bluuebunny/crossref_metadata_2025 huggingface dataset:
629. Vancomycin AUC:MIC-Based Dosing is Associated with Significantly Less Acute Kidney Injury in Patients Admitted to a Burn Intensive Care Unit
Authors: Rummel Gregory , Pruskowski Kaitlin A
Published: December 2022

Background

Vancomycin is often used for empiric coverage of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin is well known to cause acute kidney injury (AKI), which can be detrimental to patients in the intensive care unit (ICU) setting. In 2020, the American Society of Health-systems Pharmacists updated their vancomycin dosing guidelines to target an area under the plasma concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC) of 400-600 mg*h/L, a change from targeting a trough concentration of 10-20 mg/L. This suggests that vancomycin toxicity is likely minimized using the AUC:MIC ratio.

Methods

This retrospective cohort study compares the incidence of AKI in patients admitted to the burn ICU dosed to achieve a target to those dosed to achieve an AUC:MIC goal. Incidence of AKI, per the AKIN criteria, was recorded. Known risk factors such as history of hypertension, concomitant furosemide use, pre-existing renal insufficiency, and other concomitant nephrotoxins were considered. All data collected were previously obtained as a part of usual practice.

Results

Two hundred thirty-six subjects who received 317 courses of vancomycin were included. One hundred twenty courses were dosed to achieve an AUC goal, and 197 courses were dosed to achieve a trough goal. In the AUC group, 49 (57.7%) subjects were admitted for burns, 21 (24.7%) were admitted for necrotizing soft tissue infection (NSTI), and 15 (17.7%) were admitted for other reasons. In the trough group, 97 (64.7%) were admitted for burns, 22 (18.7%) for NSTI, and 25 (16.7%) for other reasons. Demographics were similar between the two groups. The incidence of AKI was 10.3% in the AUC group, as compared to 20.3% in the trough group (p=0.0171). Patients in the AUC group received significantly less vancomycin than in the trough group (3524 ± 1551 vs 3145 ± 1491, p=0.0315). Risk factors for AKI were similar between the two groups (55.6% vs 52.8%, p=0.6347), and concomitant nephrotoxin exposure was similar (52.6% vs 42.7%, p=0.0924).

Conclusion

Using AUC:MIC-based dosing was associated with a decreased incidence of AKI than trough-based dosing in patients admitted to the burn ICU.

Disclosures

All Authors: No reported disclosures.
630. A Single-Center 10-Year Analysis of Immunizations in Heart Transplant Recipients
Authors: Snellings Robin , Padakanti Sowmya , Cahuayme-Zuniga Lizbeth
Published: December 2022

Background

Vaccine-preventable diseases pose a risk towards heart transplant recipients on lifelong immunosuppression. Immunization rates are low (30-80%) in solid organ transplants. The aim of this study was to examine the vaccination rates in our hospital’s heart transplant recipients with a goal to expose deficiencies and formulate strategies to increase vaccination in this population.

Methods

This study is a single-center retrospective chart review of patients aged 18 or older who received a heart transplant between January 1, 2012 and March 31, 2022 at our institution in Temple, Texas. We documented vaccination status or seropositivity prior to or after transplant, as recommended by the American Society of Transplantation (AST) for influenza, hepatitis B, hepatitis A, measles, mumps, and rubella (MMR), 23-valent pneumococcal polysaccharide (PPSV23), 13-valent pneumococcal conjugate (PCV13), tetanus, diphtheria, and acellular pertussis (Tdap), varicella, zoster, and COVID-19 immunizations. We evaluated the association with an Infectious Disease (ID) consult. Odds ratios (OR) were calculated with 95% confidence intervals.

Results

72 patients received a heart transplant within the 10-year period. Demographics are noted in table 1. Table 2 presents the immunization status as follows: 48.7% for flu vaccine, 55.5% for Hepatitis B, 47.1% for Hepatitis A, 36.1% for MMR, 67.5% for PPSV23, 67.5% for PCV13, 54.1% for Tdap, 83.3% for Varicella and 13.8% for Zoster, and 53.5% for COVID-19. From 2016, an ID consult was required pre-transplant; 45 patients (62.5%) had an ID consult before transplant. ID consult was associated with increased likelihood of receiving the MMR, PCV13, Tdap, and Zoster vaccines (table 3). Table 1Patient demographics

Table 2 Immunization status in heart transplant recipients

Table 3 Immunization status associated with ID consult

Conclusion

This study reveals the deficiency of vaccinations in our heart transplant patients, but an ID consult was associated with better immunization rates. To further increase compliance, we propose different interventions including close follow-up with ID, addressing vaccine costs, accessibility limitations, cultural hesitancy, and implementation of protocols.

Disclosures

All Authors: No reported disclosures.
634. Implementation of a medical education intervention to improve acceptance of HIV-positive donors for transplant at a tertiary care hospital
Authors: Swaminathan Neeraja , Hemmige Vagish , Czeresnia Jonathan Mamber , Muggia Victoria , Azzi Yorg , Akalin Enver , Raees Harith , Al Anssari Haider
Published: December 2022

Background

The HIV Organ Policy Equity Act (HOPE Act) was enacted in the US on November 21, 2013. HIV patients have a higher waitlist mortality and decreased access to transplant compared to HIV negative controls. The HIV Organ Policy Equity Act (HOPE Act) was a major step towards increasing the donor pool, but utilization of organs through the act has been less than initially anticipated.. Our own institution performed only one HIV D+/R+ transplant in the first four years of the trial despite a significant number of HIV+ patients on the waitlist. TableFigure summarizing perceived barriers and targeted interventions. Rate of HOPE transplants impacted positively by intervention Rate of HOPE transplants impacted positively by intervention

Methods

Monthly multidisciplinary meetings were set up. The agenda included discussing all offers, risks/benefits in a standardized format. Didactic sessions were conducted to address identified barriers to accepting HIV+ organs (Figure 1). HOPE consultants from experienced larger-volume centers were invited as guests.

Results

In the 15 months since this intervention was implemented, there have been 7 HIV D+/R+ transplants including a heart-kidney transplant. While the overall rate of transplant didn't change in a statistically significant way pre and post intervention for patients the rate of HOPE transplants increased significantly (Figure 2).

Conclusion

Making organs from HIV-positive donors available for donation does not mean they will be used. Intensive provider education can improve organ acceptance rates and help fulfill the promise of the HOPE act.

Disclosures

Vagish Hemmige, MD, Merck: Grant/Research Support.
638. Utility of Recombinant Hepatitis B Vaccine in Pre-liver Transplant Candidates
Authors: Rogers Jack , Prasad Pooja , Weinberg Amy , Bynon John S , Machicao Victor I , Nigo Masayuki
Published: December 2022

Background

A recombinant, adjuvanted Hepatitis B (HBV) vaccine (HepB-CpG) was approved by the FDA in 2017. Initial FDA data showed greater immunogenicity than comparable recombinant HBV vaccines. Moreover, it requires only two doses over four weeks instead of three doses over six months, so there is a time advantage to HepB-CpG, which is advantageous in pre-liver transplant candidates, given their limited time before transplantation. The efficacy in this population is unknown, so we explored its efficacy This study aims to explore the efficacy of HepB-CpG in pre-liver transplant candidates, as there is currently no data on this subject.

Methods

This study was a retrospective review of pre-liver transplant candidates greater than 18 years old at Memorial Hermann Hospital in Houston, TX, who received at least two doses of HepB-CpG. Patients were identified from our pre-liver transplant database. Patient characteristics were collected at the time of the first dose. Vaccine efficacy was measured by anti-Hepatitis B surface antibody titers (≥10mIU/mL) at least four weeks after completion of the series. Patients who received only one dose or did not have any post-vaccine titers were excluded from the analysis.

Results

A total of 78 potential eligible patients were identified. After exclusion due to various reasons, a total of 27 patients were eligible for our study. Data are summarized in Table 1. Briefly, our patients were Hispanic dominant (59.3%). The median MELD score was 18, and a significant number of patients (48.1%) had underlying malignancy. The cause of cirrhosis was mainly due to alcoholic and non-alcoholic steatohepatitis (NASH). Only 13 patients (48.1%) showed seroconversion after their second dose of HepB-CpG. Moreover, of the five patients receiving immunosuppressive drugs, only one patient (20%) responded to the vaccine.

Characteristics of Pre-Liver Transplant Candidates Who Had Serological Evaluation after Two Doses of Recombinant Adjuvanted Hepatitis B Vaccine.

Conclusion

Despite administration of HepB-CpG, less than 50% of pre-liver transplant candidates showed seroconversion. Furthermore, only one cirrhotic patient on immunosuppressive drugs responded to the vaccine. Our results illustrate the need for a better strategy to improve immunogenicity among this patient population. Larger studies are warranted to confirm the findings.

Disclosures

Victor I. Machicao, M.D., Gilead Inc: Advisor/Consultant.
640. A Retrospective Assessment of the Effects of Cefiderocol in Patients with Multidrug-resistant Gram-negative Bacterial Infections
Authors: Sajib Monirul I , Go Roderick , Monteforte Melinda
Published: December 2022

Background

Cefiderocol has emerged recently as a new tool for combating multidrug-resistant bacterial infections; however, concerns about its efficacy has approved its FDA approval for the use in person with limited or no treatment options. The aim of our study is to assess the outcomes of patients treated with cefiderocol for such infections.

Methods

Retrospective cohort study which includes all adult patients who received cefiderocol for at least three days from 1 October 2020 to 31 December 2021 at Stony Brook University Hospital. Patients who received multiple courses of cefiderocol during the same hospitalization or are still hospitalized were excluded.

Results

22 patients received cefiderocol and met the inclusion criteria. Average age, Charlson comorbidity index, and length of stay were 63.6 year, 5.4, and 53 days respectively.

6 patients had respiratory tract infections, 3 had bacteremia, 2 had complicated UTI, and 11 had infections in other sites. Bacteria isolates included Pseudomonas aeruginosa (14), Acinetobacter baumannii complex (8), and Stenotrophomonas maltophilia (1).

The 14-day and 28-day all-cause mortality for all patients was 4.5% and 13.6%, respectively. The 14-day and 28-day all-cause mortality for patients with respiratory tract infections was 16.7% and 16.7%, bloodstream infections was 0% and 0%, complicated UTI was 0% and 0% and with infections at other sites was 0% and 15.4%, respectively. These rates are lower compared to CREDIBLE-CR study.

The 28-day all-cause mortality in double gram-negative coverage group (including cefiderocol) was 0% versus 25% in the cefiderocol monotherapy group (p=0.25). The 28-day all-cause mortality in patient group with Pseudomonas aeruginosa was 14.3% vs. with Acinetobacter baumannii complex was 12.5%. Out of 18 isolates, 13 (72.2%) were susceptible to cefidericol, 1 (5.5%) was intermediate, and 4 (22.2%) were resistant. No carbapenemases were detected in any of the 11 tested clinical isolates of Pseudomonas aeruginosa. Treatment failure, defined as requiring change of antibiotic, was 9.1%.

Conclusion

The 14-day and 28-day all-cause mortality for all patients treated with cefiderocol are possibly lower than once thought to be. No significant differences were noted when cefidericol was used as monotherapy versus in combination.

Disclosures

Roderick Go, DO, Aptose Biosciences: Stocks/Bonds|Bristol Meyers Squibb: Stocks/Bonds|Cytodyn Inc.: Stocks/Bonds|Scynexis: Grant/Research Support.
648. Cefiderocol as Rescue Therapy for Pseudomonas aeruginosa and Other Difficult-To-Treat Gram-Negative Infections
Authors: Chou Andrew , Ramsey David J , Trautner Barbara
Published: December 2022

Background

Cefiderocol is a novel siderophore cephalosporin and the only beta-lactam that has demonstrated in vitro activity against metallo-beta-lactamase producing organisms. The open-label phase 3 study CREDIBLE-CR unexpectedly found a higher mortality rate in the cefiderocol group compared to best available therapy. Post-approval, real-world clinical data of cefiderocol use are limited. We sought to describe nationwide, real-world outcomes, clinical characteristics, and microbiological characteristics of infections treated with cefiderocol.

Cefiderocol use since FDA approval (Nov 2019)

Methods

The Department of Veterans Affairs (VA) Corporate Data Warehouse was queried to identify any patient prescribed cefiderocol at any of the 171 VA medical centers from date of FDA approval in 11/2019 until 11/2021. Clinical, pharmacy, demographics, and microbiology data were computationally extracted, supplemented by manual review. All patient charts were manually reviewed to determine the indication for cefiderocol and clinical outcomes.

Results

Twenty-five patients have been prescribed cefiderocol; two received only one dose, and one patient had incomplete records. Prior to 2021 there were four prescription, and since 2021 there have been 21 prescriptions. Of the 22 evaluated patients, their median age was 70 years and 82% were receiving care in the ICU. Infecting organisms (n=25) were Pseudomonas aeruginosa 63%, A. baumannii 18.5%, and Enterobacterales 18.5%. Cefiderocol susceptibility was tested on 17 isolates, of which 15 (88.2%) were susceptible. The two non-susceptible organisms were A. baumannii and P. aeruginosa. The susceptibilities of the 25 strains overall were as follows: carbapenems (13.8%), ceftazidime/avibactam (4 of 12, or 33.3%), and ceftolozane/tazobactam (7 of 15, or 46.7%). The most common infectious syndromes were pulmonary and central line-related infections, occurring in 38.5% and 23.1%, respectively. The 28-day mortality rate was 31.8%, 28-day clinical failure rate was 45.5%, and the 28-day microbiological failure rate was 31.8%.

Conclusion

Patients prescribed cefiderocol in this series had severe infections with high rates of mortality and few alternative antibiotic options. Susceptibility to cefiderocol was higher than for other antibiotics tested.

Disclosures

Barbara Trautner, MD, PhD, Genetech: Advisor/Consultant.
649. Cefiderocol in Treating Patients Confirmed with Gram-negative Infections in US Hospital During Jan 2020 - Jun 2021
Authors: Cai Bin , Zhou Yun , Cooper Andrew
Published: December 2022

Background

Cefiderocol (CFDC) has a broad activity against Gram-negative (GN) pathogens. This study describes the usage of CFDC in US hospitals in patients with microbiology data during the initial phase of commercialization.

Methods

This retrospective study included patients with laboratory-confirmed GN infections in US hospitals treated with CFDC consecutively for ≥3 days between March 2020 to June 2021, as captured by Premier Healthcare data. This study describes the clinical characteristics, microbiology profile, CFDC usage, and post-CFDC initiation 14-day and 28-day in-hospital all-cause mortality (IH-ACM). Index culture was defined as the last day that culture sample(s) was taken before CFDC initiation or the first day the culture sample(s) was taken after CFDC initiation if no microbiology data before CFDC use was available. Index pathogens were all pathogens identified from the index culture(s). The index culture site was where the index culture was taken.

Results

A total 187 in-patients received ≥3 days CFDC and had ≥1 microbiological result(s). The clinical characteristics of the patients and index culture results are provided in Table 1 and Table 2. About 60% of patients had at least one positive respiratory culture. The most frequent pathogens from the index culture were Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Acinetobacter baumannii. Nearly 75% of patients had one index pathogen, and 91% with one culture site. Almost 30% of patients had either one pathogen identified in multiple culture sites, or multiple pathogens from ≥1 culture site. Crude 28-day IH-ACM for patients with any A. baumannii was 8.3% (95%CI: 0% -19.4%), any P. aeruginosa was 17.3% (95%CI: 9.9-24.8%), any S. maltophilia was 18.4%, (95%CI: 6.1%-44.0%) and any K. pneumoniae was 26.1% (95%CI: 8.1%-44.0%). Crude 28-day IH-ACM for patients with positive respiratory culture was five times higher in COVID patients than non-COVID patients.

Conclusion

During the initial phase of CFDC availability, the most frequent pathogens treated using CFDC were non-fermenters, and the most frequent culture site was respiratory. IH-ACM appears to be affected by infection characteristics, especially COVID-19 status.

Disclosures

Bin Cai, MD, PhD, Shionogi: Shionogi employee Yun Zhou, MS, Shionogi: Employee of CRO hired by Shionogi Andrew Cooper, PhD, Shionogi: Shionogi employee.
650. Cefiderocol use in burn patients admitted to an intensive care unit
Authors: Pruskowski Kaitlin A , Kiley John L , Cancio Leopoldo C
Published: December 2022

Background

Cefiderocol is a novel cephalosporin that binds to ferric acid and is moved across the outer membrane of Gram-negative bacilli via iron transport. Once through the outer membrane, cefiderocol is able to exert typical cephalosporin activity. Because of its ‘Trojan horse’-like mechanism of action, cefiderocol is able to elude typical bacterial resistance mechanisms and has activity against multidrug-resistant organisms (MDROs), including Acinetobacter spp. and Pseudomonas spp. While cefiderocol is considered to be relatively safe, it does have the potential to predispose to secondary infection with Clostridioides difficile. We present a case series where cefiderocol was used to treat infections caused by MDROs in burn patients admitted to our burn intensive care unit (BICU).

Methods

A clinical review of patients admitted to the BICU who received cefiderocol between September 2019 and April 2022 was performed.

Results

Five patients received 6 courses of cefiderocol. Three patients (60%) had flame burns, one patient (20%) had a scald burn, and one patient (20%) had blast injury. The median burn size was 47% TBSA (IQR 31, 60 days). The median time from injury to cefiderocol initiation was 73.5 days (IQR 49.5, 108). The median duration of cefiderocol therapy was 7 days (IQR 7, 16). The most common indications for cefiderocol treatment were pneumonia (33.3%) and bacteremia (33.3%), followed by wound infection (16.7%), and discitis/osteomyelitis (16.7%). Organisms isolated included Escherichia coli (n=2), Enterobacter cloacae (n=1), Acinetobacter baumannii (n=1), and Pseudomonas aeruginosa (n=2). All isolates were carbapenem resistant, and only one isolate was susceptible to amikacin (Acinetobacter baumannii). The 2 E. coli isolates carried a New Delhi metallo-beta lactamase. Two thirds of patients (n=4) achieved a clinical cure with cefiderocol treatment. Three of the 5 patients (60%) died during their hospital stay.

All patients received appropriate doses of cefiderocol based on the current prescribing recommendations. No patients developed infection with C. difficile as a result of cefiderocol treatment.

Conclusion

Cefiderocol is a cephalosporin with novel mechanism of action that can be used to treat MDROs in burn patients, with no secondary C. difficile infections observed.

Disclosures

All Authors: No reported disclosures.
654. Clinical efficacy and safety of high dose Ampicillin sulbactam among patients with CRAB infections: A case series
Authors: Warrier Anup R , Sneha R , Wilson Arun , Prakash Shilpa
Published: December 2022

Background

CRAB continues to threaten the healthcare facilities in developing nations and is one among the commonest causes of hospital acquired infections in our hospital. In December 2021, the IDSA published the AMR guidance 2.0, that stated Ampicillin- sulbactam as the first choice for treating CRAB infections. We review the clinical outcomes with adherence to this guideline in our setting.

Methods

A descriptive study from India (January 2022 to April 2022), of in-patients who have received ampicillin sulbactam monotherapy or combination for CRAB infections. A standard treatment guideline for the identification and management of CRAB infections was introduced to the clinicians based on the AMR guidance 2.0 of IDSA. CRAB infections were classified as mild to severe based on clinical and radiological parameters. We collected the data on patients who were started on ampicillin sulbactam, given in a high dose (27g per day or renally adjusted) as a 4-hour infusion either alone or as combination with other antibiotics for the indication of CRAB infections.

Results

Ampicillin-Sulbactam was started for 12 patients with CRAB infection. 2 of these patients were discharged while on treatment and hence, excluded. 6 out of the 10 patients were being treated for CRAB associated hospital acquired pneumonia, whereas the other indications included urinary tract infection, post neurosurgical meningitis and skin and soft tissue infections. Susceptibility testing to Ampicillin-Sulbactum was not possible in our setting. All the patients survived from 14 days of starting the therapy and 9 out of 10 patients improved clinically (in terms of defervescence or symptomatic relief) by day 7. No adverse effects were noted either in clinical symptoms or Laboratory parameters during the course of treatment.

Conclusion

High dose Ampicillin-Sulbactum is effective and safe for CRAB infections with varying clinical syndromes and severity. All patients in this case series were treated with Colistin sparing regimens when combination therapy was required.

Disclosures

All Authors: No reported disclosures.
661. In vitro Activity of Omadacycline and Comparator Antibiotics against Clostridioides difficile
Authors: Skinner Andrew M , Petrella Laurica A , Cheknis Adam K , Johnson Stuart
Published: December 2022

Background

Omadacycline was approved for the treatment of community acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in 2018. Previous studies demonstrate that omadacycline has in vitro activity against Clostridioides difficile. We determined the in vitro activity of omadacycline and of comparator antimicrobials for the approved indications, CABP and ABSSSI, towards a contemporary and clinically relevant collection of C. difficile isolates.

Methods

Antimicrobial agar dilution was performed on 200 clinical C. difficile isolates collected from 2014 – 2021. Isolates were selected based on the most prevalent restriction endonuclease analysis (REA) groups locally and nationally. Omadacycline was compared to 8 standard of care antimicrobials for CABP and ABSSSI: amoxicillin-clavulanate, azithromycin, ceftriaxone, clindamycin, doxycycline, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole.

Results

Omadacycline demonstrated in vitro activity against all C. difficile isolates tested. The geometric mean MIC of omadacycline was 0.07 μg/ml and the MIC50 and MIC90 were 0.0625 μg/ml and 0.125 μg/ml, respectively. Among the comparator antibiotics, 52% of isolates were resistant to ceftriaxone and 37% of isolates were resistant to clindamycin. The majority of REA group BI isolates were resistant to clindamycin (77.7%, 28/36) and the clindamycin geometric mean MICs were higher for group BI compared to all other REA group strains (32 µg/ml and 5.33 µg/ml, respectively, p < 0.005). REA group BI also had elevated azithromycin and moxifloxacin geometric MICs (335.2 and 17.3 µg/ml, respectively). REA group DH isolates had higher trimethoprim-sulfamethoxazole geometric MICs compared to all other REA group strains (17.28 µg/ml and 8.14 µg/ml, respectively p >0.001). Nearly half of REA group BK isolates (47%) had MICs ≥2 µg/ml which did not correspond to elevated omadacycline MICs for the same isolates.

Conclusion

Omadacycline demonstrated consistently low MICs against C. difficile when compared to approved antimicrobials for CABP and ABSSI which varied in activity among particular C. difficile strains. Omadacycline may reduce the risk of developing a C. difficile infection and requires further study.

Disclosures

Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant.
672. Report of a Multi-species Outbreak of VIM-producing Carbapenem-resistant Organisms in a Burn Unit and Subsequent Experience Using Novel β-lactam Antibiotics for Treatment
Authors: Freiberg Jeffrey , Tao Lili , Nelson George E , Talbot Thomas R , Humphries Romney
Published: December 2022

Background

The incidence of carbapenem-resistant organisms (CROs) has increased over the past 3 decades. Carbapenem-resistance due to metallo-β-lactamases (MBLs) such as the Verona integron-encoded metallo-β-lactamase (VIM) are particularly problematic due to the limited treatment options. We describe a multi-species outbreak of VIM-producing CROs (VIM CROs) in a tertiary care hospital along with our experience using novel β-lactam antibiotics for treatment.

Methods

We performed a retrospective chart review after a cluster of patients in the burn unit of a tertiary care hospital were found to have infections with VIM CROs. Electronic medical records for all patients with a VIM CRO isolated between November 2021 and March 2022 were reviewed. Data regarding patient characteristics, antimicrobial use, culture results, antimicrobial susceptibility testing, and clinical outcomes were recorded for each patient.

Results

8 patients were found to have VIM-mediated CRO burn wound infections, 5 of whom were also bacteremic with a VIM CRO. A VIM gene was identified in 5 different species (Pseudomonas aeruginosa and 4 Enterobacterales). None of the patients received carbapenems prior to isolation of a CRO. Among the 5 patients treated with cefiderocol, 2 had cefiderocol-resistant VIM CROs isolated 10-20 days after starting cefiderocol. 3 patients received the combination of ceftazidime/avibactam and aztreonam, and all had subsequent clearing of their CRO infection on follow-up cultures taken from the same site. Only one of the 8 patients died within 30 days of initial CRO isolation, after developing a subsequent fungal infection. The median Pitt bacteremia score at the time of initial CRO isolation was 1 (range 0-4) in the 7 patients who survived versus a score of 6 in the patient who died.

Conclusion

MBLs such as VIM have the potential for multi-species spread throughout hospital units even in the absence of carbapenem selection pressure. Although over 60% of the patients in this study had bacteremia and cefiderocol-resistance developed in 40% of the patients treated with cefiderocol, mortality was fortunately low in this group. While newer β-lactam antibiotics remain an exciting addition to our armamentarium, we must remain diligent in monitoring for rapid development of resistance.

Disclosures

Thomas R. Talbot, III, MD, MPH, OmniSolve: Board Member Romney Humphries, PhD, D(ABMM), M(ASCP), Accelerate: Advisor/Consultant|Accelerate: Stocks/Bonds|bioMerieux: Advisor/Consultant|IHMA: Advisor/Consultant|Pattern: Advisor/Consultant|Qiagen: Advisor/Consultant|QPex: Advisor/Consultant|Roche: Advisor/Consultant|Specific Diagnostics: Advisor/Consultant|Specific Diagnostics: Stocks/Bonds|ThermoFisher: Advisor/Consultant|Torus: Advisor/Consultant.
678. Title: Treatment Outcomes with Carbapenems vs. Non-Carbapenem Beta-Lactams in Infections with Carbapenem-Discordant Enterobacter cloacae Complex
Authors: Spence Matthew , Mason Matt , Wilson Nicole , Liesman Rachael
Published: December 2022

Background

Carbapenem-discordant Enterobacter cloacae complex (CDECC) isolates are defined as ertapenem non-susceptible and meropenem susceptible drug phenotype. The optimal treatment of these infections is unknown. In 2021, the Infectious Diseases Society of America released guidance recommending extended infusion meropenem as the preferred treatment option. Newer agents, including ceftazidime-avibactam, may be effective but comparative data is lacking. Evaluation of treatment outcomes for use in infections with CDECC is necessary to establish optimal therapy.

Methods

This single center, retrospective, cohort study was conducted at The University of Kansas Hospital from January 2016 to June 2021. Individuals at least 18 years of age with non-urinary culture positive for CDECC that were treated with either meropenem (MEM) or a non-carbapenem beta-lactam (NCBL) were included. Individuals with polymicrobial infections, infections from a urinary source, or death within 72 hours of admission were excluded. The primary outcome was clinical failure, which was a composite endpoint. Secondary outcomes included individual components of the primary outcome.

Results

There were 29 unique episodes of monomicrobial, carbapenem-discordant Enterobacter cloacae complex infections during the study period. The primary outcome was met in 6 patients receiving a NCBL and 6 patients receiving MEM, respectively (67% vs. 30%, p=0.11). A total of 8 patients died within 30 days, 4 in the MEM group and 4 in the NCBL group (20% vs. 44%, p = 0.21). Univariate logistic regression analysis demonstrated a significant increase in need to modify antibiotic therapy in the NCBL group (OR 15.2, 95% CI, 1.37-168; p=0.02), with a trend towards increased risk for in-hospital 30-day mortality (OR, 3.2; 95% CI, 0.58-17.72; p = 0.18).

Conclusion

There was no difference in clinical failure rates between the MEM and NCBL treatment groups. However, treatment with NCBLs was associated with a trend towards increased in-hospital mortality and need for antibiotic modifications due to clinical decompensation. Larger studies are needed to assess treatment outcomes in carbapenem-discordant Enterobacter cloacae complex infections to define optimal antibiotic therapy.

Disclosures

All Authors: No reported disclosures.
679. Traditional vs. Alternative Agents in Patients with Lower Respiratory Tract Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa Susceptible to Traditional Agents
Authors: Holger Dana J , Lagnf Abdalhamid M , Belza Ana Christine , Alosaimy Sara , Rebold Nicholas S , Morrisette Taylor , Kunz Coyne Ashlan J , Ghali Amer El , Veve Michael P , Rybak Michael J
Published: December 2022

Background

Comparative effectiveness studies to guide treatment decisions for infections caused by carbapenem-resistant P. aeruginosa (CRPA) susceptible to traditional agents (non-carbapenem β-lactams and fluoroquinolones) are unavailable. This study aims to compare clinical outcomes between patients treated with traditional and alternative treatment regimens for lower respiratory tract infection (LRTI) caused by CRPA that remain susceptible to traditional agents.

Methods

Multi-center, retrospective cohort from January 2016 to December 2019. We included adults with CRPA (resistant to ≥ 1 carbapenem; meropenem or imipenem) that were susceptible to ≥1 traditional agent (piperacillin-tazobactam, cefepime, ceftazidime, ciprofloxacin, or aztreonam) by CLSI breakpoints isolated from an LRTI sample. All other antibiotics were considered alternative agents. We excluded patients with known colonization, cystic fibrosis, or who expired ≤24 hours after antibiotic receipt. Primary outcome was 30-day mortality and secondary outcomes included 30-day readmission and 30-day recurrence.

Results

In total, 87 patients, ‘traditional’ treatment (n=53) and ‘alternative’ treatment (n=34), were included from 2 institutions in Detroit, MI, USA: median(IQR) age 59(20) years, 64.4% male, and 59.8% African American. Median(IQR) APACHE II and Charlson Comorbidity index scores were 24(10) and 4(5), respectively. Most patients received traditional therapy (n=53), most commonly with cefepime (60.4%) or piperacillin-tazobactam (41.5%). While 34(39.0%) were treated with alternative agents, most commonly ceftolozane-tazobactam (64.7%) or an aminoglycoside (29.4%) alone or in combination. Thirty-day mortality was not significantly different between traditional and alternative therapy groups (22.6% and 11.8%), respectively. There was no significant difference between 30-day recurrence (17.0% and 20.6%) or 30-day readmission (22.6% and 17.6%) between groups.

Conclusion

Clinical outcomes did not differ significantly between patients receiving traditional vs. alternative agents for LRTI caused by CRPA susceptible to traditional agents. Traditional agents may be considered for these infections. Further comparative studies are needed to guide treatment decisions for CRPA.

Disclosures

All Authors: No reported disclosures.
891. Challenging the Dogma of Beta-Lactam Allergies: Impact of an Antimicrobial Stewardship Program
Authors: Holzworth Abriana , Blum Sharon , Bosco Michael , Baalbaki Nadeem , Davenport Lilia , Munoz-Gomez Sigridh , Okpara Chinyere
Published: December 2022

Background

Penicillin allergies are reported in approximately 10% of patients in the US but ∼90% of these allergies can be de-labeled. Consequences of inappropriate allergy labeling leads to use of alternative agents associated with increased adverse events and resistance rates, leading to worse outcomes. Though all beta-lactam agents share the core beta-lactam ring, the R1 side chain has been identified as the focus of cross-reactivity. Agents that do not share the same or similar R1 side chain are likely to have negligible risk of hypersensitivity reactions. The purpose of this study was to assess the incidence of hypersensitivity reactions in patients with a documented beta-lactam allergy that received a beta-lactam agent with a different side chain based on recommendation by an antimicrobial stewardship clinical pharmacist.

Methods

This was a retrospective, single-center, observational study of patients admitted to NYU Langone Hospital – Long Island from October 2019 to February 2022. Data was collected by review of the electronic medical record and descriptive statistics were generated as appropriate. The primary outcome was the proportion of patients that experienced a hypersensitivity reaction to a beta-lactam agent with a different side chain. Secondary outcomes included impact of antimicrobial stewardship intervention by clinical pharmacists, avoidance of alternative antibiotics, and cost comparison between agents requested and recommended.

Results

A total of 181 patients were included in the final analysis, including 37 patients with a history of anaphylaxis. No patients with a documented beta-lactam allergy experienced a hypersensitivity reaction upon receiving a beta-lactam agent with a different side chain. Within the cost comparison, meropenem accounted for 45.6% and 75.9% of the total minimum and maximum wholesale costs of requested agents, respectively.

Conclusion

The results of this study suggest that receipt of a beta-lactam agent with a different side chain is safe in patients with a history of beta-lactam allergy, including anaphylaxis history, and supports 'in the moment' antimicrobial stewardship intervention to ensure patients receive optimal therapy when access to in-depth allergy history or detailed patient interview is not feasible.

Disclosures

All Authors: No reported disclosures.
892. Clinical Impact of Early Antifungal De-escalation (≤ 2 days) based on Rapid Species Identification in Patients with Azole-susceptible Candidemia
Authors: Lee Sara , Mazur Shawn , Mazur Shawn , Kodiyanplakkal Rosy Priya , Theodore Deborah , Kubin Christine J
Published: December 2022

Background

Echinocandins are first-line therapy of candidemia with an option to de-escalate (DE) to oral azoles based on clinical response and susceptibilities. There are no universally accepted DE criteria but rapid diagnostic testing (RDT) allows for earlier Candida sp. identification. The objective of this study was to compare outcomes between early DE (≤ 2 days) and late DE ( > 2 days) using RDT as an antifungal stewardship strategy.

Methods

This was a retrospective study in adults with candidemia caused by C. albicans, C. tropicalis, and C. parapsilosis from 2017-2021. Patients with neutropenia or deep-seated/uncontrolled source were excluded. Primary outcome was 30-day global response (clinical and microbiological success). Secondary outcomes included clinical and microbiologic success, length of stay after candidemia, development of resistance, infection recurrence, and mortality. Comparisons were performed using Chi-squared or Fischer’s exact test for categorical variables and Student’s t test or Mann-Whitney U for continuous variables. A multivariable logistic regression model was constructed to identify independent factors for global response using DE strategy, ICU status, and considering all variables with a p-value < 0.1 on univariate analysis.

Results

87 patients were included, 34 (39%) in early DE group and 53 (61%) in late DE group. Groups were well matched except early DE patients were less likely to be in the ICU at time of candidemia (18% vs 38%; p=0.079). C. albicans was the most common Candida sp. (54%) and a vascular catheter was the most common source (45%). Overall global response was 93% with an in-hospital mortality of 8%. At the time of DE, 45% were considered hemodynamically unstable. No difference in global response between early and late DE was identified (94% vs 96%, p=1.0). On multivariable analysis, no independent predictors were identified and late DE was not associated with improved global response [OR 0.82 (95% CI 0.08, 8.24)]. No differences were identified in secondary outcomes.

Conclusion

There were no differences in outcomes between early and late DE in the treatment of azole-susceptible candidemia. Early DE within 2 days based on rapid species identification should be considered as an antifungal stewardship strategy based on local susceptibilities.

Disclosures

All Authors: No reported disclosures.
894. Clinical utility of methicillin resistant Staphylococcus aureus (MRSA) nasal PCR to streamline antimicrobial use in the treatment of diabetic foot infection (DFI) with or without osteomyelitis (OM)
Authors: Harb Gaielle , Hopkins Teri L , Yang Linda , Morneau Kathleen , Frei Christopher R , Cadena-Zuluaga Jose , Walter Elizabeth
Published: December 2022

Background

DFI guidelines recommend empiric MRSA-targeted therapy in settings of high prevalence or severe infection; however, they do not provide recommendations for de-escalation. This approach has the potential to increase unnecessary use of broad-spectrum antibiotics; therefore, additional strategies are needed to optimize appropriate antibiotic use. This study evaluates the effect of MRSA nasal PCR testing on MRSA-targeted antibiotic use and clinical outcomes in patients with DFI.

Methods

This was a retrospective quasi-experimental study of patients > 18 years admitted to South Texas VA for DFI, with or without OM, who had an MRSA nasal PCR and culture data. Eligible patients were identified from the Corporate Data Warehouse and reviewed via electronic health record. Patients were allocated into two groups: PRE (5/1/2019-4/30/2020) and POST (12/1/2020-11/30/2021) protocol implementation for de-escalation or avoidance of MRSA-targeted antibiotics. The primary outcome was median (interquartile range [IQR]) days of inpatient MRSA-targeted antibiotic therapy. A Wilcoxon Rank Sum test was used to assess the difference between the groups for the primary outcome. Secondary outcomes included the proportion of patients needing MRSA coverage added back after de-escalation, hospital readmission, length of hospital stay (LOS), patient mortality, and acute kidney injury.

Results

A total of 151 patients were included (83 PRE; 68 POST). Most patients were male (98% PRE; 97% POST) with a median age of 64 (IQR, 56-72) years. There was a significant decrease in MRSA-targeted antibiotic therapy use, from a median of 72 (IQR, 27-120) hours in the PRE group, to 24 (IQR, 12-72) hours in the POST group (p < 0.01). There was also a significant decrease in hospital readmission from 17% in the PRE group to 5% in the POST group (p = 0.02). No significant differences were found for other secondary outcomes.

Conclusion

This study of patients presenting to a VA hospital with DFI identified a statistically significant decrease in median duration of MRSA-targeted antibiotic use post-protocol implementation. This suggests a favorable effect of MRSA nasal PCR for de-escalation or avoidance of MRSA-targeted antibiotics in DFI.

Disclosures

All Authors: No reported disclosures.
899. Evaluation of a Pharmacist-Led Penicillin Allergy Screening Protocol in a Tertiary Care Hospital
Authors: Alzaabi Salma I , El Lababidi Rania M , El Nekidy Wasim S , Hisham Mohamed , Nasef Rama , Salvo Fulvio
Published: December 2022

Background

Although penicillin allergy is commonly reported, less than 1% of the population are truly allergic to penicillin. False penicillin allergy labelling may be associated with suboptimal antibiotic selection, greater costs, and higher prevalence of antibiotic-resistant organisms. The purpose of this study was to evaluate outcomes of implementing a pharmacist-led penicillin-allergy screening protocol on the antibiotic prescribing habits and the appropriateness of selecting first line antimicrobial therapy.

Methods

A retrospective, quasi-experimental study included 97 patients with suspected or confirmed common infections. Data was collected between January 2020 to August 2021 for the pre-protocol implementation group (PPG) and between November 2021 to April 2022 for the post-protocol implementation group (PPI). Adults ( > 18 years) with a documented penicillin allergy were included. Patients with penicillin allergy were identified and interviewed by our Emergency Department (ED) clinical pharmacists using an evidence-based algorithm. Data were analyzed using two-sample Student’s t-test and descriptive statistics.

Results

Fifty-one patients in PPG and 46 in PPI. In the PPG, 60.8% (31/51) had a history of beta-lactam tolerance and 26% (8/31) tolerated at least a penicillin derivative previously. While, twenty-two patients (47.8%) in the PPI tolerated beta-lactams and 50% (11/22) tolerated at least one penicillin derivative. Thirty-eight patients (82.6%) had a documented infection in the PPI and received an antibiotic. The use of Moxifloxacin was significantly lower in the PPI vs the PPG, 0% (0/38) vs 17.6 (9/51) respectively, (P=0.008). However, the use of ciprofloxacin, vancomycin, and aztreonam was lower in the PPI vs the PPG but was not statistically significant (Table 2). Antibiotic therapy appropriateness was higher in the PPI as compared to the PPG, 86.8% (33/38) vs 49% (25/51) respectively, (P=0.0004). In the PPI, documented penicillin allergies were delabeled in 23.9% (11/46) of patients.

Conclusion

We observed higher rates of appropriate first line antibiotic therapy selection post-implementation of the pharmacist led penicillin allergy screening protocol. This could be an effective strategy to optimize antimicrobial therapy in the hospital setting.

Disclosures

All Authors: No reported disclosures.
900. Evaluation of automated blood culture results and subsequent pharmacist intervention on time to targeted therapy in patients with bacteremia
Authors: Spangler Jessica , Gentry Andrew , Bilinskaya Anastasia
Published: December 2022

Background

Bloodstream infections (BSIs) are associated with a high mortality rate and timely administration of empiric broad-spectrum antibiotics is critical. However, prolonged exposure increases the risk of colonization and subsequent infection with resistant bacteria. The use of rapid diagnostics and prospective audit and feedback allows for decreased time to targeted therapy and development of resistance.

Methods

This quasi-experimental study aimed to evaluate changes in time to targeted antibiotic therapy before and after implementation of a real-time pharmacist notification for bacteremic patients. The pre- and post- intervention periods were 9/1/19–12/31/19 and 9/1/21– 12/31/21, respectively. Bacteremic patients that were identified via automated Bruker’s MBT Sepsityper IVD kit reports and admitted for ≥48 hours were included in the study. Patients were excluded if they had ≥ 1 BSI or polymicrobial BSI during hospitalization, treatment of a concurrent infection, or transitioned to hospice. The primary outcome was change in time to targeted antibiotic therapy. Secondary outcomes included change in broad-spectrum antibiotic days of therapy, total duration therapy, hospital length of stay, and in-hospital all-cause mortality.

Results

A total of 132 charts were reviewed, 83 of which were included, with 47 in the pre- and 36 in the post-intervention group. The most common isolates in the study across both groups was E. coli (36.1%), Klebsiella spp. (15.7%), MSSA (15.7%) and MRSA (8.4%). A trend towards decreased time to targeted therapy was seen in the post-intervention group (5.4 hours vs 33.0 hours; p = 0.150). Median duration of anti-MRSA therapy was reduced from 49.4 hours in the pre-intervention group to 27.92 hours in the post-intervention group (p=0.035). There was no significant difference in total duration of therapy, days of anti-pseudomonal therapy, length of stay, or in-hospital all-cause mortality. Of the 22 pharmacist interventions, 18 (81.8%) were accepted. The most common pharmacist intervention was therapy de-escalation (72.7%).

Conclusion

Automated rapid blood culture diagnostic results used in conjunction with real-time notifications to pharmacists, further decreased time to targeted therapy and significantly reduced duration of anti-MRSA therapy.

Disclosures

All Authors: No reported disclosures.