bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1496. Retrospective Study of Ceftazidime-Avibactam Treatment for Multidrug-Resistant Gram-Negative Bacterial Infections in King Chulalongkorn Memorial Hospital
Authors: Jutivorakool Kamonwan , Reinprayoon Rongpong
Published: January 2025

Background

Antimicrobial resistance, particularly among Enterobacterales, poses a significant healthcare threat. With the rise of carbapenem-resistant strains, alternative treatment strategies are necessary. This study explores the clinical experience of using ceftazidime-avibactam (CAZ-AVI) in treating infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), including carbapenem-resistant pathogens.Table 1.Baseline characteristics of the patients who received CAZ/AVI

Methods

A single-center retrospective observational study was conducted at King Chulalongkorn Memorial Hospital, Thailand, from Jan. 2019 to Dec. 2022. The study included adult patients aged ≥18 years, who receiving ≥48 hours of CAZ-AVI for documented MDR-GNB infections. Data on demographics, comorbidities, treatment regimens, and outcomes were extracted from electronic medical records. The primary outcome was all-cause mortality at 14 days. Secondary objectives included clinical and microbiological responses at 14 days, and all-cause mortality at 28 days.Table 2.Clinical outcomes of the patients who received CAZ/AVI

Results

Among 85 patients receiving CAZ-AVI, 75 met inclusion criteria. The mean age was 65.27 years, with 54.7% being male. Hospital-acquired infections accounted for 82.7%, and 56% were ICU patients. Underlying conditions included chronic kidney diseases/end-stage renal diseases (28%), solid tumors (24%), cirrhosis (13.3%), hematologic malignancies (10.7%), and solid organ transplantation (10.7%). K. pneumoniae was the most common organism (69.3%), followed by P. aeruginosa (20%). All (100%) of K. pneumoniae and E. coli were carbapenem resistance. CAZ-AVI susceptibility was observed in 93.6% of isolates. The 14-day all-cause mortality rate was 25.3%. Clinical and microbiological response rates were 70.7% and 65.3%, respectively. Infection by CAZ-AVI-susceptible organisms correlated with lower mortality rates (p=0.017). No adverse drug effects were reported.Table 3.Clinical outcomes of the patients who received CAZ/AVI

Conclusion

This study highlights the promising role of CAZ-AVI in treating MDR-GNB infections, offering an alternative to conventional therapies. While challenges remain, including the complexity of empirical therapy and variations in patient outcomes, CAZ-AVI demonstrates efficacy with a favorable safety profile.

Disclosures

KAMONWAN JUTIVORAKOOL, MD, Msc, Pfizer, Thailand: Grant/Research Support|Pfizer, Thailand: Honoraria Rongpong Reinprayoon, MD, MSc, Pfizer: Grant/Research Support
P-1498. Contezolid is Active against Methicillin-Resistant Staphylococcus aureus in Experimental Rat Foreign Body Osteomyelitis
Authors: Karau Melissa J , Herren Sebastian , Koscianski Christina , Greenwood-Quaintance Kerryl , Mandrekar Jay , Patel Robin
Published: January 2025

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of orthopedic implant-associated infection, where S. aureus can survive intracellularly and form biofilms. Vancomycin has poor activity against staphyloccoccal biofilms. Although rifampin is effective against staphylococcoal biofilms and has intracellular activity, resistance may develop when it is used as a single agent. Contezolid is a novel oxazolidinone with reported activity against S. aureus in vitro and in vivo in both murine systemic and thigh infection models. Here, we assessed the in vivo activity of contezolid, with and without rifampin, in a rat model of foreign body osteomyelitis.

Figure 1.

Quantities of MRSA IDRL-6169 recovered from A. tibia B. K-wire. Circles represent values from individual animals; horizontal lines represent mean values. Compared to no treatment: *p=0.0186 **p<0.0002

Methods

The left tibia of 60 male Wister rats were inoculated with arachidonic acid (sclerosing agent) and 106 cfu MRSA IDRL-6169 and a K-wire implanted. After four weeks, rats received either no treatment, contezolid (50 mg/kg orally, every 12 h), rifampin (10 mg/kg intraperitoneally every 12 h), rifampin plus contezolid, or vancomycin (75 mg/kg intraperitoneally, every 12 h) plus rifampin for 21 days. Following treatment, tibiae were harvested and cyropulverized. Tibiae and K-wires were cultured separately, and results reported as log10 cfu/gram of bone or K-wire (limit of detect 0.1 log10), respectively. Wilcoxon rank-sum test and false discovery rates were performed and p< 0.05 considered significant.

Results

Results are shown in Figure 1. MRSA was recovered from tibiae and K-wires of all untreated animals, at means of 5.1 log10 cfu/bone and 3.0 log10 cfu/K-wire, respectively. There was a 1.0 log10 cfu/g mean reduction in MRSA recovered from the tibiae of contezolid-treated rats compared to untreated rats (p=0.0186), and a 0.2 log10 reduction on K-wires. No MRSA was recovered from the tibiae or K-wires in animals receiving rifampin, whether alone or in combination with contezolid or vancomycin.

Conclusion

Contezolid was active against MRSA in a rat model of foreign body osteomyelitis, reducing bacterial loads in bone, albeit not on K-wires, unless co-administered with rifampin.

Disclosures

Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria
P-1507. In Vitro Activity of Ceftazidime-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

Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/β-lactamase inhibitor combination approved to treat infections caused by Gram-negative organisms. Notably, CAZ-AVI has activity against Enterobacterales producing Class A, C, and D β-lactamases, but not Class B metallo-β-lactamases (MBLs). The in vitro activity of CAZ-AVI and comparator agents against clinical Enterobacterales isolates producing one or more β-lactamase collected as a part of the ATLAS global surveillance program (2018-2022) was evaluated.

Methods

89,316 isolates from 228 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), acquired AmpC, serine-carbapenemase, or MBL was identified among 17,348/18,798 isolates characterized. Against isolates producing ESBLs (51.1%), susceptibility to CAZ-AVI was similar if the isolate carried one ESBL (99.4%) or two ESBLs (98.4%). Against acquired AmpC-producing isolates (5.9%), CAZ-AVI susceptibility was similar if the isolates co-carried 0, 1, or 2 ESBLs (98.9%, 97.1%, and 100% susceptible, respectively). Against isolates carrying serine-carbapenemases (18.6%), CAZ-AVI activity was similar regardless of co-carriage of acquired AmpC and/or one or more ESBLs (95.5-100% susceptible). CAZ-AVI was not active against isolates that carried an MBL (16.6%), regardless of other enzyme carriage (0-2.9% susceptible).

Conclusion

These results highlight that the number of distinct β-lactamases have little association with susceptibility to CAZ-AVI, while the type of β-lactamase (MBL or non-MBL) has a greater association.

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-1523. Evaluation of Standardized Treatment Regimens for Patients with Documented Melioidosis Septicemia at Tertiary Care Hospital in Thailand
Authors: Pudpong Korawan , Gatechan Tipanong
Published: January 2025

Background

Burkholderia pseudomallei (B. pseudomallei), an environmental Gram-negative bacterium, is the causative agent of melioidosis in humans. Therefore, its biothreat potential, the U.S. Centers for Disease Control and Prevention designates it as a tier 1 select agent.

Melioidosis is predominantly a disease in subtropical and tropical regions. It is endemic in northern Australia and parts of Southeast Asia and the Indian subcontinent. Mostly, melioidosis (85%) results in acute infections from recent bacterial exposure. The majority of patients with acute melioidosis present with sepsis with or without pneumonia, or localized abscesses, regardless of the route of infection.

Currently, therapy consists of an intensive phase of a minimum of 10 days with intravenous ceftazidime or a carbapenem (meropenem or imipenem), with or without trimethoprim-sulfamethoxazole to prevent mortality followed by an eradication phase with oral antibiotics to prevent relapse.

In Thailand, still found the mortality rate was 40%.We have uncleared study clinical outcomes comparable to ceftazidime and carbapenems treatment in documented melioidosis septicemia.

This is the first study to evaluate the efficacy of ceftazidime compared to carbapenems in patients with documented melioidosis septicemia whose blood cultures confirmed B. pseudomallei and susceptible to both ceftazidime and carbapenems in Thailand.

Baseline characteristic (N=264)

Methods

A retrospective study was conducted at Sunprasitthiprasong hospital, Thailand from 2021-2023. Adult patients who were admitted had documented positive B. pseudomallei septicemia and received ceftazidime or carbapenem at least one dose. The exclusion criteria were incomplete chart summary. Significant level p-value≤0.05 (STATA version 16)

ceftazidime versus carbapenems in non-septic shock patients

p-value < 0.001

Results

264 patients were included and reported B. pseudomallei septicemia susceptibility to ceftazidime and meropenem were 264 (100%) pathogens and imipenem/cilastatin 262 (99.24%) pathogens.

ceftazidime versus carbapenems in septic shock patients

p-value =0.034

Conclusion

Ceftazidime compared to carbapenems in the intensive phase for documented melioidosis septicemia trends higher survival rate in 14 days after confirming pathogens in non-severe patients. Furthermore, randomized controlled trials (RCTs) will prove clinical outcomes in documented melioidosis septicemia.

Factors associated with mortality

Disclosures

All Authors: No reported disclosures
P-1532. Surveillance of Eravacycline Against Clinical Pathogens, Including Resistant Isolates, Collected Worldwide from Multiple Infection Sites During 2018-2022
Authors: Hawser Stephen , Monti Federica , Siegert Sherry , Zappas Kristie , McLeod Sarah , Moussa Samir H
Published: January 2025

Background

Eravacycline is a fully synthetic, fluorocycline antibiotic approved for the treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age in Europe, Singapore, China, Taiwan, Hong Kong, the US and the UK. The purpose of this study was to monitor the in vitro activity of eravacycline against isolates collected from a global surveillance study from 2018-2022. A total of 35,336 isolates were collected of which data for 23,127 isolates comprising Staphylococcus aureus (including methicillin-resistant S. aureus, MRSA), Enterococcus spp. (including vancomycin-resistant Enterococcus, VRE) and Streptococcus spp., Enterobacterales (C. freundii, E. cloacae, E. coli, K. oxytoca and K. pneumoniae) and non-fermenters are reported.

Methods

A total of 23,127 clinical isolates were collected during 2018-2022 from multiple infection sources, including, IAI, body fluids, blood, gastrointestinal, genitourinary and respiratory. The isolates were from Asia/Pacific (n=4,812), Europe (n=9,606) and North America (n=8,709). Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. For comparative purposes, isolate susceptibility for eravacycline and tigecycline was determined with both FDA and EUCAST breakpoints, where available.

Results

Summary MIC data for eravacycline and tigecycline as a selected comparator are shown in the Table. Susceptibility to eravacycline in all Gram-positive pathogens were greater than 90% for most species /phenotypes though was notably higher when EUCAST breakpoints were applied to the analysis. For Enterobacterales, eravacycline susceptibilities were consistently >93% though MDR susceptibility was slightly lower (84.2% susceptible to eravacycline).

Conclusion

Eravacycline demonstrated sustained high activity rates against clinically important pathogens. Importantly, the MIC90 and susceptibilities did not change over time and were similar for the different geographical regions.

Disclosures

Sherry Siegert, PharmD, Innoviva Specialty Therapeutics: Stocks/Bonds (Public Company)|Innoviva Specialty Therapeutics, Inc.: Employee Kristie Zappas, PharmD, Innoviva Specialty Therapeutics, Inc.: Employee Sarah McLeod, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds (Public Company) Samir H. Moussa, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds (Public Company)
P-1534. The Impact of Broad-spectrum Antimicrobials in Patients with Community-onset Pneumonia at Low Risk of Drug-resistant Pathogens: A Historical Cohort Study
Authors: Takazono Takahiro , Hosogaya Naoki , Saito Yoshiyuki , Takemura Masahiko , Iwanaga Naoki , Sakamoto Noriho , Hirayama Junichi , Ueno Rie , Mukae Hiroshi
Published: January 2025

Background

The administration of broad-spectrum antimicrobials has prevailed in the clinical management of community-onset pneumonia (COP). Growing evidence suggests that the use of unnecessary broad-spectrum antimicrobials for patients with COP leads to adverse events and poor outcomes. This study aims to understand the impact of broad-spectrum antipseudomonal β-lactam use on clinical outcomes and resource utilization in patients hospitalized for COP with a low risk for drug-resistant pathogens (DRPs).

Methods

This historical cohort study analyzed the hospital claims database in Japan from January to December 2018. The study includes patients aged 20 or older hospitalized with COP having intravenous antimicrobial therapy administration and excludes patients with a high risk for DRPs. Patients were selected into a broad-spectrum (antipseudomonal β-lactam therapy) and a narrow-spectrum (non-antipseudomonal β-lactam therapy) group based on the initial antimicrobial regimen. This study evaluates 30-day mortality as a primary outcome by inverse probability of treatment weighting (IPTW)and healthcare resource utilization as one of the secondary outcomes.

Results

A total of 15,617 patients met the inclusion criteria. This target population was divided into two groups: 2,627 patients in the broad-spectrum and 12,990 in the narrow-spectrum group. In the first group, the most commonly used antimicrobials were Piperacillin / Tazobactam (68%), and the 30-day mortality was 10.6 in contrast with 5.3% in the second group. Thus, the broad-spectrum group was associated with an increased 30-day mortality rate in contrast with the narrow-spectrum group after IPTW weighting (adjusted odds ratio 1.77, 95% confidence interval [1.52 to 2.06], < 0.001). This trend was observed regardless of pneumonia severity. The average inpatient cost was $6,139 USD for the broad-spectrum group against $5,184 USD for the narrow-spectrum group, with respective length of stay (LOS) figures of 23.1 and 19.8 days.

Conclusion

This study shows that the initial use of antipseudomonal β-lactams for COP with a low risk for DRPs is associated with higher poor outcomes, including death and higher healthcare resource utilization. Judicious selection of initial antimicrobials is warranted in the management of COP.

Disclosures

Junichi Hirayama, n/a, bioMerieux Japan: employee of bioMerieux, salary Rie Ueno, MD., BioMérieux Japan Ltd.: Employee of BioMérieux Japan Ltd. Hiroshi Mukae, M.D., Ph.D., AstraZeneca: Lecture fees|Gilead Sciences: Lecture fees|GSK: Lecture fees|MSD: Advisor/Consultant|MSD: Lecture fees|Pfizer: Lecture fees|Shionogi & Co., Ltd.: Advisor/Consultant|Shionogi & Co., Ltd.: Grant/Research Support|Shionogi & Co., Ltd.: Lecture fees
P-1541. Antimicrobial susceptibility and antimicrobial synergy testing of human Streptococcus suis isolates in Thailand
Authors: Thipmontree Wilawan , Kajeekul Rattagan , Lewrod Athita , Kerdsin Anusak , Yongkiettrakul Suganya
Published: January 2025

Background

Streptococcus suis (S. suis) infection can cause serious infections with high morbidity and mortality. Both humans and pigs have reported emerging antimicrobial resistance. This study aims to investigate the antimicrobial susceptibility test (AST) and antimicrobial synergy testing in S. suis human isolates.Table 1.Clinical manifestations of 25 culture-confirmed S. suis infection cases who performed an antimicrobial synergy test.

Methods

We conducted a retrospective study of patients with culture-confirmed S. suis infection in Northeast Thailand. We analyzed the clinical manifestations, the AST and selected 23 isolates for determining the antimicrobial synergy effect via checkerboard microdilution.Table 2:Antimicrobial synergy testing by checkerboard microdilution in 23 S. suis human isolates.

Results

Between 2021 and 2023, we included 253 culture-confirmed S. suis patients; the mortality rate was 15%. A total of 194 patients underwent echocardiograms, and 95 (48.9%) patients had infective endocarditis. The prevalence of S. suis strain resistance to penicillin increased from 7.8% in 2021 to 31.9% in 2023. Additionally, the intermediate susceptibility of S. suis to CRO/CTX rose from 3.1% in 2021 to 9.9% in 2023. Moreover, in 2023, two isolates of S. suis showed resistance to CRO/CTX.

We performed antimicrobial synergy testing in response to the surge in antimicrobial resistance of S. suis infection. The AST of 23 isolates exhibited the following: susceptible to both penicillin and ceftriaxone/cefotaxime (CRO/CTX) (3); intermediately sensitive to penicillin but sensitivity to CRO/CTX (12); intermediately sensitive to both penicillin and CRO/CTX (1); resistance to penicillin but sensitive to CRO/CTX (5); and resistance to penicillin but intermediately sensitive to CRO/CTX (2).The combination of ampicillin and ceftriaxone demonstrated synergy in 34.8% (8/23) of cases, with 65.2% showing a partial synergism effect. Penicillin and ceftriaxone showed synergy in 21.7%, partial synergy in 69.6%, and indifference in 8.7%. Conversely, the results for ampicillin-gentamicin, penicillin-gentamicin, and ceftriaxone-gentamicin showed mostly indifference: 65.2%, 73.9%, and 78.3%, respectively.

Conclusion

S. suis infection is associated with high mortality rates and increased resistance to antimicrobials. A combination therapy comprising ceftriaxone and ampicillin may be the optimal and most effective treatment option.

Disclosures

All Authors: No reported disclosures
P-1542. Determining Pseudomonas aeruginosa antibiotic resistance by leveraging methylation risk scores
Authors: Gan Shuheng , Kim Jiwoong , Kim Juyeon , Clark Andrew E , Greenberg David E , Zhan Xiaowei
Published: January 2025

Background

The increasing prevalence of antibiotic-resistant bacteria poses a significant threat to global health, necessitating innovative approaches to predict and manage resistance. Traditional methods for detecting antibiotic resistance primarily rely on phenotypic assays or short-read sequencing techniques, which often overlook the intricate epigenetic modifications that can influence bacterial behavior and resistance mechanisms. One such modification, DNA methylation, has emerged as a critical regulator in bacterial gene expression and pathogenicity. The emergence of long-read sequencing technologies offers a unique opportunity to comprehensively map methylation patterns across bacterial genomes, potentially unveiling novel insights into the mechanisms underlying antibiotic resistance.

Methods

We systematically sequenced 133

Pseudomonas aeruginosa

bacterial isolates using Oxford nanopore technology and profiled their methylation characteristics.

Results

We detected 3.38 million common methylation sites (average methylation larger than 1%, occurred in more than 10% samples). By applying methylation association analysis, we discovered 10 methylated sites that are statistically associated with resistance to 12 antibiotics. Based on these results, we developed LASSO regression models using novel weighted methylation risk scores. We benchmarked MRSs using cross validation and observed MRS prediction models have high prediction performance for phenotypic resistance to 9 antibiotics across multiple drug classes.

Conclusion

In all, this work demonstrated that long-read derived methylation can serve as a powerful predictor of antibiotic resistance, potentially transforming the field of microbial resistance research.

Disclosures

David E. Greenberg, MD, Jannsen: DSMB member|Sarepta Therapeutics: Advisor/Consultant|Shionogi: Grant/Research Support
P-1543. Clinical Characteristics and Factors Associated with Acquisition of Gram-Negative Bacteria during Ceftazidime-avibactam Therapy
Authors: Chuang Chien , Kao Tzu-Chi , Chou Sheng-Hua , Juan Chih-Han , Ho Yu-Chien , Liu Szu-Yu , Lin Yi-Tsung
Published: January 2025

Background

Ceftazidime-avibactam (CZA) is recommended to treat infections caused by carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa with difficult-to-treat resistance. The subsequent isolation of gram-negative bacteria (GNB) would cause superinfection or result in the change of antibiotics. However, the clinical characteristics and factors for acquisition of GNB during CZA treatment has not been reported.

Demographic and clinical characteristics of patients who acquired Gram-negative bacteria and those who did not acquire Gram-negative bacteria during ceftazidime-avibactam therapy

Methods

Adult patients treated with CZA ≥ 5 days were retrospectively enrolled at Taipei Veterans General Hospital (December 2019 to June 2021). We compared clinical features of patients who acquired GNB from clinical specimen 5 days after the use of CZA and those who did not acquire any GNB. Multivariate analysis was used to explore risk factors for acquisition of GNB during and 28-day mortality in patients who acquired GNB.

Distribution of acquisition of Gram-negative bacteria during ceftazidime-avibactam therapy

Results

A total of 321 patients receiving CZA for ≥ 5 days was analyzed, and 67.3% of them were infected with CRE. A total of 68 GNB were identified from the 55 patients (17.1%, 55/321). Elizabethkingia species (n=15) was the most common species, followed by Acinetobacter species (n=13) and Burkholderia cenocepacia (n=11). Diabetes mellitus [odds ratio (OR), 2.12; P=0.022], and use of mechanical ventilation (OR, 6.47; P=0.001) were the independent risk factors for acquisition of GNB in the multivariate analysis. In hospital mortality in patients who acquired GNB was higher than those who did not acquire any GNB during CZA treatment (58.2% versus 42.1%, P=0.029). More than half (63.6%, 35/55) of patients acquiring GNB were considered to have superinfection, and antibiotics were changed. Cerebrovascular disease [hazard ratio (HR), 3.27; P=0.009] and SOFA score at acquisition (HR, 1.22; P=0.001) were associated with increased 28-day mortality in patients who acquired GNB.

Conclusion

Elizabethkingia species, Acinetobacter species, and Burkholderia cenocepacia were the major GNB identified during CZA treatment, and patients who had diabetes mellitus and use of mechanical ventilation were at higher risk of acquisition of GNB. Patients who acquired GNB had higher in-hospital mortality rate. Cerebrovascular disease and disease severity were determinants of 28-day mortality.

Disclosures

All Authors: No reported disclosures
P-1581. Incidence of Cystitis and Vaginitis/Balanitis in US Veterans on Sodium/Glucose Cotransporter 2 Inhibitor Therapy for Diabetes
Authors: Lobo Zeena , Psevdos George
Published: January 2025

Background

Sodium glucose co-transporter 2 inhibitors (SGLT-2) are currently recommended for type 2 Diabetes, chronic kidney disease and atherosclerotic cardiovascular disease. Despite their known health benefits, a recent study within the Veterans Affairs (VA) Health care system found a relatively low rate of utilization for SGLT-2. Several studies have shown an association of SGLT-2 with increased risk for genital mycotic infections, cystitis and urosepsis. We evaluated the incidence of such infectious complications in US Veterans (VET)Table 1.Demographic Characteristics of the Cohort

Methods

Retrospective chart review of VET at Northport VA Medical Center who had received at least six months of SGLT-2 empagliflozin (EMP) for diabetes. VET who received EMP for heart failure only were excluded. The study years were 2018-2023. Demographic data, urinalysis, urine cultures, medical charts were reviewed for documentation of cystitis, clinical diagnosis of vaginitis/balanitis and need for hospitalization for urosepsisTable 2.Comparison of the two groups: infectious vs. no infectious complications

Results

400 VET were analyzed in the study period. The median age was 74.5 years. 78% were Caucasian, 15.5% black. 93% men. Table 1 shows the demographics of the cohort. There were 43 (10.75%) occasions of infectious complications: 32 (8%) cystitis (4 in women; one recurrent), 6 Balanitis, 5 fungal vaginitis (2 recurrent) . EMP was discontinued in all cases. 7/32 cystitis were clinical diagnoses without culture data. 6 cases of cystitis had more than 1 organism isolated. 2 VET were hospitalized due to urosepsis. There were no multidrug resistant organisms isolated (2 E. coli were resistant to ciprofloxacin) 1 case of balanitis in an HIV-infected man was cultured and grew Trichoderma atroviride. No cultures were obtained in cases of vaginitis. There were no differences in the two groups (infectious complications vs. noninfectious) in terms of age, HbA1c, BMI, GFR, duration of EMP treatment, use of insulin; However BPH was more common in the infectious group. See table 2. Table 3 lists the organisms isolated in urine cultures. No patient died from infectious complicationsTable 3.Organisms isolated in clinical specimens

Conclusion

The incidence of infectious complications in our diabetic VET due to EMP was overall low, with cystitis being at 8%, and observed more in men with prostatomegaly. E. coli was the most frequent isolate in urine cultures but no multidrug resistant organisms seen

Disclosures

All Authors: No reported disclosures
P-1588. Effect of Multiplex Polymerase Chain Reaction (PCR) versus Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MF) on Time to Optimal Therapy in Patients with Positive Blood Cultures
Authors: Baum Alexandria , Miller Jessica , Gavaghan Victoria , Argotsinger Jill
Published: January 2025

Background

Rapid diagnostic technology is an important tool that can be used to optimize antimicrobial therapy for patients with bloodstream infections Several technologies for rapid organism identification exist including matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and multiplex polymerase chain reaction (PCR). The primary objective is to compare time to optimal antimicrobial therapy with MALDI-TOF MS vs multiplex PCR rapid diagnostic systems for patients with positive blood cultures.

Methods

This multicenter, retrospective, cohort study included patients with a positive blood culture and identification via MALDI-TOF MS (June 1st – June 7th, 2021) compared to multiplex PCR (June 1st – June 7th, 2022). Patients were excluded if expired or discharged before organism identification, transferred from an outside hospital with a positive blood culture, if rapid diagnostics not performed, if identified pathogen had no defined optimal therapy per system guidelines or polymicrobial infection. The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to effective therapy (TTET), length of stay, and clinical failure defined as recurrence of bacteremia within 30 days or in-hospital mortality.

Results

A total of 221 patients were included (MALDI-TOF MS = 117; multiplex PCR = 104). Utilization of multiplex PCR compared to MALDI-TOF MS significantly reduced overall TTOT (21.1 hours vs 41.1 hours, p < 0.01). This significant reduction in TTOT with multiplex PCR was observed with gram-negative bacteremia (4 hours vs 37 hours, p < 0.01) and gram-positive bacteremia (17.8 hours vs 41.1 hours, p < 0.01) but was not statistically significant for blood cultures deemed contaminants (42 hours vs 43.5 hours, p=0.58). TTET was improved for multiplex PCR although not statistically significant (1.5 hours vs 7.5 hours, p=0.06). No differences were observed for clinical failure or hospital length of stay.

Conclusion

Multiplex PCR significantly decreased time to optimal antimicrobial therapy when compared to MALDI-TOF MS for patients with positive blood cultures.

Disclosures

All Authors: No reported disclosures
P-1595. Short Interval Repeat Testing with a Multiplex Pneumonia Panel is Low Yield- A Case for Diagnostic Stewardship
Authors: Wilber Eli , Fitts Eric , Burd Eileen , Witt Lucy S
Published: January 2025

Background

Multiplex molecular panels have emerged as a tool for the rapid identification of potential pathogens and resistance markers for multiple syndromes including pneumonia. The BioFire® FilmArray® Pneumonia panel (PPP) is a multiplex molecular test that can rapidly detect 33 targets (including bacteria, viruses, and some common resistance genes) from respiratory samples. The role of this test in patient care is evolving and the role of repeat testing is not well described.Figure 1:Results of Repeat Pneumonia Pathogen Panel within 48 Hours

Methods

We conducted a retrospective chart review of all PPPs conducted at the Emory University Hospital Clinical Microbiology Lab which supports seven academic-affiliated hospitals during the period 3/13/2023-3/14/2024. Patients with a PPP test result within 48 or 168 hours of a previous test result were identified and reviewed for interval changes in the detected targets.Figure 2:Results of Repeat Pneumonia Pathogen Panel within 168 Hours

Results

There were 2307 PPPs resulted during the study period with a numerical trend of increasing use over time. For the study period, 73 (3.2%) of tests were repeats within 48 hours and 206 (8.9%) were repeats within 168 hours of a previous PPP test. For tests repeated within 48 hours (Figure 1), 46/73 (63.0%) returned the exact same results as the initial test, 7/73 (9.6%) detected fewer pathogens, 18/73 (24.7%) detected at least one additional pathogen. 6/18 (33.3%) of tests detecting a new pathogen detected a common respiratory virus. For tests repeated within 168 hours (Figure 2), 123/206 (59.7%) returned the exact same results, 35/206 (17.0%) detected fewer pathogens, and 45/206 (22.3%) detected at least one additional pathogen.

Conclusion

Repeat testing with the PPP was common during the study period and almost nine percent of the annual testing volume was repeat testing within one week of a previous result. Short interval repeat testing with the PPP typically returns a result with no additional potential pathogens detected and thus may be unlikely to affect clinical management. Ordering restrictions that include a “lockout period” may be a valid diagnostic stewardship approach to improve the use of this test.

Disclosures

Eli Wilber, MD, Elsevier: Advisor/Consultant|Roche Diagnostics: Advisor/Consultant
P-1613. Blood Culture Contamination Mitigation: Sustained Stewardship Successes Seen Systemwide
Authors: Povroznik Mark D
Published: January 2025

Background

Contamination prevention, when sampling blood for culture, relies on an operator impeccably adhering to skin preparation routines and attentively avoiding cross-contamination opportunities until laboratory personnel attain specimen possession. Operator-reliant diagnostic integrity was challenged throughout the COVID-19 pandemic, which placed unexpected environmental pressures on personnel to the documented detriment of antimicrobial stewardship endeavors and patient outcomes. Clinician interest in shifting some operator burdens to assistive technology subsequently flared; in accordance with literature reports of successful blood culture contamination mitigation when initial-specimen diversion devices were co-opted into protocol, the National Quality Forum and the Centers for Disease Control and Prevention backed a Clinical and Laboratory Standards Institute revision to blood culture sample collection guidelines, recommending their use. This tech-centric tenet was hypothesized to be necessary to sustaining the successful mitigation of blood culture contamination through the stressor-heavy situations wherein education-focused endeavors alone were struggling to substantiate significance.

Antimicrobial Stewardship Intervention Outcome

Data reflects approximately 36,000 blood cultures drawn each quarter.

Methods

Intervention began in 2020, prior to which a 3.6% blood culture contamination rate was observed systemwide. Seventeen facilities among nineteen that share a data system co-opted initial-specimen diversion device technology alongside value analysis and cultural curation in a trifurcate strategy to reduce contamination events.

Results

Consistent, real-time communication with caretakers on outcomes enabled year-over-year interventive technology utilization increases [currently approximately 85% systemwide]. The systemwide blood culture contamination rate for the first quarter of 2024 was 1.64% [586 contamination events among 35,750 total blood cultures], down from 1.9% across 2023, 2.8% across 2022, and 3.2% across 2021.

Conclusion

Tech-facilitated closure of contaminant pathways, when paired with communication channels connecting individual contributions to stewardship successes, sustained the year-over-year systemwide reduction in blood culture contamination events observed herein.

Disclosures

All Authors: No reported disclosures
P-1617. Clinical and microbiologic outcomes associated with implementation of MALDI-TOF on patients with anerobic, fungal, and non-lactose fermenting specimens
Authors: Boda Martina , Mercuro Nicholas J , Connolly Kristina Rokas , Diekema Daniel , Yen Christina , Myatt Raymond
Published: January 2025

Background

MALDI-TOF is a rapid-diagnostic technology that improves the speed and accuracy of organism identification. Using it to identify resistant pathogens and fastidious organisms is a high impact diagnostic stewardship opportunity. This study aims to evaluate its effect on the management of infections caused by non-lactose fermenting (NLF) Gram-negative rods (GNRs), anaerobes, and yeast from sterile sites.Figure 1.Screening Process

Methods

This was a single center, quasi-experimental study of patients with NLF GNRs in respiratory specimens and anaerobes and/or yeast from sterile sites before and after the implementation of MALDI-TOF from 2021-2023. There were no changes in antimicrobial stewardship culture review or audit and feedback processes during the study period. The primary outcome was time to organism identification. Secondary endpoints were time to antimicrobial adjustment, inpatient antibiotic duration, and in-hospital mortality. Categorical descriptive data was expressed as percentages and as median/interquartile range (IQR) if continuous. Chi-squared/Fisher’s Exact test and Mann-Whitney-U were used as appropriate to compare endpoints between groups.Table 1.Patient characteristics and Secondary Endpoints by MALDI-TOF Identified Organism

Results

Of 225 patients screened, 108 were included (Figure 1). The median Charlson score was 3 (1-5). The overall length of stay was 30 (13-54) days; 75 (70%) patients had an ICU stay with a median ICU length of stay of 17 (4-31) days. The most common organisms identified were Pseudomonas aeruginosa, Bacteroides spp, Candida albicans, and Nakaseomyces glabratus (formerly C. glabrata) (Figure 2). Time from Gram-stain to organism identification was reduced from 77 (41-119) hours to 41 (26-56) hours (p< 0.001) (Table 1). Time to antimicrobial adjustment and inpatient duration of antibiotics were not different between pre- and post- implementation of MALDI-TOF for infections caused by anaerobic and NLF GNRs but was reduced in patients with yeast in sterile sites. There was no difference in in-hospital mortality.Figure 2.Percentages of Organisms Identified by MALDI-TOF

Conclusion

Implementation of MALDI-TOF for identification of these organisms improved culture processing turn-around time, antimicrobial optimization, particularly for yeast, and stewardship efforts at our institution.

Disclosures

Daniel Diekema, MD, MS, D(ABMM), Affinity Biosensors: Grant/Research Support|bioMerieux, Inc: Grant/Research Support
P-1632. Living in an area with high burden outpatient antibiotic prescriptions, a risk factor for infection by ESBL producing Enterobacterales?
Authors: Stevens Michael T , Kinsella Patrick , Campbell Darien , Ponce Rafael , Gonzalez Andrea
Published: January 2025

Background

The increase in antibiotic resistance has been linked to antibiotic exposure. However, initiatives of antibiotic stewardship programs have been associated with decrease in antibiotic utilization but without a clear decrease in antibiotic resistance. We hypothesized that patients hospitalized with infections with ESBL producing Enterobacterales (ESBL-PE) live in areas with high outpatient antibiotic exposure.

Outpatient antibiotic prescriptions per zip code

Antibiotics prescribed in the outpatient setting per zip code of residence of the recipient of the prescription.

Methods

From March 2022 to March 2023 we evaluated antibiotic utilization in the outpatient setting of a healthcare system in central Georgia. Outpatient settings included urgent cares, emergency rooms, and primary care clinics. We estimated the antibiotic “burden” per zip code based on the residence of each patient receiving a prescription from these outpatient facilities.

During the same time period, we obtained all cultures processed in the hospital’s laboratory that isolated an ESBL-PE, and the zip code of residence from each patient’s sample.

Number of antibiotics per zip code was the independent variable and number of residents per zip code hospitalized with an ESBL-PE infection was the dependent variable. QGIS v3.8 was used for spatial analysis and SPSS 25 for statistical analysis.

Number of cases of an ESBL-PE infection per zip code of patient residence

Results

There were 61 070 outpatient prescriptions, representing 500 092 days of therapy. Prescriptions were given to residents of over 1000 different zip codes of nearly 20 states. 70% (42719) of these prescriptions were for residents of the state of Georgia, distributed among 634 zip codes. The zip code with the largest antibiotic burden received 4706 prescriptions in a one-year period, representing 161 antibiotic prescriptions per 1000 population.

396 Georgia residents had a culture with an ESBL-PE, and 308 (77.7%) of them were hospitalized for infections due to ESBL-PE. Linear regression model had an R2 of 0.79 with a p-value of < 0.01.

Conclusion

The geographic reach of antibiotic prescriptions by outpatient facilities is of concern. The antibiotic burden in surrounding communities is higher than areas further away. Living in an area with high outpatient antibiotic prescription burden explained almost 80% of the variance for hospitalization with an infection due to ESBL-PE. Efforts to decrease antibiotic resistance should also include interventions in outpatient facilities.

Disclosures

All Authors: No reported disclosures
P-1637. Four-year Experience on Ambulatory Antibiotic Prescribing for Viral Respiratory Infections
Authors: Huang Joanne , Bryson-Cahn Chloe , Buck Cameron , Hori Mike , Lin David , Rizzo Tanya , Zhang Yilin , Kassamali-Escobar Zahra
Published: January 2025

Background

In 2019, our institution implemented the MITIGATE (a Multifaceted Intervention to Improve Prescribing for Acute Respiratory Infection for Adult and Children in Emergency Department and Urgent Care Settings) Toolkit, a multimodal antimicrobial stewardship strategy using education, data, and feedback to reduce unnecessary antibiotic prescribing for viral respiratory infections (RTIs) in ambulatory care settings.

Methods

This was a single center observational study. Prescribers in emergency department (ED), primary care (PC), and urgent care (UC) were notified of their individual unnecessary antibiotic prescribing from 9/2019 - 3/2022 via email. We reduced rate of feedback from notifying all prescribers, to half after the first year, and none after 2 years and observed the impact on antibiotic prescribing. Prescribers were labeled as a top performer or not a top performer compared to their peers. Unnecessary antibiotic prescribing for RTI was evaluated 4 years after the intervention began.

Results

In 2019 Pre-toolkit intervention, 14,247 patient visits had a qualifying viral RTI. 17.9%, 9.8%, and 6.4% received an antibiotic unnecessarily in the ED, PC, and UC, respectively. After 2-years of direct feedback, antibiotics were prescribed in 13.4%, 4.3% , and 4.7% , in the ED, PC, and UC (N = 48,192) (p< 0.001). In 2023, after feedback stopped, unnecessary prescribing remained lower in ED (14.4%, p< 0.001) and PC (5.8%, p< 0.001), but not UC (7.2%, p=0.015), N =53,496.

Conclusion

Rates of unnecessary antibiotic prescribing for viral RTI dropped most significantly following two years of varying degrees of direct feedback. Although prescribing rates in the ED and PC remain lower after 4 years compared to pre-intervention, current data demonstrate an uptrend. Although labor-intensive, this supports that feedback with peer comparison is an instrumental intervention. Strategies to ensure successful intervention maintenance should be considered when implementing outpatient stewardship.

Disclosures

All Authors: No reported disclosures
P-1642. The Devil's in the details: Developing metrics for discharge antibiotic stewardship
Authors: Hawkins Marten R , Prasad Ritika , Mische Leah , Esadah Esther , Mui Emily , Pourali Samaneh , Ha David R , Holubar Marisa
Published: January 2025

Background

International Classification of Diseases, Tenth Revision codes (ICD-10s) are commonly used to identify antibiotic indications but may not reflect clinician intent. We investigated concordance of different antibiotic indication sources in the electronic health record (EHR) with clinician intent upon discharge.Figure 1:Indication choices for inpatient antibiotic orders

Methods

In this quality improvement project, we included prescriptions for patients discharged on oral antibacterials from January 2022-March 2023, including patients with > 1 admission. We excluded those with >90 days duration and those for dapsone or rifaximin. We randomly selected 100 prescriptions and performed manual chart review to obtain the discharge summary antibiotic indications which we categorized into syndromes (Table 1.) We compared discharge indication with other EHR indication sources: last inpatient antibiotic order indication (is required, Figure 1), ICD-10s from separate fields ( “principle”, “encounter”, “billing”) and “composite ICD-10” which included all ICD-10s from any field. We compared each indication source with the associated discharge indication (considered most accurate) and report concordance.Table 1:Syndrome Categories and associated ICD-10 codes

Results

We included 3,088 prescriptions and excluded 364. Of the 100 encounters reviewed, 62% patients were discharged from medicine services and 46% had a trainee involved in discharge. These encounters were associated with 184 unique ICD-10s and 132 (72%) representing non-infectious diagnoses; the most common infectious diagnosis was skin and soft tissue infections (12 (7%)) (Table 2.) Overall, 37% (30/100) of prescriptions had ICD-10s that were categorized only as non-infectious. Clinicians most commonly intended discharge antibiotics for genitourinary indications (32/108, 30%) (Table 2). Last inpatient antibiotic order indication matched clinician intent in 91% of cases, while composite ICD-10 matched clinician intent in 47% of cases. Any single ICD-10 field (principle, billing, encounter) matched clinician intent in only 1/3 of cases (Table 3.)Table 2:ICD-10 codes and Clinician Intent by Syndrome

Data from 100 chart reviews. A total of 184 unique ICD-10 were collected from 100 prescriptions. 8 discharge summaries included two indications.

Conclusion

Compared to ICD-10s, last inpatient antibiotic order indication more accurately matched clinician intent for antibacterial discharge prescriptions. This may be a useful and simple way to facilitate discharge prescription stewardship.Table 3:Agreement of different indication sources from EHR with ICD-10 code

“Composite ICD-10” includes all ICD-10s from “principle”, “encounter”, “billing” fields. And was considered to match clinical intent if any ICD-10 category was concordant with clinical intent.

Disclosures

All Authors: No reported disclosures
P-1643. Simply Scripting Success: Impact of Epic Preference List Changes on Antibiotic Prescribing in the Outpatient Setting
Authors: Smith Mary , Chang Amy , Ha David R , Holubar Marisa , Shepard John , Mui Emily , Alegria William
Published: January 2025

Background

Preference lists in electronic health records are commonly used to streamline ordering processes, including antibiotic orders. In July 2023, we revised our institution's primary care preference list to align with institutional guidelines for the management of skin and soft tissue infections (SSTI) and pneumonia (Figure 1). Here we evaluate the impact of this intervention on antibiotic prescribing practices.

Methods

We included all adult telemedicine and office visits associated with antibiotic orders from 2/2023 to 2/2024 at 8 academic primary clinics. We used International Classification of Diseases, 10th revision (ICD10) data to identify encounters for SSTIs and pneumonia (Table 1 ). We defined “pre-intervention” as 2/1 – 7/31/2023 and “post-intervention” as 8/1/2023– 2/28/2024. We extracted encounter date, location, order source, antibiotic selection, and duration. We defined guideline adherence as 1st line antibiotic selection and 5-day duration (Figure 1). There were no education or dissemination efforts to providers. This was deemed a non-human subjects research quality improvement project.

Results

We included 349 total (165 pre, 184 post) encounters for SSTI (263) and pneumonia (86). 102 (29%) were telemedicine (50 pre, 52 post). Of the 349 encounters, 73 % of antibiotic orders were from the preference list (136 pre; 117 post). Guideline concordant antibiotic selection improved in the post-intervention group for pneumonia (8% pre, 44% post) and SSTIs (47% pre, 58% post), but only for orders sourced from the preference list (Table 2, Graphs 1-2). There was also improvement in guideline concordant 5-day durations with preference list orders post-intervention for pneumonia (55% pre, 78% post) and SSTI (20% pre, 50% post) (Table 2, Graphs 1-2). Antibiotic orders not using the preference list for these syndromes showed no improvement during this time.

Conclusion

We found that a simple revision of the primary care order preference list led to improved guideline concordant antibiotic prescribing for SSTI and pneumonia. For common syndromes in which antibiotic selection is typically made empirically in clinic, like SSTIs and pneumonia, pre-selected durations and highlighted first-line selections for antibiotic orders can improve adherence to guideline recommendations.

Disclosures

All Authors: No reported disclosures