Use Of Oral Vancomycin Research Articles

When it rains it pours: An increased prevalence of intestinal carriage of vancomycin-resistant Enterococcus faecium related to higher use of oral vancomycin in a tertiary care Hungarian clinical centre during the years of the COVID-19 pandemic

ObjectivesThis study aims to investigate the association between oral vancomycin consumption and intestinal vancomycin-resistant Enterococcus carriage in the pre- and COVID era in the clinical centre of the University of Szeged, Hungary. MethodsThis retrospective microbiological examination was carried out using electronically collected data, corresponding to the period between 1 January 2018 and 31 December 2022, at the Department of Medical Microbiology. Data included isolated species and the according antimicrobial susceptibility patterns. Annual consumption data for oral vancomycin consumption were exported from the database of the central pharmacy of the clinical centre. As a strain typing procedure, Fourier transform infrared spectroscopy analysis was used. ResultsThere was a significant increase in the number of faecal vancomycin-resistant Enterococcus isolates throughout the study. The prevalence increased significantly during the years of the pandemic. The use of orally administered vancomycin in the clinical centre increased significantly. A strong positive correlation existed between the two phenomena. Several strains with different resistance patterns spread in the clinical centre. Two of these occurred in greater numbers, differing in their high-level aminoglycoside resistance. However, the overall resistance of these strains was stagnating. FTIR analysis revealed that 59 of the 62 strains were also divided into 2 large clusters differing partially in their high-level aminoglycoside resistance. ConclusionsDuring the pandemic, intestinal VRE carriage among clinical centre patients increased significantly, linked to increased oral vancomycin use. Different strains spread, with aminoglycoside resistance being the primary distinction. This highlights the negative impact of the pandemic on VRE carriage.

Reply: Insurance should cover vancomycin for primary sclerosing cholangitis.

Ali and colleagues raise issues of insurance coverage for oral vancomycin (OV) for the treatment of primary sclerosing cholangitis (PSC); however, the purpose of AASLD guidance statements is to help clinicians understand and implement the most recent evidence (https://www.aasld.org/practice-guidelines). The writing group, Practice Guidance Committee, and AASLD Governing Board and supported the final statement that there is insufficient evidence to recommend the use of OV which is consistent with the 2022 European Association for the Study of the Liver guidelines.1 The meta-analysis referred to included only 2 randomized controlled trials of OV.2. The largest study randomized 29 patients to OV or placebo for 12 weeks and reported an improvement in Mayo Risk Score, though total bilirubin did not change. The other randomized controlled trials was not placebo-controlled and included 8 and 9 patients who received low or high doses of OV, respectively, for 12 weeks. Compared with baseline, alkaline phosphatase decreased in both groups, and Mayo Risk Score decreased only in the low-dose group, but without change in total bilirubin. A third study was open-labeled and reported on 30 enrolled subjects and 29 patients treated outside protocol, 25 (42%) of whom had small duct PSC, and several previously treated with OV.3 The methods used to support the claims of imprvements in histology and cholangiograms were not reported. In contrast, a retrospective study of 264 patients found that neither OV nor ursodiol were associated with clinical improvements compared with observation in pediatric patients with PSC.4 Thus, the data supporting the use of OV in PSC is not “robust” and the statements Ali an colleagues made about OV are not supported by current evidence. More concerning is the suggestion that OV might be a substitute for biologics for treating inflammatory bowel disease. Management of PSC-associated inflammatory bowel disease was outside the scope of the Guidance, but multiple society guidelines do not recommend vancomycin for acute severe ulcerative colitis. All stakeholders desire a safe and effective treatment for PSC. Ali and colleagues believe that OV is that treatment, but current evidence does not support this belief.

406. Vancomycin Activity against Clostridioides difficile Over Three Decades in Chicago

Abstract Background In 2017, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiologist of America (SHEA) updated the C. difficile (CD) treatment guidelines recommending vancomycin as the preferred therapy for C. difficile infections (CDI). We assessed the in vitro vancomycin minimum inhibitory concentration (MIC) against CD across three decades to determine if the vancomycin MIC had increased since these guidelines were published. Methods We performed antimicrobial agar dilution susceptibility testing on 89 clinically relevant CD isolates collected within Chicagoland area. These isolates were selected from 3 separate timeframes: 2005 – 2007, 2013 – 2015, and 2021. Isolates were selected based on the prevalence of restriction endonuclease analysis (REA) strain types within each time cohort. Treatment response to vancomycin was reviewed for patients from the 2021 cohort if CD isolates had a vancomycin MIC of ≥ 16 μg/ml. Results The in vitro vancomycin geometric mean MIC against all 89 CD isolates was 2.53 μg/ml with a MIC50 of 2 μg/ml and MIC90 of 4 μg/ml. Comparing the 3 timeframes, the geometric mean vancomycin MICs from 2005-2007, 2013-2015, and 2021 were 2.35, 2.27, and 2.91, respectively (p=0.11). Comparison of the isolates collected from 2005 – 2015 to 2021, the in vitro vancomycin geometric mean MICs were 2.31 and 2.91, respectively (p = 0.037). REA group BI was the most common strain group to have an increased in vitro vancomycin MIC within the 2021 cohort as 4 of the 5 isolates tested had a MIC of 16 μg/ml. All 4 of the patients infected with these strains with an elevated vancomycin MICs were treated vancomycin. All 4 patients had a resolution of symptoms on vancomycin and 2 suffered from a recurrent infection within ≤4 weeks of completing vancomycin. Conclusion The vancomycin MIC against CD has trended upwards slightly over the past 20 years. The most notable change occurred between 2015 and 2021. We hypothesize that this increase is due to increased use of oral vancomycin for the treatment of CDI. However, these data indicate that most isolates still have a MIC of ≤4 μg/ml and an elevated MIC does not appear to impact clinical outcomes. Further study is required to determine if this upward trend in vancomycin MIC continues and if this could have any potential clinical implications. Disclosures Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant.

213. Prophylactic oral vancomycin for Clostridioides difficile in allogeneic hematopoietic stem cell transplant recipients

Abstract Background Allogeneic hematopoietic stem cell transplant (alloHSCT) recipients are at substantial risk for Clostridioides difficile infection (CDI) due to prolonged hospitalization and alteration of the intestinal mucosa and gut microbiota from conditioning regimens, antimicrobials, and immunosuppressants. CDI in alloHSCT recipients has also been associated with higher rates of acute graft versus host disease (aGVHD). Review of the literature revealed that three institutions have published studies demonstrating oral vancomycin prophylaxis prevents CDI. However, more studies are needed to evaluate the impact of prophylaxis on CDI incidence, resistant infections, and other transplant-related outcomes. Methods We conducted a retrospective review to compare the effectiveness of prophylactic oral vancomycin versus no prophylaxis in 40 alloHSCT recipients in the prevention of CDI at our institution. The prophylactic intervention was initiated June 2020, and 20 patients have undergone alloHSCT as of April 2022. Patients received twice daily oral vancomycin starting the day of admission for transplant until discharge. The prophylaxis group was compared to a control group of 20 consecutive alloHSCT recipients prior to initiation of the intervention. The primary outcome was the incidence of CDI. Secondary outcomes included incidence of vancomycin resistant enterococcus (VRE) infection and incidence of aGVHD. Results During admission for transplant and at +100 days post-transplant, 5/20 (25%) of patients in the control group developed CDI compared to 0/20 (0%) in the prophylaxis group (p=0.0471). Prophylaxis was not associated with higher rates of VRE infection through day +100 post-transplant (2/20, 10% vs 0/20, 0%, p=0.487). Use of oral vancomycin was not associated with increased incidence of aGVHD, which occurred in 10/20 (50%) of patients in the control group versus (7/20) 35% in the prophylaxis group (p=0.523). Conclusion Prophylaxis with oral vancomycin was associated with a significant reduction in CDI. Use of prophylaxis was not associated with an increased risk for VRE infection and there was no change in incidence of aGVHD. Our review supports the use of prophylaxis, and we will continue to monitor for resistant infections and evaluate the impact on survival. Disclosures Alfred Luk, MD, Karius: Grant/Research Support.

Clostridioides difficile Infection Treatment and Outcome Disparities in a National Sample of United States Hospitals.

Clostridioides difficile infection (CDI) disproportionately affects certain populations, but few studies have investigated health outcome disparities among patients with CDI. This study aimed to characterize CDI treatment and health outcomes among patients by age group, sex, race, and ethnicity. This was a nationally representative, retrospective cohort study of patients with laboratory-confirmed CDI within the Premier Healthcare Database from January 2018 to March 2021. CDI therapies received and health outcomes were compared between patients by age group, sex, race, and Hispanic ethnicity using bivariable and multivariable statistical analyses. A total of 45,331 CDI encounters were included for analysis: 38,764 index encounters and 6567 recurrent encounters. CDI treatment patterns, especially oral vancomycin use, varied predominantly by age group. Older adult (65+ years), male, Black, and Hispanic patients incurred the highest treatment-related costs and were at greatest risk for severe CDI. Male sex was an independent predictor of in-hospital mortality (aOR 1.17, 95% CI 1.05–1.31). Male sex (aOR 1.25, 95% CI 1.18–1.32) and Black race (aOR 1.29, 95% CI 1.19–1.41) were independent predictors of hospital length of stay >7 days in index encounters. In this nationally representative study, CDI treatment and outcome disparities were noted by age group, sex, and race.

Clostridioides difficile Infection in Hospitalized Pediatric Patients: Comparisons of Epidemiology, Testing, and Treatment from 2013 to 2019

To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to2019. The Pediatric Health Information Systemdatabase was queried for patient admissions (age 0-17years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment. We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 cases per 10 000 patient-days (95% CI, 4.03-5.93) in 2019 (P<.001). C difficile-specific testing also decreased during the study period (P<.001). Chronic gastrointestinal conditions (36%) and malignancy (32%) were the most common comorbidities in CDI encounters. Oral metronidazole use decreased during the study period (P<.01) and oral vancomycin use increased (P<.001). Our study demonstrates a decrease in CDI incidence in hospitalized pediatric patients, a notable change from prior studies, although this may have been influenced by altered testing patterns. We found a high incidence of CDI in patients with cancer and gastrointestinal conditions: groups that warrant targeted evaluation of CDI prevention and treatment.

Concurrent and Subsequent Co-Infections of Clostridioides difficile Colitis in the Era of Gut Microbiota and Expanding Treatment Options.

We narratively reviewed the physiopathology, epidemiology, and management of co-infections in Clostridioides difficile colitis (CDI) by searching the following keywords in Embase, MedLine, and PubMed: “Clostridium/Clostridioides difficile”, “co-infection”, “blood-stream infection” (BSI), “fungemia”, “Candida”, “Cytomegalovirus”, “probiotics”, “microbial translocation” (MT). Bacterial BSIs (mainly by Enterobacteriaceae and Enterococcus) and fungemia (mainly by Candida albicans) may occur in up to 20% and 9% of CDI, increasing mortality and length of hospitalization. Up to 68% of the isolates are multi-drug-resistant bacteria. A pivotal role is played by gut dysbiosis, intestinal barrier leakage, and MT. Specific risk factors are represented by CDI-inducing broad-spectrum antibiotics, oral vancomycin use, and CDI severity. Probiotics administration (mainly Saccharomyces and Lactobacillus) during moderate/severe CDI may favor probiotics superinfection. Other co-infections (such as Cytomegalovirus or protozoa) can complicate limited and specific cases. There is mounting evidence that fidaxomicin, bezlotoxumab, and fecal microbiota transplantation can significantly reduce the rate of co-infections compared to historical therapies by interrupting the vicious circle between CDI, treatments, and MT. Bacterial BSIs and candidemia represent the most common co-infections in CDI. Physicians should be aware of this complication to promptly diagnose and treat it and enforce preventive strategies that include a more comprehensive consideration of newer treatment options.

Use of oral vancomycin in children with autoimmune liver disease: A single centre experience.

BACKGROUNDPrevious reports showed some beneficial effect of oral vancomycin treatment (OVT) in children with primary sclerosing cholangitis; conversely, the experience in patients with other autoimmune liver diseases (AILD), including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), is scant. AIMTo assess the response to immunosuppressive treatment (IS) and to OVT in children diagnosed with AILD.METHODSRetrospective study of children diagnosed with AIH (normal biliary tree at cholangiography) and ASC (abnormal biliary tree at cholangiography) in the last 10 years. All underwent standard immunosuppressive therapy (IS), but non-responders received also OVT. Biochemical remission [normal aspartate aminotransferase (AST)] and immunological remission (normal IgG and negative autoantibodies) rates and Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) index were assessed and compared during the follow up.RESULTS75 children were included [69% female, median age 10.5 years (5.6-13.4 years), AIH = 54, ASC= 21]. Sixty-three patients (84%, AIH = 52, ASC = 11) were treated with standard IS and 61 achieved biochemical remission, whereas 12 not responding to IS [16%, F = 75%, median age 13.5 years, (12.2-15.7), 10 with ASC] required OVT and 8 achieved biochemical remission. Overall OVT increased the biochemical remission rate of the whole group of AILD patients from 81% (61/75) to 92% (69/75). Median values of AST, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) decreased significantly after OVT start (P < 0.05). Complete normalization of livers enzymes (AST, ALT and GGT) was observed in 6/12 patients (50%). Decrease in SCOPE index score was reported in 5/12 patients (42%). At last follow up (median of 4.4 years, range 0.6-13.8 years) all 75 patients are alive, 6 (8%, 1 with ASC) successfully discontinued medications, 1 (with ASC) required liver transplantation.CONCLUSIONChildren with AIH and ASC respond well to IS treatment. OVT may represent a valuable treatment option to achieve biochemical remission in patients not responding to standard IS. These promising preliminary results suggest that a prospective study is indicated to define the efficacy of OVT in AILD.

763. Impact of Two-Step Testing Algorithm on Hospital-onset Clostridioides difficile Infections and Oral Vancomycin Prescription Practices at an Academic Medical Center

Background Clostridioides difficile infection (CDI) is one of the leading causes of hospital –onset (HO) infections. Clinically distinguishing true CDI versus colonization with C.difficile is challenging. We implemented a two-step testing algorithm to discriminate true CDI from colonization then evaluated the effect on rate of HO CDI and oral vancomycin. MethodsIn May 2020, a two-step testing algorithm was implemented utilizing C. difficile PCR and enzyme immunoassay (EIA) glutamate dehydrogenase (Figure 1). Rates of HO CDI and use of oral vancomycin was compared in the three quarters preceding and after this intervention (July 2019-March 2020 and July 2020-March 2021, respectively). HO CDI was defined based on National Healthcare Safety Network (NHSN) Laboratory Identified (LabID) event as last positive C.difficile test result performed on a specimen collected >3 calendar days after admission to the facility. HO CDI rates were assessed based on Standardized Infection Ratio (SIR) data and antimicrobial use was reported in days of therapy (DoT) per 1000 patient days. Figure 1. Two-Step Testing Algorithm for Diagnosing Clostridioides difficile infection ResultsDuring the pre-intervention period 30 HO CDI cases were reported compared to 9 cases in the post-intervention period (p=0.02) (Figure 2). There was a non-statistically significant reduction in CDI SIR in post-intervention period (0.133 vs. 0.305, p=0.11). Oral vancomycin use was similar in the pre- and post-intervention periods (3.89 vs. 3.84, p=0.96). Fidaxomicin use was rare (< 0.2 DoT/1000 pt days). Of 26 HO C.difficile colonized patients in post-intervention period, 14 (54%) patients received oral vancomycin treatment. Infectious diseases was consulted on 7/14 and recommended discontinuation of treatment in 3 while treatment was continued for other patients based on clinical status and immunocompromising conditions. Figure 2. Comparison of pre- and post-intervention trend in Hospital-onset CDI rate ConclusionWe successfully reduced our HO CDI infections and SIR below national average after implementation of two-step testing algorithm for CDI. There was no impact on the rate of oral vancomycin use. We observed at 54% rate of treatment for patients categorized as likely colonization. Provider education and stewardship interventions are necessary to reduce inappropriate use of oral vancomycin in colonized patients. Disclosures All Authors: No reported disclosures

Changes in Metronidazole and Vancomycin Utilization for Nonsevere Clostridioides difficile Infection Among Institutions Caring for Children.

Clostridioides difficile infection guidelines were published in final format on April 1, 2018. Among 4962 and 3545 C. difficile infection cases in children the year before and after publication, oral metronidazole use decreased from 63.0% to 44.3% (P < 0.001) and oral vancomycin use increased from 27.3% to 47.7% (P < 0.001). Quarterly metronidazole utilization decreased postguidelines among 117 institutions, incidence rate ratios 0.86 (95% confidence intervals: 0.78-0.96).

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

Impact of a Clostridioides Difficile Testing Computerized Clinical Decision Support Tool on an Adult Stem Cell Transplantation and Hematologic Malignancies Unit

Clostridioides difficile infection rates are higher in hospitalized hematopoietic stem cell transplantation (HSCT) recipients and patients with hematologic malignancy (HM) compared with the general population. This is related both to extensive exposure to antibiotics as well as to frequent and often prolonged hospitalization. In this population, with numerous potential causes of diarrhea, a subset of C difficile detected is presumed to represent colonization rather than clinical infection. The use of decision support tools to guide ordering in hospitalized patients has been reported to decrease both C difficile testing and detection rates. Following implementation of a computerized decision support tool on our HSCT/HM unit, we observed a >2-fold decrease in C difficile testing volume and National Healthcare Safety Network-defined laboratory identifications of C difficile. Furthermore, the rate of oral vancomycin use, as well as the incidence of vancomycin-resistant enterococci colonization and bloodstream infection, decreased in the postintervention period.

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.

Universal molecular Clostridioides difficile screening and overtreatment in solid organ transplant recipients.

Screening for Clostridioides difficile (CD) colonization can be performed using molecular testing to identify the presence of microbial DNA of the toxin gene. Colonization rates for hospitalized patients are as high as 20% and may be considerably higher in solid organ transplant (SOT) recipients. Treatment for CD should be based on clinical disease and not colonization, yet clinicians may misinterpret a positive CD screen resulting in overtreatment. The objective of this analysis is to determine how often positive CD screens resulted in inappropriate treatment with oral vancomycin. Clostridioides difficile screens were performed using the XpertCdifficileassay (Cepheid), a nucleic acid amplification testing method utilizing polymerase chain reaction (PCR), on peri-rectal swabs for newly admitted patients. This was a single-center cohort study of adult patients with CD screens hospitalized between July 2015 and November 2018. The primary outcome was the rate of inappropriate oral vancomycin treatment in all patients and in SOT recipients, defined as therapy in the absence of diarrhea. Of the 47076 total CD screens reviewed, 1,921 were positive. In the SOT cohort, 58 of 329 screens were positive (4.1% vs 17.9%, P<.01). Of all patients with a positive CD screen, 20.1% (386/1921) were treated with oral vancomycin within 48hours of swab collection. In the SOT cohort, 39.6% (23/58) with positive CD screens were treated with oral vancomycin within 48hours. Of the SOT patients who received oral vancomycin, 39% (9/23) did not have true CD infection. Solid organ transplant recipients were more likely to have CD colonization detected by peri-rectal screening than the general inpatient population. SOT and non-SOT patients were treated with oral vancomycin at similar rates in response to the positive screen. Nearly half of the oral vancomycin use in SOT recipients was likely overtreatment, but this finding is limited by the low number of patients in this cohort.

Treatment of Clostridioides difficile Infection and Non-compliance with Treatment Guidelines in Adults in 10 US Geographical Locations, 2013-2015.

Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) guidelines describe recommended therapy for Clostridioides difficile infection (CDI). To describe CDI treatment and, among those with severe CDI, determine predictors of adherence to the 2010 IDSA/SHEA treatment guidelines. We analyzed 2013-2015 CDI treatment data collected through the Centers for Disease Control and Prevention's Emerging Infections Program. Generalized linear mixed models were used to identify predictors of guideline-adherent therapy. A CDI case was defined as a positive stool specimen in a person aged ≥ 18 years without a positive test in the prior 8 weeks; severe CDI cases were defined as having a white blood cell count ≥ 15,000 cells/μl. Prescribing and predictors of guideline-adherent CDI therapy for severe disease. Of 18,243 cases, 14,257 (78%) were treated with metronidazole, 7683 (42%) with vancomycin, and 313 (2%) with fidaxomicin. The median duration of therapy was 14 (interquartile range, 11-15) days. Severe CDI was identified in 3250 (18%) cases; of 3121 with treatment data available, 1480 (47%) were prescribed guideline-adherent therapy. Among severe CDI cases, hospital admission (adjusted odds ratio [aOR] 2.48; 95% confidence interval [CI] 1.90, 3.24), age ≥ 65 years (aOR 1.37; 95% CI 1.10, 1.71), Charlson comorbidity index ≥ 3 (aOR 1.27; 95% CI 1.04, 1.55), immunosuppressive therapy (aOR 1.21; 95% CI 1.02, 1.42), and inflammatory bowel disease (aOR 1.56; 95% CI 1.13, 2.17) were associated with being prescribed guideline-adherent therapy. Provider adherence to the 2010 treatment guidelines for severe CDI was low. Although the updated 2017 CDI guidelines, which expand the use of oral vancomycin for all CDI, might improve adherence by removing the need to apply severity criteria, other efforts to improve adherence are likely needed, including educating providers and addressing barriers to prescribing guideline-adherent therapy, particularly in outpatient settings.

Does oral vancomycin use necessitate therapeutic drug monitoring?

Oral vancomycin use has generally increased as a consequence of the need to treat and/or prevent Clostridium (Clostridiodes) difficile-associated disease (CDAD). This review examines the cumulative scientific evidence that guides therapeutic monitoring of oral vancomycin therapy. The existing publications were reviewed from the time of the drug's inception to July 2019. This review utilized access as available in PubMed, EMBASE, CINAHL Plus, and the Cochrane Library. Case reports and small patient series have documented anecdotal-associated elevations in serum levels. Correlation of absorbed vancomycin with subsequent toxicity is difficult to determine, but serum levels approaching those obtained after parenteral administration have raised concern. Prolonged usage and total dosing over 500mg/day among adult age ranges have been associated with accumulation. In addition, risk factors for vancomycin accumulation systemically after oral dosing include renal compromise, combined oral and other enteral therapy, severe CDAD, other intercurrent bowel inflammation, polypharmacy, and increased patient complexity/morbidity. Until systemic toxicity from oral vancomycin absorption is better understood, individual considerations should be made for therapeutic serum monitoring during oral vancomycin treatment. Therapeutic drug monitoring is suggested for several high-risk situations in which high blood levels may be anticipated.

2360. Impact of a Two-Step Antimicrobial Stewardship Intervention on C. difficile Infection Diagnosis at an Urban Veteran’s Affairs Medical Center

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.MethodsThis 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).ResultsCompared 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).ConclusionProvider 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.

2415. Oral Vancomycin for Secondary Prophylaxis of Clostridium difficile Infections among High-risk Patients

Background Clostridium difficile infection (CDI) is associated with high rates of recurrence, and major risk factors for recurrence include prior CDI episode(s) and antibiotic exposure. Prior studies concluded a reduction in CDI recurrence using oral vancomycin for prophylaxis (ppx), but were limited by prescriber bias and inclusion of all hospitalized adult patients with prior CDI and receipt of systemic antibiotics. We sought to determine whether or not oral vancomycin prophylaxis reduced CDI recurrence in high-risk patients.MethodsThis retrospective cohort study included patients > 2 years of age who had at least 2 episodes of CDI within the last year prior to broad-spectrum antibiotic exposure. The ppx cohort included patients who received oral vancomycin for > 50% of the duration of broad-spectrum antibiotic therapy, and the no ppx cohort included patients who received no oral vancomycin while on broad-spectrum antibiotics. Cohorts were compared via a univariate analysis. A Kaplan–Meier analysis was used to evaluate the time-to-event for development of CDI.ResultsOf 108 patients who met inclusion criteria, 88 patients were included in the no ppx cohort and 20 patients in the ppx cohort. The primary outcome of CDI incidence was numerically lower in the ppx cohort [13 (14.8%) vs. 2 (10%), p = 0.733]. Secondary outcomes within 12 weeks of broad-spectrum antibiotic initiation were similar between cohorts. The mean time from broad-spectrum antibiotic initiation to CDI recurrence was longer among the ppx cohort, suggesting a delay in time to CDI recurrence (29 + 25.9 vs. 57.5 + 26.1 days, p = 0.171). This delay led to a lower incidence of hospital acquired (HA) CDI in the ppx cohort [4 (30.8%) vs. 0 (0%), P > 0.99]. The Kaplan–Meier analysis (Figure 1) demonstrated no significant difference in time-to-event of CDI, p = 0.70.ConclusionThe use of oral vancomycin for secondary ppx of CDI was not shown to have a statistically significant difference in CDI recurrence compared with no ppx in this study. However, this may be due to the low sample size in the ppx cohort and low CDI event rates. The trend toward a delay in CDI recurrence and reduction in HA-CDI with the use of oral vancomycin is hypothesis generating. Further controlled studies are warranted to confirm the role of oral vancomycin for secondary ppx of CDI. Disclosures All authors: No reported disclosures.

2412. Oral Vancomycin Prophylaxis Against Recurrent Clostridioides difficile Infection: Efficacy and Side-effects: Two Hospitals Experience

Background Clostridioides difficile is the most common hospital-acquired pathogen with an unchanged infection prevalence between 2011–2015. The data regarding the effectiveness of chemical prophylaxis to prevent recurrent C. difficile infection (CDI) are conflicting.MethodsWe conducted a retrospective study of hospitalized patients with CDI history in 2 New York academic hospitals over a 4.5-year period to determine the effectiveness of vancomycin prophylaxis for CDI prevention. The participating hospitals implemented an automated alert to providers recommending oral vancomycin 125 mg twice daily in patients with a history of CDI scheduled to receive any systemic antimicrobials for the duration of therapy and 5 days thereafter. Measured outcomes included the rate of breakthrough and recurrent CDI, defined as CDI during and in the one-month following prophylaxis, respectively. A self-controlled, before and after study design was employed to examine whether the use of oral vancomycin was associated with an increase in the prevalence of vancomycin-resistant Enterococcus species (VRE) both in absolute numbers and in comparison to vancomycin-sensitive Enterococcus species (VSE) in the period following vancomycin prophylaxis.Results264 patients were included in the final analysis. Breakthrough CDI was identified in 17 (6.4%; 95% CIs 3.8%–10.1%) and recurrent CDI in 22 (8.3%; 95% CIs 5.3%–12.3%) patients. Of the 102 patients with a history of CDI within the 3 months preceding the administration of prophylaxis 4 (3.9%, 95% CIs 1.1%-9.7%) had breakthrough CDI and 9 had recurrent disease (8.3%, 95% CIs 5.3%–12.3%). In the 3 months following vancomycin prophylaxis there was an increase in both the absolute number of VRE and the ratio of VRE to VSE isolates compared with the combined period of 1.5 months preceding and the 3–4.5 months following the administration of prophylaxis. The increase in the absolute number of VRE colonized patients remained in the extended period of 6 months following prophylaxis.ConclusionProphylactic vancomycin is an effective strategy to prevent CDI recurrence, but is associated with an increase in VRE colonization in the immediate period after administration. The risk of VRE infection should lead to careful selection of patients at the highest risk for CDI recurrence.Disclosures All authors: No reported disclosures.

184 Cost-Effective Analysis of Prophylactic Oral Vancomycin Use to Prevent Recurrent Clostridium difficile Infections in Hospitalized Patients

INTRODUCTION: Clostridium difficile infections (CDI) is the single largest cause of morbidity and mortality among hospital acquired infections and is characterized by frequent recurrence. In the hospital setting, CDI tends to occur in patients with predisposing risk factors such as advanced age, prolonged stay, and exposure to systemic antibiotics. Although antimicrobial agents are major risk factors for CDI, their use in patients is often necessary and inevitable. There is an emerging practice of giving prophylactic oral vancomycin as secondary prophylaxis to prevent recurrent CDI. Prior published retrospective cohort studies suggest patients on systemic antimicrobial therapy who received prophylactic oral vancomycin had significantly lower rates of recurrent CDI compared to patients who did not receive the prophylaxis. However, the cost effectiveness of oral vancomycin used as secondary prophylaxis to prevent recurrent CDI is unknown. METHODS: We programmed a Markov Chain Monte Carlo simulation analytic model using published literature and national databases. For each scenario, 500 patients were simulated. The base case was modeled as a hypothetic cohort of hospitalized patients with a history of CDI, currently receiving systemic antimicrobial therapy, who either received or did not receive secondary prophylactic oral vancomycin. Projected outcomes included cost (US dollars). 2-way sensitivity analyses were conducted. A P-value less than 0.05 was considered significant. RESULTS: Across 500 simulations, prophylactic oral vancomycin resulted in a greater cost compared to no oral vancomycin at $12,045.67, 95% CI = [11880.80–12210.53] and $8,135.48, 95% CI = [8,047.37–8,223.58], respectively (Figure 1). The difference was statistically significant (P value &lt;1 × 10−6). The treatment arm with oral vancomycin also resulted in approximately a 2.45 increased risk of mortality compared to patients who did not receive vancomycin. CONCLUSION: Our findings suggest that prophylactic oral vancomycin may not be a cost-effective strategy in reducing the incidence of CDI recurrence and may, in fact, be associated with an increased risk of mortality in hospitalized patients receiving high dose systemic antimicrobial therapy. These findings appear to be largely driven by the risk of developing vancomycin resistant enterococcus (VRE) infections, namely VRE bacteremia which is associated with high economic burden and increased mortality.