ImportanceA safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.ObjectivesTo evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.Design, Setting, and ParticipantsThis phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry.InterventionsSER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI.Main Outcomes and MeasuresThe main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population.ResultsOf 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]).Conclusions and RelevanceIn this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI.Trial RegistrationClinicalTrials.gov identifier: NCT03183141

Infection due to enterohemorrhagic Escherichia coli (EHEC) has not been described in immunosuppressed patients. We recently saw a case of EHEC infection caused by a novel Shiga toxin II-producing Escherichia coli serotype (O121:H19) that caused hemorrhagic colitis in a patient with renal and cardiac transplants. The patient's signs, symptoms, and colon pathology were similar to reports of EHEC infection in immunocompetent patients. This case suggests that the immunosuppressed state may not alter the clinical presentation or histopathologic findings of this disorder. Assays for EHEC are not routinely done at most hospitals. Therefore, clinicians caring for transplant patients should be aware of the typical clinical presentation of EHEC infection, so that they can initiate appropriate laboratory investigation in suspected cases.

Background Outpatient parenteral antimicrobial therapy (OPAT) has been shown to be safe and effective for self-administration but can lead to non-adherence without supervision. A physician office infusion center (POIC) with pharmacy services provides a unique opportunity to impact adherence and OPAT management. Patients (pts) typically come to the POIC weekly for catheter care, laboratory collection, medication pick-up and as needed provider visits. Often, close provider oversight allows for de-escalation of OPAT. We evaluated adherence to therapy, visits and associated cost saving in pts receiving self-administered OPAT through POICs. Methods Pts receiving home OPAT in 2021 were randomly selected from participating sites based on annual pt volume. Adherence was assessed as % of OPAT doses dispensed vs. doses missed. Frequency of office visits for routine catheter care and labs along with OPAT completion were collected. Cost savings were calculated in days of OPAT saved due to therapy de-escalation and response to therapy, based upon published daily costs of OPAT. Pt characteristics, OPAT duration, infection type and regimen were captured. Results A total of 125 of 2180 pts from 13 POICs nationally were included (mean age 50±18 years, 52% male). Mean OPAT duration was 38±9 days. Predominant infections were bone and joint (38%), complicated skin (18%), intra-abdominal (15%) and bacteremia (14%). The most common antimicrobials were cephalosporins (54%) with 20 pts self-administering ≥2 drugs. Pts had a mean of 6±3 POIC visits during the therapy course with completion as scheduled in 703/706 visits (99.6%). OPAT was completed as planned in 118 pts (94%), with discontinuations for adverse events (n=3), hospitalization (n=2), or non-adherence (n=2). Overall adherence rate was 99.3% with 51 missed of 7315 doses dispensed. De-escalation during OPAT saved 533 doses equating to 307 days of OPAT (2.4 days/pt). Based on an average daily OPAT cost of $140, this saved $42,980 in the randomized cohort and an estimated $749,571 annually in the entire population. Conclusion Home OPAT through an ID POIC was associated with a very high rate of adherence and compliance to scheduled visits in pts. ID oversight resulted in healthcare cost savings through onsite antimicrobial stewardship and therapy management. Disclosures Lucinda J. Van Anglen, PharmD, Merck & Co.: Grant/Research Support|Paratek: Grant/Research Support.

Background AmpC β-lactamase enzymes can be produced by a number of Enterobacterales. Due to its inducible chromosomal resistance, cefepime is often preferred. In vitro analysis and clinical reports have shown AmpC expression can occur less than 5% among S. marcescens. Locally, there has been a rise in beta-lactam resistant S. marcescens, however guidelines and small clinical trials have suggested treatment according to susceptibility testing. This study aimed to evaluate the use of cefepime vs. alternative beta-lactams like third generation cephalosporins or piperacillin-tazobactam as treatment of S. marcescens. Overall treatment Failure Methods This is a single-center, retrospective review of adult hospitalized patients with S. marcescens BSIs over a five-year period. Patients who received more than 24 hours of susceptible antibiotics were included. Patients who received at least 72 hours of antibiotics from index blood culture were divided into definitive cefepime (DCEF) or definitive alternative beta-lactams (DBLA) groups. Composite outcome of 30-day re-admission, 90-day reinfection rates, and mortality was used to evaluate treatment failure. Results A total of 53 patients were enrolled. Common sources of infection include genitourinary (12), bone and joint (6), and skin and soft tissue (6). DCEF and DBLA groups included 35 and 18 patients, respectively. Most DBLA patients received piperacillin-tazobactam (9/18). Median Charlson Comorbidity Index (CCI) was 6 for DCEF and 4.5 for DBLA. 11 patients in the DCEF group were readmitted, vs 2 patients in the DBLA group. One patient in each group had reinfection within 90 days. In-hospital mortality occurred in 4 and 1 patients in the DCEF and DBLA groups, respectively. Overall treatment failure was observed in 15 patients in the DCEF group and 3 patients in the DBLA group. Median hospital length of stay was 10.1 days for DCEF and 9.5 days for DBLA. Conclusion More patients received DCEF compared to DBLA, potentially related to acuity evidenced by higher CCI and ICU admissions. Results showed a higher rate of overall treatment failure among DCEF group. Due to the retrospective design and small sample size, it is difficult to infer clinical significance. These findings prompt further investigation into the difference in treatment failure between these groups. Disclosures All Authors: No reported disclosures.

Background Oral antibiotic stepdown therapy for Gram-negative (GN) bloodstream infection (BSI) appears to be a safe option, though high bioavailability drugs like fluoroquinolones (FQ) and trimethoprim-sulfamethoxazole are often recommended without clear evidence demonstrating superiority. Due to increasing concerns of FQ resistance and collateral damage with an increasing community C. difficile rate, our organization sought to reduce overall FQ use and a shift toward oral beta-lactams (BL) was observed. A review was conducted to assess the outcomes of this shift. Methods This retrospective cohort included all patients within our 3-hospital system who had a positive GN blood culture and were transitioned to oral therapy to complete treatment outpatient for bacteremia between Jan 2017-Sept 2019. The primary outcome was recurrent BSI within 30 days of completing initial treatment. Secondary outcomes included 30-day mortality, 30-day recurrence of organism at an alternate source, 30-day readmission, and 90-day BSI relapse. Results Of 191 GN BSIs, 77 patients were transitioned to oral therapy. The mean age was 68 years, 60% were female. The most common source of infection was described as urine (39/77), intra-abdominal (16/77), unknown (13/77). Mean total antibiotic duration (IV plus PO) was 14 days (range 7–33). Patients received an average of 5 days IV prior to transitioning to PO therapy. The most common PO class was a 1st gen cephalosporin (29/77), followed by BL/BL inhibitor (16/77), and a FQ (13/77). There were no 30-day relapse BSIs observed in this cohort. There was 1 patient discharged to inpatient hospice, and no other 30-day mortality observed. There were 4 recurrent UTIs observed within 30 days, none of which required readmission. Of the twelve 30-day readmissions, 1 was considered by the investigators to be related to the initial infection. Conclusion An opportunity for education regarding duration of therapy was identified. Oral beta lactam use in our limited population appears to be a reasonable option to facilitate discharge. Results should be confirmed in additional, larger studies. Disclosures All Authors: No reported disclosures