bluuebunny/crossref_metadata_2025_split huggingface dataset:
636. Meningococcal Vaccination and Antibiotic Prophylaxis Practices in Solid Organ Transplant Recipients undergoing Eculizumab Therapy
Authors: Bhaimia Eric , Yetmar Zachary A , Mahmood Maryam , Stacy Bernard , Stephen Jenise , Vikram Holenarasipur R , Brumble Lisa M 
Published: December 2022

Abstract

Background
Eculizumab, an inhibitor of terminal complement activation, has been utilized in pre-transplant desensitization, treatment of antibody-mediated rejection and thrombotic microangiopathy in solid organ transplant recipients (SOTR). Eculizumab is associated with meningococcal disease, leading to guidelines for vaccination against serogroups ACWY (menACWY) and B (menB) at least 2 weeks prior to eculizumab therapy. In persons requiring emergent use of eculizumab, prophylaxis for at least 2 weeks is recommended. SOTRs respond suboptimally to vaccination, raising consideration for pre-transplant vaccination and prolonged prophylaxis in those undergoing eculizumab therapy. We sought to describe meningococcal vaccination and prophylaxis practices among SOTRs receiving eculizumab.

Methods
We performed a retrospective chart review of meningococcal vaccination, including number and timing pre- or post-transplant, along with prophylaxis prescribing and duration in SOTRs receiving eculizumab across 3 distinct Mayo Clinic Enterprise sites (Rochester, Arizona, and Florida).

Results
200 SOTRs receiving at least one dose of eculizumab between 1/1/2008 and 9/16/2021 were reviewed. Eculizumab indications included antibody mediated rejection (38%), desensitization (26%), and thrombotic microangiopathy (19%). 83% (166/200) of SOTRs received eculizumab for an unanticipated post-transplant complication. Vaccination rates were 82% (164/200) and 35.5% (71/200) for menACWY dose 1 and 2, respectively, and 54% (108/200) and 28.5% (57/200) for menB dose 1 and 2, respectively. The majority received their first vaccination post-transplant: menACWY 66.5% (133/200) and menB 2.5% (185/200). Among those without vaccination pre-eculizumab, 22.3% (41/184) were not prescribed prophylaxis. The median duration of prophylaxis was 62 (range 4-2651) days.

Conclusion
Most SOTRs underwent meningococcal vaccinations near the time of eculizumab administration post-transplant for an unanticipated complication. One-fifth of those meeting criteria were not provided meningococcal prophylaxis. These findings may support pre-transplant administration of meningococcal vaccinations and heightened awareness for meningococcal prophylaxis in SOTRs receiving eculizumab.

Disclosures
All Authors: No reported disclosures.
637. Transplant Candidacy for Persons Living with HIV and End-Stage Renal Disease at MUSC
Authors: Crawford Kyle M , Adekunle Ruth O 
Published: December 2022

Abstract

Background
Persons Living with HIV (PLWH) with chronic kidney disease progress to end-stage renal disease (ESRD) at a faster rate than HIV-negative individuals. Unfortunately, there is increasing data to suggest that PLWH are less likely to be waitlisted. We reviewed the transplant care continuum among PLWH at the Medical University of South Carolina (MUSC).

Methods
This was a retrospective review of PLWH and ESRD who either received care at MUSC Health Care System or were referred for Kidney transplant at MUSC between May 1st, 2012 and December 31st, 2021. Cases were included if a PLWH and ESRD had not died before being referred for kidney transplant, had evidence of pursuit of kidney transplant, and sufficient data of their transplant process were available in the medical record system. Descriptive statistics were used to analyze demographic and clinical characteristics as well as the transplant care continuum of PLWH and ESRD at MUSC.

Results
57 PLWH and ESRD were included in the analysis. Of these, 45 (79%) were referred for kidney transplant (Table 1). The median age at the time of referral was 52 (range 26 - 78), 33 (73%) were males and 42 (93%) were of the Black race. The most common causes of ESRD were Multifactorial (36%), HIV-Associated Nephropathy (24%) and unknown (16%). Almost all patients had hypertension (96%) and 29% of patients had diabetes. Additionally, prevalent comorbidities include psychiatric conditions (53%), history of substance use (43%) and history of tobacco use (36%). Of those referred for kidney transplantation, 32 (71%) started a transplant evaluation, 24 (53%) completed the transplant evaluation, 22 (49%) were waitlisted, and 13 (29%) were transplanted. Common reasons why patients did not complete transplant evaluation included not meeting HIV criteria for transplant (9%), having too many comorbidities (9%), and not completing testing (9%).
Clinical Characteristics of the 45 HIV Patients with ESRD Who Were Referred to Kidney Transplant at MUSC
Clinical Data on Transplant Care Continuum, n = 45

Conclusion
The majority of PLWH with ESRD seen at MUSC were referred for kidney transplant and started the evaluation process. More is needed, though, to assist patients in completing the transplant evaluation process and making it to the transplant waitlist, with the ultimate goal of transplantation.

Disclosures
All Authors: No reported disclosures.
653. Characterizing Antibacterial Regimen Modification, Patient Characteristics, and Outcomes for Patients with Complicated Gram-negative Bacterial Infections
Authors: Yamaki Jason , Dillon Ryan J 
Published: December 2022

Abstract

Background
There are few studies describing the rationale or frequency of empiric or directed therapy treatment modification behaviors among patients with complicated Gram-negative bacterial infections (GNBI). We sought to characterize patient and treatment characteristics, details of regimen modification, and patient outcomes.

Methods
This retrospective chart review included patients, admitted from 1/1/2019-12/31/2020 to Hoag Memorial Hospital, with a complicated GNBI due to an extended spectrum cephalosporin resistant pathogen. We present an interim descriptive analysis of 60 patients: demographics, ABX modifications, rationale and timing for modifications, and patient outcomes. ABX modifications were defined a GNB ABX switched, added, or removed.

Results
The predominant culture sources were urine and bloodstream. ESBL organisms (38%) and Pseudomonas spp (32%) were most common. Inpatient initial empiric therapies included TZP (33%), MEM (20%), and CRO (17%). 32% of patients did not have any modifications to their ABX regimens. For patients where modifications occurred this ranged from 0 to 6 changes. Time to the first modification ranged from 2 – 196 hours. For initial modifications, all were considered escalations, and most were based on preliminary culture results (36%), lack of patient response (28%), additional history review (28%) and decompensation (1.7%). No difference in 30 or 90-day mortality or 90-day readmission was observed for patients that did or did not have ABX modifications.

Conclusion
Many patients experience modification to GNB targeted antibacterials, in almost all cases, rationale for change was documented. In this interim analysis no difference in patient outcomes was observed. However, it is well established that increased duration of therapy and exposure to numerous antibacterial agents can increase healthcare resource utilization and may negatively impact local ecology, respectively.

Disclosures
Jason Yamaki, PharmD, PhD, Merck & Co. Inc.,: Grant/Research Support Ryan J. Dillon, MSc, Merck: Employee|Merck: Stocks/Bonds.
655. Combination Eravacycline Therapy for Carbapenem-Resistant Acinetobacter baumannii Pneumonia
Authors: Jackson Melissa N , Ortwine Jessica , Wei Wenjing , Mang Norman S , Prokesch Bonnie C 
Published: December 2022

Abstract

Background
Acinetobacter baumannii typically causes infections in debilitated, hospitalized patients and is difficult to treat due to multiple virulence factors and the presence of intrinsic and acquired antibiotic resistance mechanisms leading to frequent isolation of multi-drug resistant (MDR) phenotypes. Due to problematic pharmacokinetics and/or dose-limiting toxicities of salvage agents, combination therapy with aminoglycosides, ampicillin/sulbactam, polymyxins, minocycline, or tigecycline, is often used. Eravacycline has demonstrated greater in-vitro potency against A. baumannii compared to other tetracycline derivatives making it potentially the more appealing option. However, its utility is hindered by a lack of data supporting pharmacodynamic targets and adequate dosing strategies for CRAB. The goal of this case series was to describe our experience with the use of combination eravacycline therapy for the treatment of CRAB pneumonia.

Methods
This case series included all patients ≥ 18 years of age, diagnosed with SARS-CoV-2, ≥ 1 sputum culture positive for CRAB and a clinical diagnosis of new bacterial pneumonia, who received at least one dose of eravacycline between April 1st and October 1st, 2020. The primary outcome was clinical resolution of CRAB pneumonia. Secondary outcomes evaluated microbiological resolution, need for extended durations of therapy, and frequency of re-starting CRAB therapy within 48 hours of completion.

Results
In total, 25 patients were included in this case series. The median duration of combination therapy was 10 days. Most patients (96%) received eravacycline + ampicillin/sulbactam, with 7 of those patients also receiving inhaled colistin (Table 2). In total, 17 (68%) patients achieved clinical resolution of CRAB pneumonia. Post-treatment sputum cultures were collected in 18 patients, of which 13 (72%) achieved microbiological resolution. One patient received &gt; 14 days of therapy and no patients re-initiated therapy within 48 hours of eravacycline completion. Table 1:Baseline CharacteristicsTable 2:Study Outcomes

Conclusion
In this small case series, eravacycline showed favorable clinical outcomes in patients with CRAB pneumonia. In light of limited treatment options, this agent can be considered for CRAB pneumonia salvage therapy.

Disclosures
All Authors: No reported disclosures.
658. Evaluation of Effectiveness of Cefmetazole vs Meropenem for Invasive Urinary Tract Infections Caused by ESBL-Producing Escherichia coli: A Prospective Multicenter Observational Study
Authors: Hayakawa Kayoko , Uemura Kohei , Matsumura Yasufumi , Sakurai Aki , Tanizaki Ryutaro , Shinohara Koh , Hashimoto Takehiro , Kato Hideaki , Matono Takashi , Hase Ryota , Mawatari Momoko , Hara Hiroshi , Hamada Yukihiro , Saito Sho , Doi Yohei 
Published: December 2022

Abstract

Background
ESBL-producing E. coli (ESBLEC) continues to increase worldwide. For the infection due to ESBLEC, no antimicrobial agent has clearly demonstrated therapeutic effectiveness comparable to that of carbapenem. Overuse of carbapenems may lead to an increase in carbapenem-resistant bacteria. Cefmetazole (CMZ) is active against ESBLEC, however, there are limited multicenter studies on the effectiveness of CMZ, an important carbapenem-sparing therapy for the treatment of ESBLEC.

Methods
This prospective, observational study included patients hospitalized for invasive urinary tract infection (iUTI) due to ESBLEC between March 2020 and November 2021 at 10 centers in Japan, with either CMZ or meropenem (MEM) initiated within 96 hours of culture submission as definitive therapy, and used for at least 4 days. The diagnosis of iUTI was made in patients with a fever of ≥37.5°C, symptom of pyelonephritis such as back pain, pyuria, and ESBLEC detected in urine (≥10^4 CFU/mL). Outcomes included clinical effectiveness (resolution of all clinical symptoms or improvement to pre-infection status) between day 4 to 6 of treatment (early) and between the final day of treatment and 2 days later (late), microbiological effectiveness (reduction to ≤10^3 CFU/ml) between day 4 to 6, and mortality. Outcomes were adjusted for the inverse probability of propensity scores (PS) for receiving CMZ or MEM treatment.

Results
Seventy-seven patients in the CMZ group and 46 in the MEM group were included. In univariate analysis, the CMZ group was older than the MEM group, although the MEM group had higher qSOFA, CRP, more frequent medical device use and concurrent bacteremia at the start of study drugs than the CMZ group (Table). Univariate analysis showed no difference in clinical effectiveness, and 30-day mortality was higher in the MEM group. In all cases with available data (CMZ: n=57, MEM: n=22), both drugs were microbiologically effective. After PS adjustment, clinical effectiveness did not differ between the two groups. The risk of 30-day mortality was lower in CMZ group, whereas the risk of recurrence was similar in both groups.

Conclusion
CMZ is as effective as MEM for the treatment of iUTI, suggesting that it is a promising carbapenem-sparing therapy.

Disclosures
Sho Saito, MD, PhD, DAIICHI SANKYO: Grant/Research Support|EVEC: Grant/Research Support|EVEC: Patents obtained through collaborative research|SHIONOGI: Grant/Research Support|Takeda: Advisor/Consultant.
674. Successful Management of ESBL Infections in Physician Outpatient Infusion Centers (POICs)
Authors: Nathan Ramesh V , Metzger Brian S , Bernett Jorge R , Adams John S , Hengel Richard L , Bhattacharyya Rishi , Schroeder Claudia P , Couch Kimberly A , Van Anglen Lucinda J 
Published: December 2022

Abstract

Background
Infections with extended-spectrum β-lactamase (ESBL)-producing pathogens present treatment challenges with higher costs of care. Hospitalized patients (pts) with ESBL infections often require outpatient antimicrobial therapy (OPAT) following discharge. An Infectious Disease (ID) physician can facilitate optimal management in both the inpatient and outpatient setting, particularly when a POIC is an option. The increase of ESBL incidence led us to evaluate management and outcomes of genitourinary (GU) and intra-abdominal infections (IAI), the top two ESBL diagnoses treated in POICs.

Methods
Records were queried for pts hospitalized with ESBL infection and discharged to a POIC between 2019 and 2020. Primary outcome was completion of OPAT. Non-successful completion was defined as premature discontinuation of OPAT including hospital readmission. Adverse events (AEs) and re-treatment within 30 days were captured.

Results
A total of 112 pts (mean age: 59±17 years, 50% female) from 14 POICs were identified (93 GU, 19 IAI). Of these, 51% had their first ESBL infection and 52% were community-acquired prior to hospitalization. A total of 38% presented with concomitant bacteremia. ESBL E. coli was the predominant Gram-negative pathogen in both infection types (Table 1). Mean hospital LOS was 6±4 days (5±2 days GU, 11±6 days IAI) followed by 13±9 days of OPAT (12±7 days GU, 16±11 days IAI). Carbapenems were most frequently used as treatment (89% ertapenem, 7% meropenem). Overall, 106 pts (95%) successfully completed OPAT. Six pts (5%) discontinued due to hospital readmission. AEs were reported in 15 pts (13%), the majority of which were mild. Re-treatment in the POIC within 30 days post OPAT completion occurred in 6 GU pts. None were lost to follow-up. Table 1 summarizes primary outcome by clinical characteristics. Both GU and IAI pts had 95% successful OPAT completion. Table 1.Successful and non-successful completion of OPAT in patients with ESBL infections

Conclusion
Outpatient treatment of ESBL infections in POICs post-hospitalization showed high completion rates with low occurrence of readmissions and re-treatments. Consistent with a rise in ESBL infections, our incidence of community-acquired ESBL infections prior to hospitalization were high at 52%. Once ESBL infections were identified in the hospital, the ID physicians with a POIC rapidly facilitated discharge to OPAT.

Disclosures
Ramesh V. Nathan, MD, FIDSA, Eli Lilly & Co.: Grant/Research Support Brian S. Metzger, MD, MPH, AbbVie: Advisor/Consultant|Cumberland: Advisor/Consultant Lucinda J. Van Anglen, PharmD, Merck & Co.: Grant/Research Support|Paratek: Grant/Research Support.
676. Synergistic Bacteriostatic and Bactericidal Activity of Fosfomycin Plus Trimethoprim-Sulfamethoxazole Combination Against Carbapenem-Resistant Enterobacteriales, Multidrug-Resistant P. aeruginosa, Carbapenem-Colistin-Resistant A. baumannii, MRSA, and Enterococcus spp.
Authors: Pace John L 
Published: December 2022

Abstract

Background
Fosfomycin (F) inhibits the first committed step of peptidoglycan biosynthesis catalyzed by the MurA enzyme which uses phosphoenolpyruvate as a substrate. Trimethoprim and sulfamethoxazole (TS) inhibit successive steps in folate biosynthesis and are commonly used as a fixed combination (co-trimoxazole). In this study we explored the combination (FTS) of F with TS in several gram-negative and gram-positive bacteria of increasing concern.

Methods
We used the synergy-checkerboard variant of the agar minimal inhibitory concentration (MIC) assay with Mueller-Hinton Agar (glucose-6-phosphate supplemented; CLSI) against a selection of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus spp. clinical isolates to characterize an FTS combination. Component antibiotics, F and TS, and a variety of other antibacterial comparators were evaluated by agar method or broth microdilution. Bactericidal assays of FTS were conducted in broth.

Results
Antibacterial synergy with FTS was exhibited against all E. coli (20/20) at antibacterial concentrations below the individual clinical breakpoints for F and TS. Against K. pneumoniae isolates, all (12/12) that were resistant to F, and many (10/13) resistant to both F and TS, were susceptible to FTS. All P. aeruginosa isolates (18/18) were dually resistant to F and TS. Extrapolating breakpoints for Enterobacteriales, clinically-relevant synergy of FTS was exerted against 11/18 isolates, and susceptibility was achievable for one component in combination against 7/18 isolates. Against A. baumannii, susceptibility values below extrapolated breakpoints for FTS were achieved for most isolates (17/19), and for a few (2/19), susceptibility was observed for one component in combination. FTS was active against all MRSA and Enterococcus spp. regardless of F or TS susceptibility.

Conclusion
The unique synergistic and bactericidal activity of the FTS combination was not impacted by resistance of the tested species to any other antibacterial agent including carbapenem-resistant Enterobacteriales, P. aeruginosa, carbapenem-colistin-resistant A. baumannii, MRSA, or Enterococcus spp.

Disclosures
John L. Pace, PhD, FleurirABX, LLC: Board Member|FleurirABX, LLC: Inventor of company patents|FleurirABX, LLC: Ownership Interest.
895. Comparing Antibiotic Durations in Acute Appendicitis After Source Control
Authors: Alberts John L , Torney Nicholas , Nichols Cynthia 
Published: December 2022

Abstract

Background
Community-acquired acute appendicitis is a common intra-abdominal infection that often requires surgical intervention and antibiotics. Despite guideline recommendations for narrow-spectrum regimens and shorter durations, broad-spectrum agents are frequently used for extended durations in community-acquired cases of appendicitis.

Methods
We conducted a retrospective chart review of 95 adult patients admitted to a community hospital in rural northern Michigan with acute appendicitis with or without perforation who underwent source control and received at least 72 hours of antibiotics after source control. Patients were assigned to a short course group (4-7 days) or a long course group (≥ 8 days). Total antibiotics is the sum of the inpatient duration and outpatient duration after source control. The primary outcome was hospital readmission within 30 days of discharge due to complications related to appendectomy or antibiotic failure. Secondary outcomes included hospital mortality, surgical site infection within 30 days, additional source control needed during initial stay, number of patients receiving piperacillin-tazobactam, and proportion of patients who received guideline concordant duration of therapy.
Baseline characteristics between treatment groups

Results
The primary outcome was met in 1/32 patients (3.13%) from the 4–7 day group and 4/63patients (6.35%) in the ≥8-day group (P = 0.66). There were no cases of mortality. Surgical site infection occurred in 1/63 patients (1.6%) in the ≥8-day group (P = 1). Additional source control was needed in 1/32 patients (3.13%) from the 4-7 day group and 3/63 patients (4.76%) in the ≥ 8 day group (P = 1). Piperacillin-tazobactam was prescribed to 21/32 patients (65.6%) in the 4-7-day group and 42/63 patients (67%) in the ≥ 8day group (P =0.91) Piperacillin-tazobactam was appropriately used in 1/21 patient (4.76%) in the 4-7 day group and 6/42 patients (9.5%) in the ≥ 8 day group (P = 0.41).
Outcomes
Results of the primary outcome and the piperacillin/tazobactam based secondary outcomes
Treatment Duration Between Groups
Comparison of total treatment duration between groups with inpatient and outpatient averages
Total Antibiotic Duration Frequency
Distribution of total antibiotic days of patients analyzed in this study

Conclusion
In patients with community-acquired acute appendicitis with or without perforation who had undergone adequate source control, outcomes were similar between a 4-7 day course of antibiotics and ≥ 8 day course. Piperacillin-tazobactam was often prescribed for community-acquired appendicitis cases despite guideline recommendations.

Disclosures
All Authors: No reported disclosures.
896. Cost-Avoidance Associated with Active Stewardship of Remdesivir
Authors: Dyer April , Locklear Eric , Okoye Obiefuna , Ashley Elizabeth Dodds 
Published: December 2022

Abstract

Background
The COVID pandemic shifted antimicrobial stewardship resources at community hospitals. One reason for this shift was new COVID treatments, the first of which was remdesivir, which received initial emergency use authorization (EUA) for the treatment of COVID-19 in May 2020. The UNC Health Southeastern (UNC SEH) pharmacy director stewarded remdesivir by reviewing patients to ensure they met emergency use authorization (EUA) and guideline-based appropriateness criteria. The infectious diseases physician resolved any disputes regarding patient candidacy for remdesivir. The goal of remdesivir stewardship was to optimize care; however, the shift in workflow presented an unrecognized opportunity for stewards to reduce remdesivir costs.

Methods
The percentage of COVID patient admissions receiving remdesivir at UNC SEH for calendar years 2020 and 2021 was benchmarked against 32 community hospitals in the Duke Antimicrobial Stewardship Outreach Network (DASON) (Figure 1). UNC SEH purchasing data were used to calculate remdesivir expenditures for 2020 and 2021. Next, the anticipated cost if the hospital had prescribed remdesivir to the same percentage of admissions as the DASON mean was calculated. The difference was calculated to determine the cost avoidance achieved by having below average use of remdesivir (Table 1).

Results
At UNC SEH, 28.1% of COVID admissions received remdesivir in 2020 and annual remdesivir expenditures were $693,680. In 2021, 47.45% of COVID-19 admissions received remdesivir and drug expenditures were $1,248,000. The DASON mean % of COVID admissions receiving remdesivir in 2020 was 44.08% and 60.07% in 2021. A total cost avoidance of $726,407 was calculated based on the hospital’s below-benchmark use of remdesivir (Table 1).

Conclusion
UNC SEH achieved significant cost-savings in 2020 and 2021 due to active remdesivir stewardship. The team created a patient-centered model that focused on using drugs for the right patients and the organization realized cost-savings while ensuring that patients received therapy in accordance with remdesivir EUAs and published guidelines.

Disclosures
All Authors: No reported disclosures.