bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1512. Partnering Imipenem/Relebactam (I/R) with Fosfomycin (FOS): Restoring Susceptibility Against Multi-Drug-Resistant Pseudomonas aeruginosa
Authors: Becka Scott A , Zeiser Elise T , Mojica Maria F , Bonomo Robert , Rao Gauri G , Papp-Wallace Krisztina M 
Published: January 2025

Abstract

Background
Pseudomonas aeruginosa (Pae) is a significant pathogen causing up to 10% of hospital-acquired infections. Contributing to Pae’s multidrug-resistant (MDR) phenotype is the inducible Pseudomonas-derived cephalosporinase (PDC), low permeability outer membrane, multiple efflux systems, and loss of porins that yield resistant phenotypes. e.g. loss of OprD yields resistance to imipenem. Thus, the design of novel antibiotics or combination therapies that do not induce expression of blaPDC, are stable to PDC hydrolytic activity, bypass impermeability, and/or are not susceptible to efflux is essential for combating MDR Pae infections. Ceftazidime-avibactam (CZA), and imipenem/cilastatin/relebactam (I/R) were approved by the FDA for the treatment of infections caused by Pae; however, gaps in their efficacy against Pae remain. Previously, Winkler et al. analyzed a group of archived Pae and found that 20% of the isolates were resistant to CZA (PMID 25451057). By combining CZA with fosfomycin (FOS) and targeting multiple cell wall synthetic pathways, susceptibility was restored to most of the CZA resistant MDR Pae (PMID: 31099835). Based upon a similar mechanism of action, we propose that the combination of I/R+FOS will also restore susceptibility to I/R resistant Pae.

Methods
149 isolates of Pae were used in this analysis. Minimum inhibitor concentrations (MICs) of IMI, I/R, and I/R+FOS against 150 P. aeruginosa isolates were determined following CLSI’s approved methods. To interpret the results better, genetic analysis of the resistomes was performed.

Results
The addition of FOS was found to shift the I/R MICs towards the susceptible range (Fig.1A). Moreover, the isolates tested with I/R+FOS possessed overall lower MICs (MIC50/90 I/R 8/256 mg/L vs. MIC50/90 I/R+FOS 8/64 mg/L) (Fig. 1B). The isolates have diverse resistance mechanisms including KPC-producers (3/149; 4.5%), VIM-producers (19/150; 28.3%), and isolates that carry mutations in ampR, ampD, oprD, and/or pbp genes.

Conclusion
I/R + FOS lowers MICs against MDR Pae. These results lead us to postulate that inhibiting MurA enzyme that catalyzes the first committed step in peptidoglycan synthesis with FOS adds to the potency of I/R even against VIM producers.

Disclosures
Robert Bonomo, MD, Merck: Grant/Research Support|Shionogi: Grant/Research Support Gauri G. Rao, PharmD, MS, Merck: Grant/Research Support
P-1515. Outcomes of Patients with Piperacillin/Tazobactam-Non-Susceptible and Ceftriaxone-Susceptible Enterobacterales Bacteremia
Authors: Lee Michelle , O’Neill Emily , Cunha Cheston , Geffert Sara , Nering Chris , O’Rourke Emerald 
Published: January 2025

Abstract

Background
Piperacillin/tazobactam (TZP)-non-susceptible (NS) but third-generation cephalosporin (3GC)-susceptible (S) Escherichia coli and Klebsiella pneumoniae are increasingly reported in the clinical setting. This phenotype is associated with hyperproduction of β-lactamases, including TEM-1 and SHV-1. Tailoring therapy to a 3GC in these cases may decrease carbapenem use and promote antimicrobial stewardship. However, the optimal definitive β-lactam regimen for this phenotype is unknown. This retrospective case series describes the clinical outcomes and antibiotic prescribing in patients with TZP-NS and ceftriaxone (CRO)-S Enterobacterales bacteremia at a three hospital health system.

Methods
We identified patients &gt;18 years of age hospitalized with TZP-NS and CRO-S E. coli, K. pneumoniae, Klebsiella oxytoca, and Proteus mirabilis bacteremia between February 2020 and March 2024. TZP-NS and CRO-S were defined per the 2024 Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoints: TZP-S if minimum inhibitory concentration (MIC) ≤ 8/4 mg/L, TZP-NS if MIC ≥ 16/4 mg/L; CRO-S if MIC ≤ 1 mg/L, CRO-NS if MIC ≥ 2 mg/L. We included only the first isolate per patient over the study period. Antibiotic data were collected for each patient during hospitalization. We defined empiric antibiotics as the agents with the longest duration of therapy (DOT) prior to susceptibilities. Composite clinical outcomes were 30-day all-cause mortality, or 30-day readmission/emergency department (ED) visit.

Results
Thirty-nine patients were included in the study (Table 1). The median number of different antibiotics patients received was 3 (interquartile range [IQR] 2-3), and the median total antibiotic DOT was 14 days (IQR 9.5-17.5 days) (Table 2). Thirteen patients experienced a clinical outcome (33.3%) (Table 3). Of the patients who experienced a clinical outcome, 46.2% (6/13) received ceftriaxone during tailored therapy (median 4.5 days, IQR 3.3-7.3 days).

Conclusion
In this case series, most patients received TZP empirically but were tailored to CRO upon culture susceptibility availability. Larger studies are necessary to elucidate if ceftriaxone is appropriate for definitive treatment of TZP-NS and CRO-S E. coli, K. pneumoniae, K. oxytoca, and P. mirabilis bacteremia.

Disclosures
All Authors: No reported disclosures
P-1521. Susceptibility of Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA) With and Without Carbapenemases to Cefepime-Taniborbactam and Comparators: GEARS Antimicrobial Surveillance Program, United States, 2018-2022
Authors: Wise Mark G , Hackel Meredith , Sahm Daniel F 
Published: January 2025

Abstract

Background
Taniborbactam is a novel β-lactamase inhibitor that inhibits serine-β-lactamases and NDM & VIM (but not IMP) metallo-β-lactamases, restoring the activity of cefepime against most isolates of Enterobacterales and P. aeruginosa carrying these enzymes. This study examined the in vitro activity of cefepime-taniborbactam (FTB) against recent clinical isolates from the US, focusing on genotypically-characterized carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant P. aeruginosa (CRPA).

Methods
From 2018-2022, as part of the GEARS program, 4,932 Enterobacterales and 1,508 P. aeruginosa isolates were collected from 42 hospitals in the US. MICs of cefepime-taniborbactam and comparators were determined by CLSI reference broth microdilution and interpreted using 2024 CLSI breakpoints. CRE was defined by resistance to meropenem; CRPA was defined by resistance to meropenem and/or imipenem. Isolates with cefepime-taniborbactam MIC ≥16 µg/mL were characterized by whole genome sequencing. Isolates resistant to meropenem were screened for acquired β-lactamases by PCR.

Results
95.9% of the 73 CRE isolates were inhibited by ≤16 µg/mL FTB (Fig. 1). Most CRE (55/73; 75.3%) produced a carbapenemase (40 KPC, 7 NDM, 2 VIM, 2 OXA-48-like, 2 KPC+OXA-48, 1 IMP, and 1 VIM+OXA-48); 96.4% were inhibited by ≤16 µg/mL FTB and the most active comparator was meropenem-vaborbactam (80.0% susceptible). At ≤16 µg/mL, FTB inhibited 92.0% of all CRPA (n=386) and 87.2% of meropenem-resistant CRPA (n=226) (Fig. 2). Among meropenem-resistant CRPA, 6 isolates (2.7%) carried a carbapenemase (2 IMP, 1 IMP+VIM, 1 VIM, 1 GES, 1 NDM). FTB at ≤16 µg/mL inhibited 88.6% of meropenem-resistant, carbapenemase-negative P. aeruginosa and 2/3 non-IMP carbapenemase-positive isolates.

Conclusion
FTB at ≤16 µg/mL inhibited &gt;94% of CRE isolates collected in the US, regardless of carbapenemase carriage. Similarly potent activity was observed for cefepime-taniborbactam against meropenem-resistant CRPA isolates, most of which lacked a carbapenemase. Upon approval, cefepime-taniborbactam could be an important option for use against CRE and CRPA, as currently available therapies have limited activity.

Disclosures
Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
P-1552. Risk Factors For Multidrug-Resistant Klebsiella Pneumonia Urinary Tract Infections
Authors: Hammami Fatma , Rekik Khaoula , Smaoui Fatma , Chakroun Amal , Marrakchi Chakib , Koubaa Makram , Jemaa Mounir Ben 
Published: January 2025

Abstract

Background
Multidrug-resistant (MDR) Klebsiella pneumonia urinary tract infections (UTI) has increased over the past years, leading to problems in treatment and management. We aimed to study the risk factors associated with MDR Klebsiella pneumonia UTI.

Methods
We conducted a retrospective study including all patients hospitalized in the infectious diseases department for UTI caused by Klebsiella pneumonia between 2015 and 2022.

Results
We encountered 134 cases among whom 78 cases were MDR (58.2%) and 56 cases were non-MDR (41.8%). Patients with MDR UTI were significantly older (62±19 years vs 47±21 years; p&lt; 0.001). Patients aged 60 years and above (70.5% vs 37.5%; p&lt; 0.001) and male patients (46.2% vs 26.8%; p=0.023) were significantly more affected by MDR UTI. Diabetes mellitus (41% vs 21.4%; p=0.017) and renal calculi (19.2% vs 5.4%; p=0.02) were significantly more frequent among MDR UTI cases. Recent invasive urologic procedure (21.8% vs 3.6%; p=0.003), previous medical history of MDR UTI (24.4% vs 7.1%; p=0.009), antibiotics use (53.8% vs 17.9%; p&lt; 0.001) and previous hospitalization (42.3% vs 12.5%; p&lt; 0.001) were significantly more frequent among MDR UTI cases. C-reactive protein levels were significantly lower among MDR UTI cases (40[5-155] mg/l vs 224[143-288] mg/l; p=0.002). A favorable evolution of the disease was significantly more frequent among non-MDR UTI cases (87.5% vs 67.9%; p=0.009). As to complications, death and relapse, no significant difference was noted.

Conclusion
Male diabetic patients at an advanced age, with previous medical history of MDR UTI, renal calculi or recent invasive urologic procedure were at high risk of acquiring MDR UTI caused by Klebsiella pneumonia.

Disclosures
All Authors: No reported disclosures
P-1560. Risk Factors for Extended-Spectrum β-Lactamase-Producing Escherichia coli Urinary Tract Infections
Authors: Tellerman Julia , Khawly Gabriella , Looi Hsioa Che , Dietz Jenna , Myers Christopher J , Tsay Rebecca , Russ Savanah , Dumyati Ghinwa 
Published: January 2025

Abstract

Background
E. coli is the leading cause of urinary tract infections (UTIs) worldwide. Antibiotic resistance among E. coli is increasing. We performed a case-control study to identify risk factors predictive of a positive extended-spectrum beta-lactamase (ESBL)-producing E. coli (ESBL-E) compared to a non-ESBL-E urine culture.
Table 1
Demographic and clinical characteristics of patients with positive E. coli urine culture, Monroe County, August 2023

Methods
Positive E. coli urine cultures were identified via laboratory and population-based surveillance in Monroe County as part of the CDC Emerging Infections Program in August 2023. Cases were defined as a county resident with a positive ESBL-E urine culture (resistant to ≥1 3rd-generation cephalosporin and nonresistant to carbapenems). Controls had a non-ESBL-E urine culture. All ESBL-E cases and a random sample of non-ESBL-E controls underwent medical record review to collect information on prior antimicrobial use, recent hospitalization, prior ESBL-E infection, underlying conditions, and prior long term care stay. Charlson Comorbidity Index (CCI) was calculated and categorized as low (0), middle (1-2), and high (3+). Multivariable logistic regression was used to identify independent risk factors.

Results
We identified 2142 patients with an E. coli urine culture; 454 underwent chart review (64 ESBL-E, 390 non-ESBL-E). Patient characteristics are summarized in Table 1. Overall, patients were mostly female (88.3%) with a median age of 61 years (IQR 39-76). Cases more commonly received antibiotics in the 30 days prior to culture (34.4% vs. 19.7%, p = 0.007), had a hospitalization in the 90 days prior to culture (17.2% vs. 8.5%, p = 0.029), had prior ESBL-E culture (25.0% vs. 3.3%, p &lt; 0.0001), a high CCI (32.8% vs. 19.7%, p = 0.006), prior LTC stay (18.8% vs. 6.4%, p = 0.0008), and diabetes (35.9% vs. 19.5%, p=0.003). After adjusting for confounding factors, only prior ESBL-E culture (OR = 8.22; 95% CI: 3.68-18.40) and diabetes (OR = 2.32; 95% CI: 1.31-4.09) were significantly predictive of the outcome.

Conclusion
Patients with ESBL-E are more medically complex with increased healthcare exposure compared to patients with non-ESBL-E. Presence of a prior ESBL-E culture and diabetes were specific risk factors. Future studies are needed to better understand the collective impact of ESBL-E drivers to inform prevention strategies.

Disclosures
All Authors: No reported disclosures
P-1562. Epidemiology, Management, and Outcomes of a Novel Complex Urologic Infections Interdisciplinary Clinic
Authors: Kling Kendall , Zembower Teresa , Moore William Justin , Colbert Stephanie , Schaeffer Anthony , Williams Janna 
Published: January 2025

Abstract

Background
Urinary tract infections (UTIs) are the most common bacterial infections, yet patients with recurrent infection are often not offered effective preventative therapies, patients with bacterial persistence may have a urologic nidus of infection, and patients with non-infectious syndromes are often over-treated with antibiotics.

Methods
We developed a Complex Urologic Infections Interdisciplinary Clinic comprised of infectious diseases and urology physicians as well as antimicrobial stewardship pharmacists. We categorized patients as complicated (defined as abnormal urinary tract predisposing to infection) or uncomplicated and describe the first 237 patients seen 16 months after clinic initiation.

Results
Most of our patients were female (69%) and white (67%) with a mean age of 61 and a mean Charlson score of 3.3 (Table 1). Most (58%) had complicated urologic tracts with overall higher Charlson comorbidity scores. Based on a standardized clinical classification system, most presented with recurrent/reinfection (38%), but we also identified patients with isolated and intermittent infection, bacterial persistence, and non-infectious syndromes (Table 2). We started 75/89 (84%) patients with recurrent infections on prevention therapy, and 14 declined. Vaginal estrogen or methenamine monotherapy had an efficacy of 57% and 70% at a mean follow up of 4.2 and 4.6 months, respectively (Figure 1). All five patients on vaginal estrogen plus continuous prophylaxis were UTI free at a mean follow up of 5 months. We identified 20 patients with urinary bacterial persistence, ordered imaging of the urologic tract, and identified an infected urologic nidus and cured or suppressed the infection in 95%. Thirty-two percent of patients referred for UTI were found to have non-infectious syndromes, including asymptomatic bacteriuria (19%) and lower urinary tract symptoms (10%) (Figure 2). Multi-drug resistant organisms were found in 25%, 30% of which were in patients with non-infectious syndromes.

Conclusion
Complex Urologic Infections Interdisciplinary Clinics can provide expertise to prevent recurrent UTIs, identify a urologic nidus of infection in patients with persistence, and potentially reduce antimicrobial burden and resistance in patients without true infection.

Disclosures
All Authors: No reported disclosures
P-1563. Assessing the Global Economic Burden of Complicated Urinary Tract Infections
Authors: Broughton Edward I , Bektas Meryem , Colosia Ann , Kuper Kristi , Fernandez Maria , Al-Taie Amer , El Mahdy Kotb Ramy 
Published: January 2025

Abstract

Background
Complicated urinary tract infections (cUTIs) arise in patients with structural or functional abnormalities of the genitourinary tract or in those with nonurogenital comorbidities. cUTIs are common in older or catheterized persons and can be associated with high healthcare resource utilization (HCRU). We conducted a systematic literature review to understand the economic burden of cUTI.

Methods
A systematic literature review was conducted using PubMed, Embase, Cochrane, and EconLit databases to identify observational studies evaluating the burden of cUTI, including acute pyelonephritis and catheter-associated UTI (CAUTI), within the last decade from China, Europe, France, Italy, Germany, Japan, Spain, United Kingdom (UK), and United States (US) (PROSPERO-CRD42023454794).

Results
Of 1,041 studies identified, 154 from databases were selected for full-text review; a total of 53 met the economic inclusion criteria, reporting direct costs (18 US, 2 China, 2 Spain, 1 Italy) and/or healthcare utilization (28 US, 13 Spain, 4 China, 4 Italy, 3 multicountry/European region, 2 France, 1 UK). No studies of direct cUTI costs were identified for France, Germany, Japan, the UK, or Europe.
Mean hospitalization costs per cUTI varied by country, from $2,328 in China to $23,400 for hospital-acquired CAUTI in US children. The highest costs were observed in patients with multi-drug-resistant infections. US national all-cause median 30-day total healthcare costs of cUTIs were estimated at &gt; $6 billion (Table 1). No studies reporting the indirect cost of cUTI were identified, and costs associated with readmissions were reported in only 1 study.
Length of stay (LOS) was the most common HCRU outcome reported, and median LOS was similar among studies (7 days). Patients with CAUTI had longer LOS than controls. ICU admissions in patients with extended-spectrum β-lactamase (ESBL)–positive cUTI ranged between 3% and 27.4%.

Conclusion
Available data indicate that the economic burden associated with cUTI is substantial. However, except for the US, direct costs were missing or reported in only 1 or 2 studies for the countries examined. Similarly, HCRU outcomes were missing or reported in only a few studies, except for the US and Spain.

Disclosures
Edward I. Broughton, PhD, Pfizer: Ownership Interest Kristi Kuper, PharmD, BCPS, FIDSA, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Maria Fernandez, PhD, MBA, Pfizer: Stocks/Bonds (Public Company) Amer Al-Taie, MSc, Pfizer: Stocks/Bonds (Public Company) Ramy El Mahdy Kotb, MD, Pfizer: Stocks/Bonds (Public Company)
P-1564. Clinical Findings in Pediatric Patients with Renal Abscesses Treated with Intravenous versus Oral Antibiotics
Authors: Jermakian Kristine A , Olson Jared , Stallsmith Jena , Mehra Sonia , Thorell Emily A , Benvegnu Timothy , Wilcox Roger 
Published: January 2025

Abstract

Background
Renal abscesses in pediatric patients are uncommon and there is a paucity of data published regarding clinical findings and treatment outcomes. Case reports have documented the successful use of intravenous (IV) antibiotics, with or without surgical intervention. However, few case series have documented the use of enteral or oral antibiotics, specifically in the pediatric population. The treatment approach to renal abscesses in pediatric patients remains controversial.

Methods
This retrospective case study identified children less than or equal to 18 years of age in the Intermountain Health System who had a radiographically diagnosed renal or perirenal abscess between 2015 and 2023. Patient charts were retrospectively reviewed and evaluated for clinical variables and treatment strategies. Patient and clinical outcomes assessed included hospital readmission, emergency department (ED) revisits, re-occurrence of abscess within one year, and length of hospital stay.

Results
Forty-two patients were evaluated. On average, patients included had an elevated C-reactive protein and serum white blood cell (WBC) count. Escherichia coli was the main pathogen isolated from culture results (50%). Per urinalysis (UA) findings, 50% of UAs had trace or greater leukocyte esterase and 61% had trace or greater protein. Hematuria was observed in 60% of microscopic UA results, and 66% of UAs had WBCs greater than five. The majority of patients (81%) were sent home on oral antibiotics. Of the patients sent home on IV antibiotics, 71% of patients had an oral option. Readmission within 90-days was seen in 6% of patients on oral therapy and 14% of patients on IV therapy (P = 0.48). ED revisit within 90-days was seen in 6% of patients on oral therapy versus 14% of patients on IV therapy (P = 1.00). No patients had a re-occurrence of abscess within one year (P = 1.00). The median length of stay in the oral therapy group and IV therapy group was 3 days (2, 5.75) and 5.5 days (3.5, 8.75) (P = 0.13), respectively.

Conclusion
No patients had a re-occurrence of abscess within one year. 71% of patients treated with IV antibiotics had an oral option and were treated with an IV antibiotic based on provider preference. Oral antibiotics appear to be effective in the treatment of renal abscesses.

Disclosures
All Authors: No reported disclosures
P-1584. Diagnostic Stewardship of Cerebrospinal Fluid Testing: Impact on Quantity of Tests, Length of Stay, Antibiotic Prescriptions, and Cost
Authors: Pathak Aaron , Shay Sabra , Lasco Todd M , Al Mohajer Mayar 
Published: January 2025

Abstract

Background
While cerebrospinal fluid (CSF) cultures are the primary test of choice for meningitis, physicians can order a plethora of additional tests with varying levels of utility and cost. Some of these tests frequently have a high financial burden with little clinical impact. This study aims to assess whether limiting available CSF tests impacted the length of stay, empiric days of therapy (eDOT), and cost of testing in patients who received a lumbar puncture (LP) with subsequent infectious disease testing.Figure 1.Number of tests performed (negative binomial regression)

Methods
Our quasi-experimental study included patients from a quaternary academic medical center in Texas who received an LP with subsequent infectious disease testing. CSF testing was not restricted in the pre-intervention period (May 2023 - October 2023). In the post-intervention phase (December 2023 - February 2024), physicians were limited to ordering cell CSF count and differential, gram stain/bacterial culture, cryptococcal antigen, glucose, protein, meningitis/encephalitis panel, and VDRL if a serum RPR test was positive. Other CSF testing required consultation with the infectious disease team. Regression models were fitted to assess the impact of the intervention on study outcomes (negative binomial for the number of tests per patient, linear regression for the squared root of testing cost per patient and log length of stay, and zero-inflated negative binomial for eDOT).Figure 2.Squared root costs of tests performed (linear regression)

Results
A total of 245 patients were included (158 pre-intervention and 85 post-intervention). After adjusting for confounders, the intervention did not significantly reduce the number of tests per patient (IRR= .83, p = .063, Figure 1), the squared root cost of tests per patient (B= 3.46, p = .068, Figure 2), eDOT (IRR= .55, p = .102, Figure 3) or the log length of stay (B= .14, p = .461, Figure 4).Figure 3.Empiric days of therapy (count and zero-inflated model)

Conclusion
This intervention did not reduce the number of tests ordered or the cost of testing for patients with suspected meningitis. The decrease in unapproved tests was balanced by an increase in approved tests, with increased use of the meningitis/encephalitis panel preventing cost reduction. Future diagnostic stewardship interventions should limit expensive tests such as the meningitis/encephalitis panel to patients with a reasonably high pre-test probability.Figure 4.Logarithmic transformed length of stay (linear regression)

Disclosures
All Authors: No reported disclosures