bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &lt; 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 &gt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.