bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1508. In Vitro Activity of Aztreonam-avibactam against Enterobacterales Isolates Producing Multiple β-lactamases Collected Globally as a Part of the ATLAS Global Surveillance Program from 2018-2022
Authors: Estabrook Mark , Li Henry , Stone Gregory , Perez Katherine , Sahm Daniel F
Published: January 2025

Background

Aztreonam-avibactam (ATM-AVI) is a β-lactam/β-lactamase inhibitor combination to treat infections caused by Gram-negative organisms, particularly those carrying metallo-β-lactamases (MBLs) and other β-lactamases. Aztreonam is stable to hydrolysis by MBLs and avibactam inhibits Class A, C, and some Class D enzymes. We examined ATM-AVI activity against Enterobacterales isolates producing one or more β-lactamase collected as a part of the ATLAS global surveillance program (2018-2022).

Methods

88,750 isolates from 227 medical centers in 57 countries (excluding mainland China, Canada, and the USA) were collected and tested for susceptibility using the broth microdilution method according to CLSI guidelines. Analysis was performed with CLSI 2024 breakpoints. Isolates testing with meropenem MIC values >1 µg/mL or Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or Proteus mirabilis isolates testing with ceftazidime and/or aztreonam MIC values >2 µg/mL were screened for β-lactamase genes by PCR, which were sequenced when identified.

Results

One or more extended-spectrum β-lactamase (ESBL), serine-carbapenemase, MBL, or acquired AmpC was identified among 17,013/18,408 isolates characterized. Among isolates carrying one or two ESBLs (51.4%), 99.9-100% tested with ATM-AVI MICs ≤8 µg/mL (MIC90 values of 0.12 and 0.5 µg/mL, respectively). Among isolates with a serine-carbapenemase and one or more ESBL (18.3%), 99.9-100% tested with ATM-AVI MICs ≤8 µg/mL (MIC90 values of 0.5-1 µg/mL). MBL-positive isolates with or without serine-carbapenemases and/or ESBLs (13.7%) demonstrated MICs ≤8 µg/mL among 98.3-100% of isolates in each category (MIC90 values of 0.5-1 µg/mL). Isolates carrying acquired AmpC as well as any combination of additional β-lactamases (9%) tested with ATM-AVI MICs ≤8 µg/mL among 93.6-100% of each population (MIC90 values of 0.5-8 µg/mL).

Conclusion

ATM-AVI demonstrated potent in vitro activity against Enterobacterales isolates regardless of the number of β-lactamases carried. Slightly reduced potency was observed in populations that carried acquired AmpC. This may be expected as some variants of AmpC with extended-spectrum activity are known to increase ATM-AVI MICs.

Disclosures

Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Henry Li, MS in Biotechnology, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
P-1510. In Vitro Activity of Ceftibuten-Avibactam and Comparator Agents Against Enterobacterales Collected Globally as Part of the ATLAS Surveillance Program, 2022 by Region
Authors: Estabrook Mark , Dickson Julie , Stone Gregory , Perez Katherine , Sahm Daniel F
Published: January 2025

Background

Ceftibuten is an orally administered third-generation cephalosporin in clinical development in combination with an oral prodrug of avibactam, an inhibitor of class A β-lactamases, including ESBLs and KPC, class C (AmpC) β-lactamases, and some class D (OXA-48) β-lactamases. This study evaluated the in vitro activity of ceftibuten-avibactam and comparators against Enterobacterales isolates collected globally as part of the 2022 Antimicrobial Testing Leadership and Surveillance (ATLAS) program, by region.

Methods

23,088 non-duplicate clinical Enterobacterales isolates were collected in 2022 from 217 medical centers in 56 countries. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2024 breakpoints. Ceftibuten was tested with a fixed concentration of 4 µg/mL avibactam.

Results

Ceftibuten-avibactam was active at ≤1 µg/mL against more isolates than were susceptible to any oral comparator agent (87.3-97.5%). Ceftibuten-avibactam also demonstrated the lowest MIC90 values, by region among the oral agents tested. Regional differences in the in vitro activity of ceftibuten-avibactam were observed with a lower MIC90 value against isolates collected in Europe, North America, the South Pacific, and the Middle East (0.12-0.25 µg/mL) as compared to Latin America, Asia, and Africa (0.5, 4, and 16 µg/mL, respectively). This phenomenon was also observed among oral comparator agents, with fewer isolates collected in Africa susceptible to cefixime (40.8%), cefpodoxime (42.5%), levofloxacin (48.7%), and trimethoprim-sulfamethoxazole (37.8%) than in any other region. A similar pattern was observed for the intravenously administered ceftazidime-avibactam, with 89.3% of isolates collected in Africa susceptible.

Conclusion

Based on these data, ceftibuten-avibactam demonstrates promise as a candidate for oral treatment of infections caused by Enterobacterales. Regional trends in antimicrobial resistance to a diverse range of agents warrant continued monitoring.

Disclosures

Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Julie Dickson, BS, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
P-1511. In Vitro Activity of Gepotidacin Against Molecularly Characterized Neisseria gonorrhoeae Isolates Exhibiting Reduced Susceptibility to Antibacterial Agents, 2018-2021
Authors: Estabrook Mark , Kapoor Renuka , Torumkuney Didem , Li Henry , Sahm Daniel F
Published: January 2025

Background

Gepotidacin (GEP) is a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial that inhibits bacterial DNA replication by a unique mechanism of action, distinct binding site, and provides a well-balanced inhibition (for most uncomplicated urinary tract infection (uUTI) uropathogens and N. gonorrhoeae)) of two different Type II topoisomerase enzymes. We present the activity of GEP against molecularly characterized N. gonorrhoeae isolates collected from patients in Australia, India, and the United States from 2018-2021 as part of a GEP global gonococcal surveillance study.

Methods

N. gonorrhoeae isolates were tested for susceptibility to GEP and comparator agents by CLSI agar dilution method and analyzed using CLSI 2024 breakpoints. Isolates that met predefined selection criteria, which included GEP MIC values >1 µg/mL or nonsusceptible or resistant (R) to select comparators, were characterized by whole genome sequencing.

Results

A total 711 N. gonorrhoeae isolates were collected and of these 341 (48%) were characterized. The GEP MICs for both populations of isolates ranged from ≤0.06 to 2 µg/mL; MIC90 of 1 µg/mL (Table 1). Of 324 ciprofloxacin-R isolates, 105 (32.4%) had a mutation of D86N in ParC; this mutation was associated with a GEP MIC90 of 2 µg/mL (range= 0.25-2 µg/mL). Isolates with this mutation also carried mutations in the quinolone-resistance determining region (QRDR) of GyrA as well as mutation(s) suggesting the upregulation of the MtrCDE efflux pump. When categorizing isolates by QRDR mutation, ParC D86N was the only mutation associated with a GEP MIC90 >1 µg/mL. A myriad of resistance mechanisms relevant to penicillin, azithromycin, and tetracycline, were identified among the characterized isolates, against which GEP MIC90s ranged from 1-2 µg/mL (Table 2).

Conclusion

GEP demonstrated potent in vitro activity against N. gonorrhoeae isolates, including those that were not susceptible to comparator agents. GEP’s MIC90 value relative to all isolates, and those with other QRDR mutations in this study, was one dilution higher (2 versus 1 µg/mL) against isolates that carried ParC D86N, which is known to be important for GEP binding.

Disclosures

Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Didem Torumkuney, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Henry Li, MS in Biotechnology, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
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

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

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 >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

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 >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

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< 0.001). Patients aged 60 years and above (70.5% vs 37.5%; p< 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< 0.001) and previous hospitalization (42.3% vs 12.5%; p< 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

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 < 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

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

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 > $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

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

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
P-1587. The Utility of Using FilmArray Meningitis-Encephalitis PCR Panel (MEP) in Children Admitted with Meningitis and Encephalitis at LUMC. Is it a Useful Diagnostic Stewardship Tool?
Authors: AL-Sayyed Ban H , Covington Kelli , Nicoski Pamela , Feffer Marina , Heyn Madeleine , Hunter-McElroy Gabriella , Pal Shibangi , Lie Louise , Mannaa Jenin
Published: January 2025

Background

MEP allows for rapid detection or exclusion of pathogens causing meningitis and encephalitis (ME) in neonates and children. Studies showed its high sensitivity and specificity as a tool in diagnosing ME and reducing duration of antibiotics. We conducted a retrospective study in our institution to evaluate MEP usage in our pediatric population suspected to have ME, assess the agreement between MEP and CSF culture and cell count results, and measure the impact of MEP results on discontinuing empiric antimicrobials.

Methods

We reviewed electronic records of patients aged 0–18 years admitted with possible ME from January 1, 2019 to April 30, 2023. We excluded patients with VP shunt infections and malfunctions, immunocompromised hosts, patients who did not receive antibiotics, and cases who had CSF culture done without MEP on admission.

Results

We included 136 patients admitted with possible ME and treated with antibiotics. Of all patients, 6.5% had viral PCR detected (n=9), 3.7% had bacterial PCR detected (n=5), 89% had negative PCR (n=122). Antibiotics were started before lumbar puncture in 77% of cases (n= 105). Only 23% were tapped before initiation of antibiotics (n = 31). There was 99.2% positive agreement between MEP and CSF culture results after viral isolates were removed (n=126/127). CSF pleocytosis was present in 19.4% of cases (n=25/129), and results were discordant with MEP in 17.1% of cases (n=22/129). Empiric vancomycin was started in 37% of patients who had no additional focus of infection on admission (n=41/111), and was discontinued within 12 hours of MEP results in 51% of cases (n=21/41). Empiric antibiotics were discontinued within 36 hours of negative MEP results in 31.5% of cases (n=35/111). Acyclovir was combined with antibiotics empirically in 13.5% of cases only (n=15/111).

Conclusion

MEP is an important diagnostic stewardship tool. It is highly sensitive and specific in diagnosing ME in children. However, agreement with CSF cultures might be limited by antibiotic treatment prior to lumbar puncture. MEP helps in quick de-escalation of empiric antibiotics and reduces unnecessary prolonged therapy in children treated with antibiotics before obtaining CSF. Using CSF pleocytosis as an indication for MEP testing has a low yield.

Disclosures

All Authors: No reported disclosures
P-1611. Clinical Evaluation of the Selux Rapid Next Generation Phenotypic Antimicrobial Susceptibility System for both Direct-from-Colony and Positive Blood Cultures
Authors: Morgan Margie A , Smith Stuart G , Contreras Deisy
Published: January 2025

Background

The Selux next-generation phenotyping (NGP) system (SeluxDx) utilizes a proprietary 384-well panel for Gram-positive and Gram-negative antibiotic susceptibility testing available direct-from-colony and Gram-negative from positive blood culture.

Methods

Previously tested bacteria on the Phoenix M50 were used for direct-from-colony assessment. Gram-negative (n=100) and Gram-positive (n=30), were grown on 5% sheep’s blood agar plates and incubated overnight at 35oC. Testing dilution was prepared in saline in the range of 0.4-0.6 McFarland and then inoculated into either the Gram-positive or Gram-negative panel utilizing the system’s automated inoculator platform. Positive blood cultures were concentrated using the Selux Separator automated platform and a pre-prepared McFarland sample was generated to inoculate the Gram-negative panel, and a viable bacterial pellet produced for identification testing. All panels were processed using the Selux Analyzer platform and categorical and essential agreement was calculated for FDA approved bug-drug combinations.

Results

The overall essential agreement for the Gram-negative panel was 97% (97/100) and categorical agreement was 94% (94/100). Two very major errors included Ertapenem in an Escherichia coli and an Enterobacter cloacae complex isolate where the Selux system failed to detect resistance. For the Gram-positive panel, categorical agreement was found to be 96.7% (29/30) with one very major error in Staphylococcus aureus for Clindamycin. Selux generated an AST result for 98% (40/41) of the concentrated blood culture samples. The overall categorical agreement between Selux and the Accelerate Pheno® system was 93%. Major discrepancies (2.4%) and very major discrepancies (4.8%) detected involved the testing of Piperacillin/Tazobactam. The pellet generated an identification to species on 45/48 (94%) of samples using the Bruker MALDI Biotyper®.

Conclusion

The Selux NPG system proved to be a reliable rapid automated platform for both Gram-negative and Gram-positive isolates from direct-from-culture and for rapid AST from positive blood culture Gram-negative isolates. The 384-well panel allows for future adaption of novel antimicrobial agents to meet the demand of an ever-changing resistance landscape.

Disclosures

All Authors: No reported disclosures
P-1616. Treatment Rates of Patients with Toxin Negative, PCR Positive C.difficile After a Change in Reflex Testing Order
Authors: Berke Marten , Miller Molly M , Ringsdorf Brook A , Hankins Richard , Van Schooneveld Trevor C , Bergman Scott J
Published: January 2025

Background

On 12/11/23, our academic medical center changed from primarily GDH antigen/toxin A/B combination testing with reflex to C. difficile PCR in discordant samples (Figure 1) to PCR (either direct or from a multiplex gastrointestinal pathogen panel (GIPP)) as initial screening with positive specimens reflexed to antigen/toxin testing (Figure 2). After the algorithm change, we evaluated treatment rates for patients with positive PCR results who tested negative for C. difficile toxin.

Methods

New guidance for C. difficile infection (CDI) was posted on the Antimicrobial Stewardship website and education was provided to clinicians on the algorithm. Data was collected for inpatients ≥ 19 years old who were toxin negative, but antigen and PCR test positive for C. difficile from 10/1/22-3/31/24. GIPP could be ordered first during the entire period, but only in the first 3 hospital days. Treatment and recurrence rates for patients having a PCR test first were analyzed compared to rates for those with initial antigen/toxin tests. Treatment was counted if initiated within 2 days of test and continued ≥ 5 days, according to proposed NHSN definitions, and included oral vancomycin, fidaxomicin, or metronidazole if vancomycin was contraindicated. Based on estimated treatment rates, a sample size of 177 patients was targeted to detect a change from 80% to 60% treatment.

Results

Out of 179 discordant CDI results prior to the testing change, treatment occurred in 151 (85.4%) cases. After the change, treatment was prescribed 26 out of 46 (56.5%) times, a 34% reduction (p< 0.01). Baseline characteristics were similar in each group, and 56.9% of tests were ordered in the first 3 days of hospital stay. Overall, when an antigen test was performed first and a positive PCR reported last, treatment occurred in 84 of 91 (92.3%) cases. When a PCR test was performed first and a negative toxin resulted last, treatment was prescribed in 93 of 134 (69.4%) cases (p< 0.01). Treatment was the same in each group (99% vancomycin). Recurrence rates were similar regardless of testing order, 5.4% with antigen first vs. 4.4% with PCR test first.

Conclusion

Treatment rates for patients with discordant CDI results were significantly lower after the order of testing changed and when a negative toxin result was presented last.

Disclosures

Trevor C. Van Schooneveld, MD, FSHEA, FIDSA, AN2 Therapeutics: Grant/Research Support|BioMerieux: Grant/Research Support|BioMerieux: Honoraria|Thermo-Fisher: Honoraria
P-1619. Diagnostic Stewardship: Over-testing for Herpes Simplex Virus in Bronchoalveolar Lavage Specimens
Authors: Lin Oliver , Burnette Bailey , Reece Becky
Published: January 2025

Background

HSV-1 is estimated to affect 3.7 billion worldwide (67% prevalence), primarily manifesting as oropharyngeal lesions. Although HSV can be commonly detected by polymerase chain reaction (PCR) in bronchoalveolar lavage (BAL) specimens, true HSV pneumonitis is rare and most positive specimens reflect colonization or asymptomatic reactivation, not active respiratory infection. This study evaluates the appropriateness and frequency that diagnostic HSV-1/2 qualitative DNA PCRs are ordered on BAL specimens at a tertiary medical center and its impact on treatment and patient outcomes.

Immune Status of Patients Tested for Opportunistic Infections

Methods

Patients at a single tertiary medical center who had HSV-1/2 qualitative DNA PCR performed on any specimen in 2022 were identified by lab order. Testing performed on non-BAL specimens were excluded from data collection. De-identified clinical history, risk factors, immune status, concomitant testing, treatment, and outcomes were recorded to secure database for analysis.

Immune Status Guiding Treatment in HSV Positive Patients

Results

HSV-1/2 qualitative DNA PCR testing was performed on BAL specimens from 131 unique patients. Of the 131 patients, 50 (38.2%) were immunosuppressed as defined by active malignancy, pharmacologic immunosuppression, neutropenia, HIV positive thus most testing was performed on immunocompetent patients without risk factors. 16 patients had a positive qualitative PCR (12.2%) of which 6 patients were treated with antiviral therapy (4.6%). 12 patients (9.2%) were tested more than once on different occasions, 4 of which were positive. 1 patient had a documented final diagnosis of HSV pneumonitis treated with acyclovir.

Conclusion

HSV pneumonitis is a rare manifestation of a common infection that is associated with critical illness, poor outcomes. Many patients will have positive PCR testing of BAL specimens due to inoculation from the upper respiratory tract but this typically does not reflect true infection. Only in the context of significant immunosuppression, compatible clinical presentation can HSV pneumonitis be diagnosed. Excessive ordering of HSV testing leads to unnecessary healthcare expenditure and confounds the clinical picture and decision making. We suggest limiting HSV testing to immunosuppressed patients with the appropriate clinical presentation and use of cytopathology to help confirm diagnosis.

Disclosures

All Authors: No reported disclosures
P-1620. Use of Multiplex PCR and Antimicrobial Stewardship Intervention to Optimize Antimicrobial Therapy in Pneumonia Patients at a Community Teaching Hospital
Authors: Politis Paula A , England Matthew , File Thomas M
Published: January 2025

Background

Patients admitted to the hospital with community-acquired pneumonia (CAP) or those who develop hospital-acquired pneumonia (HAP) are usually treated with broad spectrum antimicrobials for several days while awaiting the results of gold standard respiratory culture. Recently, our health system instituted a rapid Pneumonia PCR Panel (PN) that has increased the yield of pathogen-specific, actionable results in significantly less time than culture allowing for faster optimization of antimicrobial therapy. Our Antimicrobial Stewardship Program (ASP) routinely follows and provides recommendations based on the results of the PNs. The purpose of our quality improvement project was to assess the optimization of antimicrobial therapy associated with use of the PNs and ASP intervention.

Table 1

Methods

We performed a retrospective review of patients admitted to our institution on whom ASP intervened with a PN performed for the timeframe of January 2023-March 2023. We assessed ASP intervention type, respiratory culture and PN results, and patient location.

Results

There was a total of 91 patients with PNs/respiratory cultures evaluated. 52 (57%) patients were in the ICU. 38% of cultures were positive with > 1 bacterial organism isolated whereas 82% of PNs were positive with > 1 organism identified. 34/35 of positive cultures had the same organism identified on PN. Of negative cultures (no growth, flora, or C. albicans), 42/56 had a positive PN for a potential pathogen, including viruses and/or bacteria. Microorganisms identified by PN in culture negative cases are listed in Table 1. In 73% of patients, the PN lead to recommendations by the ASP for more appropriate antimicrobials. Interventions included: de-escalation (50), change antibiotic for better coverage (21), duration of therapy (32), discontinue antibiotic (3), other (5), and recommend initial PN (9). In cases where ASP recommended the PN, 6 patients were appropriately covered or de-escalated by the medical team, 2 had ASP intervention, and 1 patient expired.

Conclusion

The use of the PN increased the yield of potential etiologic pathogens in patients with CAP and HAP, and when paired with ASP recommendations led to overall optimized antibiotic use and enhanced antimicrobial stewardship.

Disclosures

Thomas M. File, Jr., MD, MSc, MACP, FIDSA, Eagle Pharmaceuticals: Member of DSMB for clinical trial|MicroGenDx: Advisor/Consultant|Nabriva: Advisor/Consultant|Paratek Pharmaceuticals: Advisor/Consultant|Pfizeer: Grant/Research Support|shionogi: Advisor/Consultant|thermoFisher Scientific: Advisor/Consultant
P-1621. Utilization of Repeated Procalcitonin Assays at A Tertiary Care Center
Authors: Andrade Reema , Norman Sarah J , Ramdeen Sheena
Published: January 2025

Background

Procalcitonin (PCT) is a biomarker which has been shown to be safe and effective for reducing antibiotic exposure in patients with respiratory infections and sepsis. In current clinical practice, PCT has become a promising new biomarker for the early detection of systemic bacterial infections. In 2017, the US Federal Drug Administration (FDA) approved its use to guide antibiotic stewardship efforts in people with these conditions. Prior studies have also found value in repeated PCT measurements to inform antibiotic use in the first few days of empiric treatment. Although the use of PCT has steadily increased, failure to use the results in clinical decision-making limits its utility in antibiotic stewardship. The purpose of this study was to describe how repeated PCT tests are utilized at a large tertiary care center to guide antibiotic stewardship.

Methods

There were 1,002 patients between April 2023 and October 2023 who had a PCT test ordered, including 116 with two or more tests. Fifty of those with at least two PCT tests were selected randomly for a retrospective chart review and analysis.

Results

The median age of the cohort was 57 years, with 26 (52%) males and 24 (48%) females. Twenty-six patients received antibiotics before the PCT was tested, and 24 did not. Among the patients with at least two PCT tests, antibiotics were discontinued in 11 (22%), continued in 13 (26%), escalated in 14 (28%), and de-escalated in 6 (12%). Nine (53%) of the patients whose antibiotics were discontinued or de-escalated had PCT values that improved on repeat tests, and eight (43%) had PCT values that increased. The most common infectious diseases diagnosis was pneumonia, and three patients had more than three concurrent infections. Twenty patients had more than two PCT tests ordered. The median length of stay was 33 days, and ten patients died during their hospitalization.

Conclusion

Having more than one PCT test may be helpful in clinical decision-making and guiding antibiotic stewardship efforts, but it did not appear to have a major impact in reducing antibiotic use in this cohort. The study findings support the need for further optimization of PCT testing to aid in antibiotic stewardship at this center.

Disclosures

All Authors: No reported disclosures