment for this infection. Faecal microbiota transplantation (FMT) is also an effective treatment for CDI. FMT involves the transfer of microbiota from a healthy donor to an unwell patient. Currently FMT is mostly used after repeated antibiotic treatments fail to cure CDI. This study investigated the effect of FMT as first-line treatment for CDI to avoid repeated antibiotic damage of the microbiome.MethodsThis retrospective, single-centre study included 59 patients between 2012 and 2017 whose first episode of CDI was treated with FMT. The patients’ symptoms and presence of C. difficile in stool samples both at the baseline and post treatment were documented.ResultsFifty-four patients completed a final stool test 4–8 weeks post treatment in which 98% of patients were negative for C. difficile. There were no adverse effects. There was a significant reduction in abdominal pain, diarrhoea, bloating and blood in the stool at 4–8 weeks post treatment. Data from 24 patients who completed an extended 6 months follow-up showed significant reduction in abdominal pain, diarrhoea and blood in the stool.ConclusionThis study demonstrates the safety and efficacy of FMT as first-line treatment for patients’ initial episode of CDI. Future randomised studies are required to confirm FMT as the initial treatment for CDI.

Treatment issues in recurrent Clostridioides difficile infections and the possible role of germinants.

Clostridioides difficile is the number one cause of hospital-acquired infections in the United States and one of the CDC's urgent-level pathogen threats. The inflammation caused by pathogenic C. difficile results in diarrhea and pseudomembranous colitis. Patients who undergo clinically successful treatment for this disease commonly experience recurrent infections. Current treatment options can eradicate the vegetative cell form of the bacteria but do not impact the spore form, which is impervious to antibiotics and resists conventional environmental cleaning procedures. Antibiotics used in treating C. difficile infections (CDI) often do not eradicate the pathogen and can prevent regeneration of the microbiome, leaving them vulnerable to recurrent CDI and future infections upon subsequent non-CDI-directed antibiotic therapy. Addressing the management of C. difficile spores in the gastrointestinal (GI) tract is important to make further progress in CDI treatment. Currently, no treatment options focus on reducing GI spores throughout CDI antibiotic therapy. This review focuses on colonization of the GI tract, current treatment options and potential treatment directions emphasizing germinant with antibiotic combinations to prevent recurrent disease.

Fecal Microbiota Transplantation in Recurrent Clostridium Difficile Infection: Is it Superior to Other Conventional Methods?

Clostridium difficile (C. difficile) is a gram-positive species of spore-forming bacteria. C. difficile infection (CDI) is one of the most common hospital-acquired infections in the United States, mainly caused by the use of recent antibiotics that leads to intestinal dysbiosis. Recurrent C. difficile infection (rCDI) often occurs after the successful treatment of CDI. Approximately, 30% of patients experience a clinical recurrence of prior symptoms within eight weeks of antibiotic cessation. This present literature review covers the current pathophysiology of CDI, risk factors for infection, diagnostic methods, several treatment modalities, and the potential use of fecal microbial transplant (FMT) for patients with multiple recurrent CDIs. Recent studies have focused on FMT, with an efficacy rate of nearly 90% in multiple recurrent CDI settings. Despite its efficacy, it is not commonly used as first-line treatment. More studies are needed to establish this therapy as the first option in patients with rCDI.

Clinical impact of a Clostridioides (Clostridium) difficile bedside infectious disease stewardship intervention.

ObjectivesTo evaluate the clinical impact of a bedside visit to patients with a positive Clostridioides difficile test on the antimicrobial stewardship of C. difficile infection (CDI) and non-C. difficile infections.MethodsAll patients ≥18 years old with positive CDI laboratory tests hospitalized between January 2017 and August 2017 received an immediate bedside intervention that consisted mainly of checking protective measures and providing recommendations on infection control and the management of CDI and other infections.ResultsA total of 214 patients were evaluated. The infectious disease (ID) physician was the first to establish protective measures in 25.2% of the cases. In 22/29 (75.9%) cases, physicians in charge accepted ID consultant recommendations to stop CDI treatment in asymptomatic patients. Unnecessary non-CDI antibiotics were discontinued in 19.1% of the cases. ID recommendations were not accepted by physicians in charge in only 12.6% of the cases.ConclusionsA bedside rapid intervention for patients with a CDI-positive faecal sample was effective in avoiding overdiagnosis and unnecessary antibiotic treatment, optimizing anti-CDI drugs, increasing compliance with infection control measures and providing educational advice.

Utilization of a Clostridioides Difficile Testing Algorithm to Promote Evidence-based Laboratory Testing

<h3>Background</h3> Clostridioides difficile is a spore forming bacteria shed in feces. Clinical symptoms of C. difficile infection (CDI) include diarrhea, fever, loss of appetite, nausea and abdominal pain. It accounts for 15-25% of all episodes of antibiotic associated diarrhea. The Centers for Disease Control and Prevention (CDC) reported that in 2017 there was an estimated quarter million CDI cases and 12,800 associated deaths in hospitalized patients. C.difficile colonization is more common than CDI. Colonized patients may test positive for C.difficile organism or its toxin but do not display clinical signs and symptoms. C. difficile impacts quality of care, length of stay, reimbursement, antibiotic utilization and patient satisfaction <h3>Methods</h3> A multidisciplinary group assembled in 2017 with the goal of decreasing CDI. Team members reviewed past CDI cases and surveyed clinical staff regarding CDI identification and infection control procedures. Based on this information, establishing evidence-based testing criteria was identified as an opportunity. A CDI testing algorithm was developed based on published clinical practice guidelines. This algorithm was implemented as a paper checklist, completed by nursing staff. In July 2019, the algorithm was fully integrated into the electronic medical record (EMR) as automated ordering rules. <h3>Results</h3> The number of C.difficile tests ordered was reduced by 39% with an associated cost reduction of $36,988. There was a CDI case reduction of 22% post implementation. <h3>Conclusions</h3> Implementation of an evidence-based C.difficile testing algorithm was associated with a decrease in tests ordered and associated costs. The greatest reduction occurred after the algorithm was integrated into the EMR ordering system. Following evidence-based testing guidelines is important in ensuring accurate identification and guiding appropriate treatment of CDI. A C.difficile testing algorithm is an important piece of a multifaceted strategy, which can contribute to a decrease in CDI rates.

Optimal vancomycin dose in the treatment of Clostridium difficile infection, antimicrobial stewardship initiative

C. difficile infections (CDI) are increasingly recognized as a leading cause of infectious diarrhea, with increasing morbidity and mortality. Treatment primarily centers around oral vancomycin treatment. A wide range of dosing regimens exist in clinical practice, with little evidence to help distinguish the therapeutic benefit between them. This is a retrospective cohort study conducted at an academic medical center that enrolled adult patients admitted with CDI. The primary outcome was a composite of complete or partial cure at the end of treatment and was assessed using a test of equivalency with a 20% equivalency limit. Subjects were divided into low dose (125 mg) or high dose (250 mg or 500 mg) of oral vancomycin dosed every 6 hours. Overall, 78 patients were included who received low dose vancomycin and 33 who received high dose. Generally, the two groups were similar, except the low dose group had significantly more leukocytosis and less ICU admission or hypotension compared to the high dose group. Equivalency between the two treatment groups was demonstrated (Absolute Risk Difference −0.022, 90% confidence interval: −0.13 to 0.18, p = 0.03). A stepwise logistic regression identified gender, baseline albumin, and ICU admission as significant predictors of the chance for complete or partial cure. No differences between groups for the secondary outcomes of 90-day readmission/recurrence, 30-day all-cause mortality, or time to resolution of diarrhea were demonstrated. Low dose oral vancomycin was demonstrated to result in equivalent outcomes compared to high dose vancomycin for the treatment of CDI.

Rapid in Vitro Assessment of Clostridioides difficile Inhibition by Probiotics Using Dielectrophoresis to Quantify Cell Structure Alterations.

Clostridioides difficile (C. difficile) infection (CDI) is the primary cause of nosocomial antibiotic-associated diarrhea, with high recurrence rates following initial antibiotic treatment regimens. Restoration of the host gut microbiome through probiotic therapy is under investigation to reduce recurrence. Current in vitro methods to assess C. difficile deactivation by probiotic microorganisms are based on C. difficile growth inhibition, but the cumbersome and time-consuming nature of the assay limits the number of assessed permutations. Phenotypic alterations to the C. difficile cellular structure upon interaction with probiotics can potentially enable rapid assessment of the inhibition without the need for extended culture. Because supernatants from cultures of commensal microbiota reflect the complex metabolite milieu that deactivates C. difficile, we explore coculture of C. difficile with an optimal dose of supernatants from probiotic culture to speed growth inhibition assays and enable correlation with alterations to its prolate ellipsoidal structure. Based on sensitivity of electrical polarizability to C. difficile cell shape and subcellular structure, we show that the inhibitory effect of Lactobacillus spp. supernatants on C. difficile can be determined based on the positive dielectrophoresis level within just 1 h of culture using a highly toxigenic strain and a clinical isolate, whereas optical and growth inhibition measurements require far greater culture time. We envision application of this in vitro coculture model, in conjunction with dielectrophoresis, to rapidly screen for potential probiotic combinations for the treatment of recurrent CDI.

In Vivo Targeting of Clostridioides difficile Using Phage-Delivered CRISPR-Cas3 Antimicrobials.

Clostridioides difficile is an important nosocomial pathogen that causes approximately 500,000 cases of C. difficile infection (CDI) and 29,000 deaths annually in the United States. Antibiotic use is a major risk factor for CDI because broad-spectrum antimicrobials disrupt the indigenous gut microbiota, decreasing colonization resistance against C. difficile Vancomycin is the standard of care for the treatment of CDI, likely contributing to the high recurrence rates due to the continued disruption of the gut microbiota. Thus, there is an urgent need for the development of novel therapeutics that can prevent and treat CDI and precisely target the pathogen without disrupting the gut microbiota. Here, we show that the endogenous type I-B CRISPR-Cas system in C. difficile can be repurposed as an antimicrobial agent by the expression of a self-targeting CRISPR that redirects endogenous CRISPR-Cas3 activity against the bacterial chromosome. We demonstrate that a recombinant bacteriophage expressing bacterial genome-targeting CRISPR RNAs is significantly more effective than its wild-type parent bacteriophage at killing C. difficile both in vitro and in a mouse model of CDI. We also report that conversion of the phage from temperate to obligately lytic is feasible and contributes to the therapeutic suitability of intrinsic C. difficile phages, despite the specific challenges encountered in the disease phenotypes of phage-treated animals. Our findings suggest that phage-delivered programmable CRISPR therapeutics have the potential to leverage the specificity and apparent safety of phage therapies and improve their potency and reliability for eradicating specific bacterial species within complex communities, offering a novel mechanism to treat pathogenic and/or multidrug-resistant organisms.IMPORTANCEClostridioides difficile is a bacterial pathogen responsible for significant morbidity and mortality across the globe. Current therapies based on broad-spectrum antibiotics have some clinical success, but approximately 30% of patients have relapses, presumably due to the continued perturbation to the gut microbiota. Here, we show that phages can be engineered with type I CRISPR-Cas systems and modified to reduce lysogeny and to enable the specific and efficient targeting and killing of C. difficilein vitro and in vivo. Additional genetic engineering to disrupt phage modulation of toxin expression by lysogeny or other mechanisms would be required to advance a CRISPR-enhanced phage antimicrobial for C. difficile toward clinical application. These findings provide evidence into how phage can be combined with CRISPR-based targeting to develop novel therapies and modulate microbiomes associated with health and disease.

Clinical impact of a pharmacist-led antimicrobial stewardship initiative evaluating patients with Clostridioides difficile colitis

Clostridioides difficile is the most common cause of healthcare-associated infection and gastroenteritis-associated death in the USA. Adherence to guideline recommendations for treatment of severe C. difficile infection (CDI) is associated...

Clostridium Difficile Infection Among Hematopoietic Stem Cell Transplant Recipients and Subsequent Development of Graft-Versus-Host Disease

Introduction: Clostridium difficile (C. difficile) is an anaerobic gram positive rod that colonizes 20-40 % of hospitalized patients and the most common cause of antibiotic-associated diarrhea. The clinical manifestations of C. difficile infection (CDI) range from asymptomatic carriage to severe fulminant infection, leading to bowel perforation and death. Stem cell transplantation (SCT) recipients are at risk of CDI due to prolonged neutropenia, use of broad-spectrum antibiotics, mucosal damage and changes in intestinal microbiota induced by cytotoxic chemotherapy, microbial co-infection and possibly graft-versus-host disease (GVHD). The incidence of CDI amongst patients undergoing autologous SCT varies between five and 15 % and among those undergoing allogenic SCT 12 and 34% in literature1-5. Some studies have found a strong association between CDI and GVHD, gut GVHD and/or severe GVHD1-4 but this was not universally demonstrated5. Many studies looking at CDI in the SCT setting are limited by the ubiquity of traditional risk factors for CDI and small sample sizes. Methods: In this retrospective observational study, we aimed to review the epidemiology and clinical management of CDI in our autologous and allogeneic SCT recipients and subsequent clinical outcomes including development of GVHD. All recipients of autologous and allogeneic SCT at Vancouver General Hospital over the 10-year period between January 1, 2008 and December 31, 2017, who had diarrhoea and at least one positive stool test for C. difficile toxin by polymerase chain reaction were eligible for inclusion. Patient demographics, transplant details including GVHD prophylaxis, treatment for CDI, complications from CDI and subsequent development of acute and chronic GVHD and survival outcomes were collected by means of review of their electronic and written clinical records. An ethics approval was obtained from the hospital ethics committee. Results: Out of the 2104 patients who underwent SCT during the study period, 277 (13.2%) had at least one episode of C. difficile positive diarrhea. The incidence was higher among recipients of allogeneic SCT (19.6%) compared to autologous SCT recipients (9.6%). The majority of the patients (86.7%) were treated with oral metronidazole as a first line therapy and 18.9% required a second line treatment, with oral vancomycin in most cases, due to persistent symptoms with toxin positivity. 21% had recurrence of CDI after an initial successful treatment and 9.4% had two or more recurrences. There was no death directly attributable to acute CDI and the rate of major complications was low. Two patients required an intensive care unit admission with fulminant CDI and one patient underwent bowel resection. 57% of allogeneic SCT patients with post-transplant CDI subsequently developed acute GVHD (45.8% grade 2 or higher acute GVHD, 34% gut GVHD). 60.6% developed chronic GVHD (46.9% moderate to severe GVHD, 19.2% gut chronic GVHD). The median progression free survival was 670.5 days (range 1-3938) and the overall survival time was 984.5 days (range 10-3938). The commonest cause of death was malignancy relapse. Conclusion: The incidence of CDI among autologous and allogeneic SCT recipients in British Columbia was 9.6% and 19.6% respectively. There was no death immediately attributable to CDI and few patients developed fulminant CDI. Of the SCT patients who had CDI, 57% and 60.6% subsequently developed acute and chronic GVHD respectively.

779. Impact of updated IDSA practice guidelines on the treatment of Clostridium difficile infections in the United States

BackgroundIDSA published updated practice guidelines for C. difficile infections (CDI) in February 2018. Since publication of previous CDI guidelines in2010, randomized clinical trials (RCTs) have demonstrated benefit of oral (po) vancomycin or fidaxomicin over metronidazole in at least some types of CDI. Updated guidelines endorsed vancomycin or fidaxomicin as recommended treatment for initial and recurrent nonfulminant CDI episodes, and vancomycin as treatment for fulminant CDI. We studied the use of po vancomycin, fidaxomicin and metronidazole in the United States before and after publication of updated guidelines.MethodsWe obtained US antibiotic prescription data (IQVIA, Durham, NC) since 2013, and used standard dosing regimens for treatment of initial CDI to estimate numbers of infections treated with different agents. Po vancomycin and fidaxomicin are used exclusively against known or suspected CDI. Metronidazole is used to treat CDI and other infections. IQVIA data do not capture indications for prescriptions.ResultsTreatment courses of po vancomycin and fidaxomicin increased by 45% (n = 126,729 increase) and 44% (n = 11,243 increase), respectively, over the 12 months after publication of the updated CDI guidelines compared with 12 months before publication (Figure, second arrow; Table). Increased use of both agents was evident in the first month after guidelines were published. Over the same 12 month periods, treatment courses of po metronidazole decreased by 3% (190,430 decrease). In comparison, treatment courses of po vancomycin increased by 24% (n = 47,219 increase) over the 12 months after publication of the multi-national PACT study in August 2014 (Figure, first arrow), which demonstrated superiority of vancomycin over metronidazole. Since 2013, there were no significant increases in the use of fidaxomicin until publication of the updated guidelines.ConclusionUpdated IDSA guidelines have had a major impact on treatment of CDI in the US. RCT data used for guideline updates have been available since 2007–14 and 2011–12 for po vancomycin and fidaxomicin, respectively. IDSA should provide more timely updates to practice guidelines as new data emerge. Annual or bi-annual updates posted in electronic or other nontraditional formats may be more efficient than publishing long-form articles. Disclosures All authors: No reported disclosures.

2363. Implementation of a Multi-Step Diagnostic Algorithm for C. difficile Infection

BackgroundThe diagnosis of C. difficile infection (CDI) in the hospital is challenging asymptomatic colonization rates vary between 3% and 26%. Guidelines recommend multistep testing for CDI diagnosis. On July 1, 2018 a two-step testing algorithm was implemented at our institution. Positive nucleic acid amplification test (NAAT) results reflexed to a toxin enzyme immunoassay (EIA) test. The EIA test result was then used for NHSN reporting; however, both test results were visible to the clinician. Updated guidance on the interpretation of the test and treatment of CDI was released to the medical staff in July. We compared the incidence of CDI lab ID events per 1000 patient-days and the rate of C. difficile antibiotic starts before and after the implementation of the testing algorithm.MethodsA retrospective observational study was performed at an 800 bed regional medical center. CDI lab ID events between January 1 and December 31, 2018 were reviewed. Antibiotic initiation of intravenous (IV) and oral (PO) metronidazole and PO vancomycin was collected for all hospitalized patients diagnosed with C. difficile. The incidence of hospital onset (HO) and community-onset (CO) lab ID events as well as the rate of antibiotic starts were compared before and after implementation of the algorithm using a two-sided z test for proportions with an alpha of 0.05.ResultsThe incidence of HO and CO lab ID events per 1000 patient-days decreased significantly from 0.56 to 0.16 (P < 0.0001) and 1.18 to 0.3 (P < 0.0001) after implementation of the testing algorithm (Figure 1). The CDI SIR decreased from 0.729 to 0.322, (P = 0.0048). The rate of antibiotic starts per 1,000 patient-days for IV and PO Metronidazole decreased significantly from 1.1 to 0.45 (P < 0.0001) and 0.86 to 0.35 (P < 0.0001), respectively. PO Vancomycinstarts decreased from 1.51 to 1.23 (P = 0.11) (Table 1).ConclusionA two-step algorithm for diagnosing CDI decreases the overall number of HO and CO C. difficile lab ID events and decreases overall antimicrobial use for CDI. Disclosures All authors: No reported disclosures.

2578. Narrow-Spectrum Antibiotic Treatment of Clostridium difficile Infection Improves Preservation of Intestinal Metabolic Profile

BackgroundCommensal gut bacteria are thought to protect against C. difficile infection (CDI) by producing metabolites that inhibit C. difficile germination and growth. Alternatively, the protective effect could reflect nutrient competition or other mechanisms of chemical communication that also involve the host. CDI treatment using a broad-spectrum antibiotic such as vancomycin (VAN) dramatically depletes commensal bacteria. This dysbiosis can persist for several weeks after end-of-therapy (EOT), and is associated with increased recurrence risk. In this study, we investigate the hypothesis that treating CDI with a more selective antibiotic reduces collateral damage to the intestinal microbiota, preserving or restoring a CDI-inhibitory metabolic profile.MethodsStool samples were collected from CDI patients treated with either a narrow- (RDZ) or broad-spectrum antibiotic (VAN) at days 1, 10 (EOT), 25, and 40. Global metabolite profiles were measured by untargeted LC-MS.ResultsUntargeted metabolite analysis showed broad differences in the metabolic activity of intestinal microbiota of RDZ- and VAN-treated subjects (Figure 1). At EOT, 28% of LC-MS features detected in both RDZ and VAN samples were differentially present (FDR corrected P-value <0.05). Over 80% of the differentially present features were elevated in the RDZ group, indicating diminished capacity of microbiota from VAN subjects to generate diverse metabolic products. Pathway analysis found significant differences in purine, taurine, tyrosine, and bile acid metabolites. The VAN group showed a 5-fold decrease in free taurine, a major conjugation substrate of primary bile acids released by bacterial bile salt hydrolases. VAN treatment also decreased fermentation products of aromatic amino acids and amino sugars derived from mucin degradation. Oligosaccharides were the major metabolite class elevated in VAN subjects.ConclusionOur data suggest that RDZ treatment correlates with enhanced preservation of bacteria-derived ligands regulating intestinal immune function and substrates of bacterial metabolism. These metabolic profile differences between a narrow- and broad-spectrum antibiotic may contribute to their varying efficacy in preventing CDI recurrence. Disclosures All authors: No reported disclosures.

1983. Adherence vs. Non-adherence: Clinical Outcomes of an Antimicrobial Stewardship Directed Treatment Protocol for Clostridioides difficile Infection

BackgroundThe 2018 Infectious Diseases Society of America (IDSA) C. difficile infection (CDI) treatment guideline no longer recommends metronidazole as first-line therapy in adults, instead recommending vancomycin or fidaxomicin. At our 1500-bed academic medical center, a new CDI treatment protocol was initiated by the antimicrobial stewardship program (ASP) to guide treatment based on disease severity and risk factors for recurrence. In this study, we compared the clinical cure rate and 30-day recurrence rate in patients who are adherent and non-adherent to our institutional CDI treatment protocol.MethodsPatients with CDI between September-December 2018 were identified using electronic health record (EHR) reports. A retrospective chart review was conducted to collect the following information: baseline demographics, white blood cell count, CDI severity, and risk factors, etc. Outcome measures included clinical cure rate, 30-day recurrence rate, and global cure rate, stratified by whether treatment was adherent or non-adherent to institutional protocol. Student’s t-test was used for continuous variables. Fisher exact test or Chi-square test was used for categorical variables.ResultsA total of 188 patients (adherent group n = 100; non-adherent group n = 88) were included. Patient demographics and baseline risk factors did not differ between groups. Clinical cure rate was higher in adherent group (P < 0.05), while no significant differences were observed in recurrence and global cure rates between the two groups (Figure 1). The overall protocol adherence rate was 53%. The most common reasons for non-adherence are inappropriate vancomycin dose for fulminant CDI (69%) and insufficient duration of treatment (27%).ConclusionAn ASP directed new CDI treatment protocol was successfully implemented at our institution. Patients treated according to our institutional protocol resulted in a higher overall cure rate than those non-adherent. Global cure and 30-day recurrence rates were similar. An overall protocol adherence rate of 53% is consistent with previously published literature. Future direction to develop an EHR order set with targeted recommendations is anticipated to further improve adherence and clinical outcomes. Disclosures All authors: No reported disclosures.