bluuebunny/crossref_metadata_2025 huggingface dataset:
150. Nasal Staphylococcus aureus polymerase chain reaction (NSAP): A pediatric antibiotic stewardship tool
Authors: Marisol Fernandez , Swindle Michael , Downey Rachel
Published: November 2023

Background

In recent years, literature has flourished analyzing nasal Staphylococcus aureus polymerase chain reaction (NSAP) diagnostic performance in patients with pneumonia. Fewer data are available for other diagnoses or in pediatrics.

This study aims to determine the baseline use of NSAP results in discontinuation of anti- methicillin resistant S. aureus (MRSA) coverage in pediatric patients with bone/joint infection, complicated pneumonia, and skin and soft tissue infection (SSTI). The second aim is to calculate sensitivity and specificity of this test to help determine its utility as a tool to de-escalate antibiotic coverage.Figure 1.Inclusion and exclusionFigure 2.Anti-MRSA antibiotic use before and after negative NSAP testing

Methods

This is a single center, retrospective chart review study of patients with NSAP performed from March 2016 to September 2021. Figure 1 describes case inclusion and exclusion. Empiric antibiotic data were collected and cases were categorized according to antibiotic use with or without MRSA coverage before and directly after NSAP testing. Changes to antibiotics with regard to MRSA coverage were assumed to be related to NSAP results. NSAP results were compared to blood and other site cultures and molecular testing (if done) to determine sensitivity and specificity.

Results

Among the 135 cases included in the analysis, NSAP testing was negative for MRSA in 129 cases. Figure 2 describes MRSA coverage before and after negative NSAP results. False negative rate was < 1% (1/129).

Six cases were positive for MRSA by NSAP (4%). Empiric antibiotics for 4/6 cases provided MRSA coverage. Following positive NSAP results, MRSA coverage was initiated in 1 additional case. Cultures were congruently positive in 4/6 (67%) of these cases.

Conclusion

Institutional use of NSAP testing can result in a decrease of unnecessary anti-MRSA antibiotics. NSAP testing allowed for de-escalation of antibiotics in 40% of cases with negative results. In this sample, the false negative rate was low at < 1%, which, along with similar studies, could give precedence for a system-wide approach for deescalating antibiotics using NSAP. MRSA NSAP screening had sensitivity of 80% and specificity of 98% when compared to conventional tests.

Disclosures

All Authors: No reported disclosures
2622. Recent or concurrent rhino/enterovirus infection with respiratory syncytial virus associated with decreased symptoms and medical care use in healthy children, PREVAIL, 2017–2020
Authors: Leon Maria Deza , Gailani Adam E , Conrey Shannon C , Washington Dorcas , Burrell Allison , Teoh Zheyi , McMorrow Meredith L , Payne Daniel C , Morrow Ardythe L , Staat Mary A
Published: November 2023

Background

Respiratory syncytial virus (RSV) infections are common in children, resulting in thousands of hospitalizations each year. Viral coinfections are frequently detected during RSV infection, but the effect of these coinfections is poorly understood, and most studies only include hospitalized children. We examined the effect of the most frequently identified co-infection, rhinovirus/enterovirus (RE), on symptoms status and medical care use in a birth cohort of healthy children with RSV.

Methods

PREVAIL is a CDC-funded, 2-year birth cohort (2017–2020) in Cincinnati, OH of healthy, full-term infants. Weekly, mid-turbinate nasal swabs were tested using the Luminex Respiratory Pathogen Panel. RSV infection was defined as a swab positive for RSV (A or B). C Concurrent coinfection was defined as detection of RE at the time of RSV infection, prior RE infection was defined as a swab positive for RE up to 14 days prior to RSV infection. Symptomatic infection was defined as presence of cough or fever reported by the mother via text survey or abstracted from the child’s medical record and medical care use was defined as receiving medical care or not. Odds of symptomatic infection or medical care use with RSV were calculated using a generalized estimating equation adjusted for the child’s age at infection, type of insurance, coinfection with RE and sex.

Results

Overall, 128 RSV infections were identified in 101/245 (41%) children; 89 (69%) were symptomatic, 59 (46%) were medically attended, 4 (3%) were hospitalized. Concurrent co-infection with RE occurred in 20% (n=26) and 31% (n=40) had a RE coinfection between 0-14 days prior to the RSV episode. Coinfection with RE, whether concurrent (aOR 0.29, 95%CI 0.10-0.82) or prior (aOR 0.18, 95%CI 0.07-0.45) was associated with decreased odds of symptomatic disease. Concurrent (aOR 0.19 95%CI 0.06-0.60) or prior (aOR 0.25, 95%CI 0.11, 0.55) RE coinfection was also associated with decreased odds of medical care use.

Conclusion

RSV infections were common in the PREVAIL cohort, most infections were symptomatic with nearly half medically attended. Coinfection with RE 0-14 days prior to RSV infection was associated with decreased odds of both symptoms and medical care use.

Disclosures

Mary A. Staat, MD, MPH, CDC: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria
152. Impact of BioFire FilmArray Blood Culture Identification Panel 2 (BCID2) and Antimicrobial Stewardship Interventions on Time to Optimal Antimicrobial Therapy in Patients with Positive Blood Cultures
Authors: Nichols Isaac , Kunapuli Anjly
Published: November 2023

Background

Delayed treatment of bloodstream infections is associated with increased morbidity and mortality. Conventional methods for organism identification and susceptibility data from blood cultures can take about 2-5 days. Technological advancements in gene-based polymerase chain reaction tests amplify DNA targets from positive blood cultures and can shorten the identification time of certain organisms and resistance genes, aiding in earlier optimization of antimicrobial therapy.

Methods

This pre/post quasi-experimental, single center study was conducted 6 months prior to and 6 months after implementation of the BCID2 panel. Patients with at least 1 positive blood culture with an organism on the BCID2 panel were included in the study. One hundred twenty-five patients were included in the pre-BCID2 arm and 114 patients in the BCID2 arm. In the BCID2 panel group, real-time alerts were received by the antimicrobial stewardship team (AST) and recommendations were made to providers. The primary outcomes were time to pathogen identification, effective therapy, and optimal therapy.

Results

Demographic characteristics were similar in both groups. A higher percentage of patients with multiple risk factors for bacteremia were identified in the pre-BCID2 arm (36.8% vs 20.2%).

The mean time to pathogen identification (60 hrs vs 30 hrs; P < 0.0001) and time to optimal therapy (61.4 hrs vs 44.6 hrs; P=0.001) were shorter in the BCID2 arm compared to the pre-BCID2 arm. Patients in the BCID2 arm had an overall trend toward decreased mean time to effective therapy compared with the pre-BCID2 arm (17.5 hours vs. 14 hours; P=0.18). Subgroup analysis of blood cultures with vancomycin-resistant Enterococcus spp., ESBL-producing organisms, and Candida glabrata met statistical significance in all three primary outcomes. The BCID2 arm had a 21.9 hr. reduction in time to pathogen ID (49.6 v. 27.7; P=0.02), 38.9 hr. reduction in time to effective therapy (66.9 vs. 28; P=0.013), and a 54.5 hr. reduction in time to optimal therapy (89.3 vs 34.8; P=0.046). Overall, 99% of recommendations from the AST were accepted by providers.

Primary Outcome Results

Time to pathogen ID, Time to Effective Therapy, Time to Optimal Therapy

Secondary Outcomes 1

Total length of stay, ICU length of stay, Microbiologic Cure

Secondary Outcomes 2

30 day Mortality and Recurrent bacteremia

Conclusion

Implementation of the BCID2 panel significantly decreased time to pathogen identification and optimal therapy in patients with bacteremia.

Disclosures

All Authors: No reported disclosures
2647. A Study of Risk Factors for Severe Influenza in South India
Authors: Prasad Nidhi , Muralidhar Dantuluru , Anitha J , Acharya Chandana , KE Vandana , Surya Vamsi A , Mukhopadhyay Chiranjay , Arun Kumar G
Published: November 2023

Background

Severe influenza infections are associated with high hospitalization and increased mortality. The risk factors for severe influenza A and B are not clearly studied in the Indian population. The aim of this study was to identify risk factors in severe influenza patients who had been admitted to a tertiary care referral hospital in South India.

Methods

This was a prospective observational single center study conducted in admitted patients aged above 18 years who were confirmed to have influenza A and B by RTPCR from September 2019 to August 2021. Risk factors contributing to severe influenza were recorded. Exposure to risk factors was assessed and risk ratio/relative risk was calculated to determine strength of association. Statistical analysis was done by chi square test.

Results

A total of 285 patients were diagnosed with influenza during the study period of which 129 (45%) had severe influenza. The distribution of types of influenza amongst severe influenza cases are shown in Figure 1.

Among all subtypes chronic kidney disease (CKD) (OR-4.98), Type 2 Diabetes (OR-3.14) had statistical significance with severe influenza. The risk factor analysis for severe influenza is shown in Table 1.

On analysis of the subtypes of influenza, it was found that, CKD and Type 2 Diabetes had significant association for severe H1N1. However chronic lung disease was identified as the only risk factor for severe H3N2 infection and Influenza B infection.

The Distribution of Types of Influenza Amongst Severe Influenza Cases

Risk Factor Analysis for Severe Influenza

Conclusion

CKD, Type 2 Diabetes and Chronic lung disease are major risk factors for severe influenza infections. Given the significance of these risk factors in the Indian population, early treatment and vaccination can significantly reduce mortality and morbidity.

Disclosures

All Authors: No reported disclosures
2661. Characterization of Mpox in Southeast Michigan
Authors: Alvi Rija B R , Mann Yasmeen , Brar Simran , Brar Indira , Suleyman Geehan
Published: November 2023

Background

More than 30,000 cases of mpox have been identified in the United States. Data suggest that about 40% of affected persons are co-infected with HIV. Although most cases are self-limiting, patients with low CD4 counts are at increased risk of developing severe clinical manifestations and dying.

Methods

Retrospective case-control study comparing mpox cases among people with HIV (PWH) and HIV-uninfected persons from July to Dec 2022, at Henry Ford Health in Southeast Michigan. Demographic data, clinical characteristics, treatment, and outcomes were evaluated.

Results

54 patients were diagnosed with mpox. Overall, 42 (78%) were MSM or bisexual men, 36 (67%) Black, and 34 (63%) PWH; median age was 34.5 years (Table 1). The majority (63%) had prior sexually transmitted infections (STIs), which were more common in PWH (82% vs 30%, p< 0.001). About one-third had multiple sexual partners; more than half engaged in insertive or receptive anal intercourse. 32 (94%) of PWH were on ART, 26 (76%) had CD4 counts >200 and 19 (60%) had undetectable viral load; mean CD4 count was 602 and viral load 7942. Of the HIV-uninfected persons, 5 (25%) were on PrEP. Receipt of mpox vaccine was uncommon in either group. All patients presented with rash that was disseminated in 35%. Fever/chills, lymphadenopathy, headache, proctitis and pharyngitis were the most common manifestations and did not differ among the two groups. Concomitant STIs were present in 22 (48%) of 46 persons tested; syphilis co-infection was more prevalent among PWH (35% vs 25%, p< 0.006). Hospitalization and receipt of tecovirimat were similar between the two groups; no patients died.

Demographics, Risk Factors, Clinical Manifestations and Outcomes of Mpox Patients

Conclusion

Overall, there were no significant differences in clinical manifestations or outcomes between PWH and HIV-uninfected persons with mpox except for syphilis co-infection. Most of our PWH cohort was on ART and virally suppressed with high CD4 count. Hence, efforts should focus on rapid treatment of PWH with effective ART to achieve virological suppression and immunological recovery to minimize clinical complications and severe outcomes associated with opportunistic pathogens. Vaccinating all high-risk individuals, early mpox recognition and testing, and screening for additional STIs should be prioritized.

Disclosures

Indira Brar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria
156. Prevalence of Carbapenem Resistance Among The Clinical Isolates From Patients With Cardio Vascular Diseases Using X-pert Carba -R Real Time Multiplex PCR Assay in a Tertiary Care Hospital In Tamilnadu
Authors: Rakesh Gerard J , rohit anusha , Kumar Dorairajan Suresh , prasanthi jaya
Published: November 2023

Background

In the Post Antibiotic era with the ongoing Silent pandemic of AMR, early detection of the resistant gene exhibited by the offending pathogen causing the ailment is of paramount importance. Early diagnosis and formulating the choice of antibiotics in treatment of Multi drug and Pan drug resistant bacteria helps in reducing the hospital stay and the overall outcome of the patients.

Carbapenems serve as the first line drugs for the treatment of drug resistant Gram-negative bacilli (GNB) infections.However, carbapenem resistance (CR) among GNB is quite common in India.CR can be due to carbapenemase production.The most common carbapenemases are

bla KPC, blaNDM, blaVIM, blaIMP-1, and blaOXA-4.The present study aims to find the prevalence of Carbapenem resistance thereby aiding in initiating the empirical therapy. By studying the resistance patterns we would be able to know whether the isolate expresses single carbapenemase or multiple carbapenemases which has direct influence in the choice of antimicrobials and patient outcomes.

Methods

A total of One hundred and seventy seven clinical isolates which were Carbapenem non-susceptible Enterobacteriales, Pseudomonas aeruginosa, Acinetobater baumanii and Stenotrophomonas maltophilia isolated during the period of Jan2022- April 2023 (15 months) were included in the study. Carbapenem resistance was confirmed by Vitek 2 automated AST system.These isolates were further subjected to X-pert Carba -R Real Time Multiplex PCR Assay to detect the type of carbapenamses expressed

Results

Out of one hundred and seventy seven clinical isolates, one hundred and eight isolates did not produce carbapenemases by X-pert Carba -R Real Time Multiplex PCR Assay. A total of sixty nine isolates(38%) were positve for carbapenemases. Among the sixty nine isolates, thirty isolates(43%) produced blaNDM, fourteen isolates(20%) produced blaOXA-4.One isolate produced blaIMP-1.Twenty four isolates produced both blaNDM and blaOXA-4.

Conclusion

In Madras Medical Mission , New Delhi Metallo-Betalactamase -1 is the most common carbapenemase produced by the clinical isolates from Cardio-Vascular patients.Second most common carbapenemase is OXA-48.

Disclosures

All Authors: No reported disclosures
2691. Does Janus Kinase Inhibitor Increase the Risk of Herpes Zoster in Rheumatoid Arthritis Patients in Saudi Arabia? A Multicenter Retrospective Cohort Study
Authors: Ahmed Fida , Kaki Reham , Abudaowd Ola , Attar Suzan , Almoallim Hani , Salama Gamal
Published: November 2023

Background

JAK inhibitors (JAKi) are targeted synthetic disease-modifying antirheumatic drugs. Current evidence showed they are effective in either post Conventional or Biologic disease-modifying anti-rheumatic drugs ( cDMARDs) (bDMARDs) in patients with moderate to severe rheumatoid arthritis (RA)

JAKi could impair the immune response to viral infection by interfering with interferon signaling through JAK/STAT pathway.

Emerging Data from phase II/III clinical trials, long-term follow-up, and observational studies suggested an increased risk of viral infections, especially herpes zoster (HZ) virus reactivation in patients treated with JAKi.

Our aim was to evaluate the risk of herpes zoster in rheumatoid arthritis patients receiving JAK inhibitors.

Methods

A multicenter retrospective cohort study in Saudi Arabia. Rheumatoid arthritis patients aged 18 and above from the period of 2007-2022 were included.

Medical records were reviewed, and patients were phone interviewed to register an outcome of HZ infection.

Chi-square was used to assess the correlation between various risk factors and HZ infection.

Results

Of a total of 308 patients, 108 were on JAKi.

JAKi didn’t significantly increase the risk of HZ development (OR1.97, 95% CI 0.71- 4.67).

Patients on Etanercept had a higher risk of HZ (OR 2.88, 95% CI 1.65-2.83).

3 out of the 7 cases who developed HZ were on chronic corticosteroids. However, it wasn’t significantly associated with HZ devolvement.

Patients with Asian ethnicity were significantly more predisposed to HZ infection (OR 1.2, 95% CI 0.8-4.37).

Conclusion

In this multicenter study in Saudi Arabia, JAKi were not associated with the development of HZ among Rheumatoid Arthritis patients in real-world data.

As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain.

This finding would support the evaluation of zoster vaccination in RA patients.

Disclosures

All Authors: No reported disclosures
2694. Infectious Complications in CAR-T Cell Therapy Recipients: A Systematic Review and Meta-Analysis
Authors: Banegas Marcela , Bindal Poorva , Woodbine Maria Jose Hernandez , Aggarwal Pushan , Paredes Rodrigo , Arnason Jon , Alonso Carolyn D
Published: November 2023

Background

Chimeric antigen receptor (CAR) T-cell therapy is a rapidly evolving immunotherapy for hematological malignancies. With increasing access to this modality, there is an urgent need for a comprehensive understanding of infectious complications to optimize prophylaxis and improve clinical outcomes. We conducted a meta-analysis to assess the incidence and types of infectious complications in adult patients receiving CAR T-cell therapy.

Methods

The study was registered on PROSPERO and we searched 5 electronic databases from inception to 2022. Each author independently screened titles, reviewed full texts to identify eligible studies and extracted data from included studies using Covidence, a data extraction tool for conduction of standard systematic reviews. A random effects model was used, and proportions were used as a measure of outcome. We assessed heterogeneity using I^2 statistic. Risk of bias assessments were conducted using the RoB 2.0 for RCTs and ROBINS I tool for non-RCTs.

Results

Our search identified 12,441 studies of which 363 underwent full-text review. 33 studies were eligible for inclusion in the analysis and enrolled a total of 2866 patients. The pooled incidence of an infectious event in adult patients after CAR T-cell therapy was 38% (95%CI 0.31, 0.46; p< 0.01; I2 = 98%]. No significant difference was noted in the incidence among studies with a longer follow up duration compared to studies with follow up of ≤ 30 days [40% (95% CI 0.30-0.50) vs 32% (95% CI 0.24-0.40), p=0.20 respectively]. BCMA-directed CAR T-cell therapies used for management of multiple myeloma had a significantly higher incidence of infectious complications compared to CD19 targeted agents, 64% (95% CI 0.53-0.74, I2 = 65%) versus 39% (95% CI 0.30-0.49; I2 = 98%; p < 0.01) respectively, Figure 1. Clostridium difficile and Escherichia coli were the most common pathogens causing bacterial infections, while cytomegalovirus was the most commonly identified viral pathogen.

Figure 1.

Subgroup analysis of the pooled incidence of infectious events after CAR T-cell therapy among adult patients with hematologic malignancies

Conclusion

In this study, BCMA-directed CAR T-cell therapies were associated with a significantly higher risk of infectious complications. The results of this study can guide the development of strategies to prevent and manage infectious complications in this patient population.

Disclosures

Jon Arnason, MD, BMS: Advisor/Consultant|Regeneron: Advisor/Consultant Carolyn D. Alonso, MD, Academy for Continued Healthcare Learning: Honoraria|AiCuris: Advisor/Consultant|American Society of Healthcare Pharmacists: Honoraria|Cidara Therapeutics: Advisor/Consultant|Clinical Care Options: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support
2743. Pre-Transplant Human T-Lymphotropic Virus Screening In Allogeneic Hematopoietic Stem Cell Transplant Recipients At A Large Metropolitan Tertiary Referral Centre In Melbourne, Australia
Authors: Paykin Gabriel , Trevillyan Janine , Gador-Whyte Andrew , Garner Sarah E , Shuttleworth Peter , Trubiano Jason , Smibert Olivia
Published: November 2023

Background

Pre-transplant infectious diseases screening is an essential component of the pre-transplant workup. Many centres that offer allogeneic hematopoietic stem cell transplantation (HSCT) routinely screen for human T-lymphotropic virus (HTLV) in all recipients in the pre-transplant setting. The aim of this single centre retrospective chart review was to assess pre-transplant HTLV screening rates in allogeneic HSCT recipients at our institution in Melbourne, Australia and determine the prevalence of HTLV in this cohort.

Methods

Patients who received an allogeneic HSCT between 1st January 2018 and 31st December 2022 were identified from an institutional database. Patients who received a second HSCT during the study period were excluded from this analysis. Demographic and clinical data were extracted from electronic medical records. Descriptive analysis of the patient cohort was conducted. Data on the number and outcome of HTLV screening tests performed in this cohort between 1st January 2017 and 31st December 2022 were collated in order to determine the rate of pre-transplant HTLV screening and prevalence of HTLV in this cohort.

Results

Over the study period 116 patients received an allogeneic HSCT at our institution. Of these, 110 were included in this analysis. 67 (60.9%) were male and 43 (39.1%) were female. The mean age at time of transplant (D0) was 51.0 years. Eight (7.3%) patients received haploidentical transplants, 20 (18.2%) received matched unrelated donor transplants, 44 (40.0%) received sibling transplants and 38 (34.5%) received unrelated donor transplants. 158 pre-transplant HTLV screening tests were performed on included patients over the study period. 75 (68.2%) patients had one pre-transplant HTLV test, 25 (22.7%) had two pre-transplant HTLV tests, seven (6.4%) had three pre-transplant HTLV tests and three (2.7%) had four pre-transplant HTLV tests. All HTLV tests included in this analysis were non-reactive on enzyme immunoassay screening.

Conclusion

All patients included in this study had at least one pre-transplant HTLV screening test over the study period. There were no cases of HTLV detected in this cohort. Further research is required on the utility and cost effectiveness of routine pre-transplant HTLV screening in transplant recipients in non-endemic areas.

Disclosures

All Authors: No reported disclosures
2745. In-Vitro Activity of Cefiderocol Against Multidrug Resistant Strains of P. aeruginosa DTR, A. baumannii complex DTR, A. xylosoxidans MDR, S. maltophilia MDR & B. cepacia complex, by Iron-Depleted Broth Microdilution
Authors: Alexander Jose , Navas Daniel , Charles Angela
Published: November 2023

Background

The emergence of multidrug-resistant (MDR) & difficult-to-treat (DTR) non-fermenter (NF) organisms poses a critical challenge for antimicrobial therapy, threatening the efficacy of existing antimicrobial and contributing to an increasing worldwide mortality rate. MDR NFs are among the most challenging organisms isolated in the clinical laboratory. Cefiderocol (CFD), a novel siderophore cephalosporin, offers an interesting approach by exploiting the bacteria's iron-acquisition system and its intrinsic stability against multiple classes of β-lactamases. In this descriptive abstract, we present the in-vitro activity of cefiderocol against multiple strains of NF organisms.

Tab.1

Cefiderocol MIC distribtion for MDR non-fermenters. Dec. 2022 to April 2023

Methods

MIC values by iron-depleted broth microdilution (Liofilchem ComASP®) were collected and distributed by organism from December 2022 up to April 2023 at AdventHealth Orlando Microbiology Department. P. aeruginosa DTR (n=88), A. baumannii cpx DTR (n=38), A. xylosoxidans MDR (n=153), S. maltophilia MDR (n=84) & B. cepacia cpx (n=11). P. aeruginosa DTR is defined as an isolate intermediate (I) or resistant (R) to all tested antimicrobials except aminoglycosides. A. baumannii DTR as an isolate I or R to ampicillin/sulbactam and meropenem and one more active agent. A. xylosoxidans MDR as an isolate I or R to one agent in at least three active antimicrobial classes & S. maltophilia MDR as an isolate I or R to trimethoprim/sulfamethoxazole.

Results

The average, mode, median and range MIC (µg/mL) were calculated for each organism. P. aeruginosa DTR: 3.55, 0.25, 0.5, 0.06-128; A. baumannii DTR: 7.66, 0.5, 0.5, 0.12-128; A. xylosoxidans MDR: 3.66, 0.25, 0.25, 0.06-128; S. maltophilia MDR 0.37, 0.25, 0.25, 0.06-2; B. cepacia cpx: 11.77, 0.06, 0.06, 0.06-128.

Conclusion

Using the P. aeruginosa susceptible CLSI BP (< =4 µg/mL) as a reference for P. aeruginosa DTR, A. xylosoxidans MDR & B. cepacia cpx, 96.6%, 97.39% & 90.9% respectively have an MIC value in the susceptible BP. 76.3% of A. baumannii DTR have an MIC < =4 µg/mL (susceptible BP) and 97.6% of S. maltophilia MDR have a susceptible CLSI BP < =1 µg/mL. Although clinical outcome data is needed, cefiderocol demonstrated a significant potency against the most resistant NF strains and may represent a significant therapeutic option for difficult to treat isolates.

Disclosures

Jose Alexander, MD, D(ABMM), FCCM, CIC, SM/MB(ASCP), BCMAS, Shionogi: Advisor/Consultant|Shionogi: Honoraria
2746. Assessment of in vitro synergy between Piperacillin-Tazobactam-Meropenem and Imipenem-Meropenem against OXA-48 Producing Klebsiella pneumoniae Using Time-Kill Assays
Authors: Demir Mervenur , Aslan Abdullah Tarik , Seren Tanrıverdi Elif , Otlu Barış , Akova Murat , Paterson David , Harris Patrick N A , Hazırolan Gülşen
Published: November 2023

Background

Although double carbapenem regimens have reliable synergy against carbapenemase-producing Klebsiella pneumoniae (CP-Kp), the capacity of piperacillin-tazobactam (TZP) to provide synergistic activity with meropenem (MEM) is uncertain.

Methods

We used time-kill assays to evaluate synergy between TZP and MEM and imipenem (IMI)-MEM against non-clonal clinical CP-Kp isolates (tested by pulse-field gel electrophoresis). Five major carbapenemase genes (blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48 family) were tested by an in-house PCR. The antibiotic concentrations used in the assays were determined in two ways. First, the concentrations were selected to reflect those achievable in vivo in critically ill patients using optimal dosing strategies, i.e., 16/4 mg/L for TZP, 8 mg/L for MEM, 4 mg/L for IMI. Second, for organisms in which the MEM MIC was < 8 mg/L and IMI MIC was < 4 mg/L, the time-kill assays were performed using concentrations of carbapenems relative to the isolate’s MIC. Synergy was defined as a ≥ 2-log10-CFU/ml reductions at 24 h of exposure to the antibiotic combination compared with the single most active antibiotic, with the number of surviving organisms in the presence of the combination at > 2 log10 CFU/ml below the starting inoculum.

Results

17 OXA-48- and 3 NDM-1-producing Kp isolates were included. The combinations of TZP-MEM and IMI-MEM were synergistic against 41.2% (7/17) and 52.9% (9/17) of OXA-48 producers, respectively (Table 1, 2). The synergy between TZP and MEM (85.7%, 6/7) was relatively higher than that of IMI and MEM (71.4%, 5/7) for isolates with low MEM MIC (0.5-2 mg/L). However, the synergy was lower in TZP-MEM combination (10%, 1/10) compared to IMI-MEM combination (40%, 4/10) among isolates with MEM MIC ≥ 16 mg/L. The TZP and MEM combination was bactericidal, demonstrating a ≥ 4 log10 CFU/mL reduction at 24 h, among 35.3% (6/17) of all OXA-48 producers and 71.4% (5/7) of OXA-48 producers with low MEM MIC. In contrast, the bactericidal synergy between IMI and MEM was shown among 29.4% (5/17) of all OXA-48 producers and 28.6% (2/7) of OXA-48 producers with low MEM MIC.

There was no synergy against NDM producers for both combinations.

Conclusion

TZP-MEM combination seems to be more reliable than double-carbapenem regimens for OXA-48-producing Kp with low MEM MIC.

Disclosures

David Paterson, AMR Action Fund: Board Member|Entasis: Board Member|Merck: Board Member|Pfizer: Board Member|QPex: Board Member|Venatorx: Board Member Patrick N A Harris, PhD, DTMH, MRCP, FRACP, FRCPA, Merck: Advisor/Consultant|Opgen: Advisor/Consultant|Sandoz: Advisor/Consultant
163. Can Machine Learning Guide Antibiotic Initiation for Lower Respiratory Tract Infections?
Authors: Tang Sarah , Chang Daniel , Zhi Chin De , Piotr Chlebicki Maciej , Jasmine Chung Shimin , Wei Lee Lai , Lee Winnie , Yvonne Zhou Peijun , Kwa Andrea
Published: November 2023

Background

Accurate diagnosis of acute bacterial lower respiratory tract infections (LRTI) is often elusive. The lack of diagnostic gold standard, exacerbated by overlapping syndrome with non-infective/non-bacterial respiratory conditions, have contributed to antibiotic over-prescribing. This in turn drives drug resistance, healthcare costs and patient morbidity. We explored feasibility of developing a

classification model to identify instances where antibiotics should be initiated or withheld when bacterial LRTI is suspected.

Methods

All inpatients in Singapore General Hospital during Y2019-2020 and had ICD-10 codes for LRTI or mimicking conditions were included. Only cases with ICD-10 codes for LRTI and manually assessed to be true by the hospital antimicrobial stewardship unit (ASU) were labelled as ground truth “Yes” (i.e., antibiotics should be initiated). Cases with ICD-10 codes for other conditions were labelled as ground truth “No” (i.e., antibiotics could be withheld). Patient information (e.g., clinical notes, radiology reports, vital signs) were extracted from our hospital’s electronic data repository. Gradient boosting algorithm was applied for model building and evaluated on a 20% held-out test set. A sub-analysis on incorrect classification was also performed.

Results

There were a total of 24,399 episodes. After exclusion by ASU review and under-sampling, the ground truth “yes” and “no” groups had 2,887 and 4,888 cases respectively. The model achieved a good performance of 80% accuracy, 83% sensitivity and 79% specificity, corresponding to an AUC of 0.89. Chest imaging findings, procalcitonin, c-reactive protein, cough, neutrophil count and oxygen saturation at start of episode were the 5 most important features. Incorrect classifications had lower confidence scores, and were more likely to occur among those with severe illness or radiological reports that were not suggestive of LRTI.

Conclusion

We developed a machine learning model to support decision-making on antibiotic initiation for suspected bacterial LRTI. Further work is needed to optimise this model and evaluate its impact in clinical practice.

Disclosures

All Authors: No reported disclosures
2759. Cefiderocol vs Best Available Therapy for the Treatment of Carbapenem- Resistant Acinetobacter baumannii
Authors: Daisey Gabrielle N , Vyas Nikunj M
Published: November 2023

Background

Cefiderocol has been evaluated as a treatment of carbapenem-resistant gram negative infections. However robust data for the optimal approach to treat carbapenem-resistant Acinetobacter baumannii (CRAB) is lacking. The purpose of this study was to evaluate the efficacy of cefiderocol vs best available therapy (BAT) for the treatment CRAB infections.

Methods

This IRB-approved retrospective observational review was conducted at a three-hospital community health system between June, 2020 to February, 2021. Hospitalized patients were included if they were ≥18 years old and received ≥24 hours of targeted antibiotics for CRAB. Patients were excluded if they were considered to be colonized or were pregnant. Patients in the cefiderocol group were matched with patients in BAT group based on age and source of infection in a 1:3 ratio. The primary endpoint of this study was to assess all-cause inpatient mortality (ACIM) at the end of therapy. The secondary endpoint included clinical cure (CC) at the end of therapy. A subgroup analysis was performed for patients treated with cefiderocol monotherapy, cefiderocol combination therapy, and combination BAT to determine differences in ACIM and CC.

Results

A total of 60 patients were included in the primary analysis; 15 receiving cefiderocol and 45 receiving BAT. There was no difference in patient age, race, and diagnosis between both groups. Patients in the BAT group had a shorter length of stay vs cefiderocol group (14 vs 19 days. P=0.05). Ampicillin/sulbactam (86.7% vs 57.8%, P=0.06) and minocycline (86.7% vs 22.2%, P=0.0001) non-susceptible CRAB isolates were more common in the cefiderocol group vs BAT group (as seen in Figure 1). No differences were seen in ACIM (27% vs 18%, P=0.47) and CC (53% vs 60%, P=1.0) between both groups. The subgroup analysis revealed cefiderocol combination therapy had a decreased number of patients with ACIM and had favorable CC outcomes compared to cefiderocol monotherapy and combination BAT (as seen in Figure 2).

Comparison of Susceptibility Patterns

All Cause Inpatient Mortality and Clinical Cure in Subgroup Analysis of Monotherapy vs Combination Therapy

Conclusion

Cefiderocol seems to be a viable option for treatment of CRAB infections. No differences were seen in ACIM and CC between cefiderocol and BAT. Cefiderocol combination therapy seems to be a preferred therapeutic option for CRAB infections.

Disclosures

All Authors: No reported disclosures
2778. Retrospective evaluation of effectiveness of Flomoxef for infections due to extended-spectrum β-lactamase-producing Enterobacterales
Authors: Koizumi Ryuji , Hayakawa Kayoko , Hamada Yukihiro , Mezaki Kazuhisa , Ohmagari Norio
Published: November 2023

Background

Flomoxef (FMOX), an oxacephem, is resistant to hydrolysis by extended-spectrum β-lactamase (ESBL), and is expected to serve as a carbapenem-sparing therapy for infections caused by ESBL-producing Enterobacterales (ESBLPE). FMOX has been approved and used in Japan for the treatment of ESBLPE infections; however, data on its effectiveness and optimal dosing are limited.

Methods

This retrospective observational study was conducted at the National Center for Global Health and Medicine. We reviewed the medical records of patients with ESBLPE infections treated with FMOX for > 48 h, from 2019 to 2021. The time above the minimum inhibitory concentration (MIC) (TAM) of ESBLPE was calculated using the MIC value of FMOX for ESBLPE and the simulated FMOX concentration. Creatinine Clearance (CrCl) was calculated using the Cockcroft-Gault equation. Clinical effectiveness was defined as improvement in symptoms compared with baseline after FMOX treatment, as judged by infectious disease specialists. Microbiological effectiveness was defined as reduction of urine ESBLPE bacterial load to≤10^3 CFU/ml for urinary tract infections (UTI), or disappearance of ESBLPE for non-UTI.

Results

Fourteen patients were included in the study: 11 patients had ESBL-producing E. coli as the causative organism and nine patients had UTI. Bacteremia accounted for 35.7% of all patients. The median age of the study cohort was 81 years (interquartile range [IQR], 67.75 – 91). Nine of the patients were female.

FMOX doses varied according to the CrCl category (Table). TAM was 100% in all but one case (CrCl 48.9 mL/min, MIC of FMOX=0.5 mg/L, FMOX 1g q 12h, TAM=88.9%). Of the 13 cases for which clinical effectiveness could be assessed, FMOX was effective in nine of ten (90%) UTIs and one of three (33.3%) non-UTIs.

Microbiological effectiveness was evaluated in only two cases (UTI and pneumonia, respectively), and FMOX was microbiologically effective in both.

Characteristics of patients who received FMOX against infection caused by ESBL-producing Enterobacterales (n = 14)

Conclusion

FMOX was a clinically effective treatment for the majority of UTIs caused by ESBLPE.

For non-UTI patients, the rate of clinical effectiveness was low despite the high TAM.

FMOX is a potential carbapenem-sparing therapy for UTIs caused by ESBLPE.

Disclosures

All Authors: No reported disclosures
2783. Evaluation of Appropriate Antibiotic Prescribing Following Modification of Culture & Susceptibility Cascade for High Risk AmpC-Producing Gram-Negative Bacteria
Authors: Lim Andy , McSweeney Terrence D , Thwe Phyu , Chang Mei , Bao Hongkai , Lee Philip J , Guo Yi
Published: November 2023

Background

Updated cascade reporting of antimicrobial susceptibility (CRAS) for high-risk AmpC-producing Gram-negative organisms was implemented by the antimicrobial stewardship (ASP) and microbiology teams in June 2022 based on recent IDSA guidance. The CRAS focuses on highlighting weak inducers and poor substrate antibiotics such as cefepime and meropenem for AmpC-producing organisms: H. alvei, E. cloacae, C. freundii, K. aerogenes, and Y. enterocolitica (HECK-Yes).

Methods

A retrospective, observational, quasi-experimental study was conducted comparing the appropriateness of antimicrobials prescribed for infections with HECK-Yes organisms between pre-implementation period (July 2021-April 2022) and post-implementation period (July 2022-April 2023). Patients >18 years old with a positive blood or respiratory culture with any HECK-Yes organisms were included. The primary outcome of the study was the frequency of patients on appropriate antibiotics within 24 hours of final susceptibility report. Secondary outcomes included time to appropriate antibiotic order and administration, clinical success, microbiological failure, mortality, and reinfection/readmission within 30 days.

Results

Fifty patients were included in the pre- and post-implementation groups. Baseline characteristics were similar between the two groups (Table 1). A relative increase of 38.7% was observed in the appropriateness of antibiotics within 24 hours of final culture & susceptibility report (pre: 62% vs. post: 86%, p = 0.01). No significant difference was observed between the two groups in time to appropriate antibiotic order (pre: 4.8 hours vs. post: 3.3 hours, p = 0.37) or administration (pre: 5.9 hours vs. post: 8.0 hours, p = 0.53). There was a trend towards a lower 30-day mortality rate in the post-implementation group (pre: 24% vs. post: 14%, p = 0.10). No significant difference was observed for clinical success, microbiological failure, and reinfection/readmission within 30 days (Table 2).

Conclusion

Updating CRAS effectively increased the frequency of appropriate antibiotic prescribing for the treatment of HECK-Yes infections. The collaborative efforts of ASP and microbiology teams optimized antimicrobial prescribing for infections with HECK-Yes organisms at our institution.

Disclosures

All Authors: No reported disclosures
169. Positive blood culture after emergency department discharge of patients from a cancer center. Epidemiology, clinical features, and outcome
Authors: Alatorre Fernandez Pamela , Cardona Ortiz Alex , Islas-Muñoz Beda , Volkow-Fernández Patricia , Cornejo Juarez Patricia , Velazquez Acosta Consuelo
Published: November 2023

Background

Cancer patients frequently go to the emergency room (ER) because of fever. Within the approach, blood cultures are taken, and they are often discharged if their clinical condition is stable. The objective of the study is to know the epidemiology, clinical characteristics, and outcome of patients with positive blood cultures after discharge from the emergency department.

Methods

Between 2021 and 2022, 178 blood cultures taken in the ER were positive for infection. Of these, 93 cases (38%) corresponded to outpatients who were included. Demographic, clinical, and microbiological data were collected. A bivariate analysis comparing the cohort vs. patients that were admitted (controls) from the ER in the same period was done.

Results

Most frequent oncological diagnosis was breast cancer (21.5%), lymphoma (18.3%), and cervical cancer (11.8%). Forty-nine (53%) had recently been diagnosed with cancer, 52 (55.9%) had received chemotherapy, and 15 (16.1%) had received antibiotics within the previous month. The most frequent reasons for consultation were febrile syndrome (28%), fever after CVC manipulation (20.4%), and fever with urinary symptoms (12%). Antibiotics were prescribed on discharge from the emergency department in 57 patients (61.3%), being adequate in 36.9% of the cases. The isolate was considered to be pathogenic in 84 cases, mainly due to Gram-negative bacilli (n=58, 69%). 72 (77.4%) attended reassessment (due to telephone contact or persistence of symptoms), and 56 (60.2%) were hospitalized. The most frequent bloodstream infections were secondary (n=45, 48.4%) and catheter-related (n=33, 35.5%). Three patients died, and only in one case was it secondary to an infection, compared to 23.5% in the admitted group. The bivariate analysis is reported in Table 1.

Conclusion

Mortality in discharged patients was low (3%); Close monitoring of positive blood cultures, patient follow-up, and identification of risk factors for adverse outcomes, such as neutropenia, inflammatory response syndrome with high C-reactive protein or Procalcitonin, uncontrolled foci of infection, recent hospitalization, or antibiotic treatment should be considered for admission in this high risk population.

Disclosures

All Authors: No reported disclosures
2819. Clinical Outcomes of Fosfomycin Treatment in E. coli vs. Non-E. coli Enterobacterales Urinary Tract Infection
Authors: Traugott Kristi , Lee Grace , Groff Lindsey , Aguilar Samantha
Published: November 2023

Background

Oral fosfomycin tromethamine is considered a first-line agent for the treatment of uncomplicated acute cystitis in women according to the national Infectious Disease Society of America (IDSA) guideline. However, non-E. coli Enterobacterales urinary tract infection (UTI) pathogens exhibit higher minimum inhibitory concentrations (MICs) for fosfomycin and limited data exist to determine whether treatment outcomes are comparable to patients being treated with fosfomycin for E.coli UTIs. The objective of this study is to compare the clinical outcomes of patients being treated with fosfomycin who have E. coli UTIs compared to non-E. coli Enterobacterales UTIs.

Methods

This was a retrospective noninferiority study of adult inpatients with a UTI who received a fosfomycin inpatient from July 15, 2020 to March 15, 2023. The primary outcome was incidence of treatment failure within 30 days of start of fosfomycin, defined by retreatment for UTI; UTI related- hospitalization, urgent care visits, and/or ambulatory visits; subsequent positive blood culture; and/or infection related mortality. One-sided test for noninferiority was used with a 20% margin. Multivaraible logistic regression analyses were conducted adjusting for age/sex, UTI severity, and prior UTIs.

Results

A total of 77 patients were included; 45 with E. coli UTIs and 32 with non-E. coli Enterobacterales UTIs. The majority of the patients were female (80.5%), with a median age of 67 years (IQR, 61-69), Hispanic/Latino (50.6%), had chronic kidney disease (33%), and diabetes mellitus (35%), and were admitted to a non-ICU floor (79%). The overall incidence of treatment failure was 19.5% (90% CI 12.9%-27.7%); 15.6% in those with E. coli vs. 25% in those with non-E. coli Enterobacterales UTIs (p=0.385; absolute difference 9.4%; 90% CI -7.3% to 26.2%), not meeting the criteria for non-inferiority. In multivariable analysis, E. coli vs. non-E. coli Enterobacterales UTIs did not associate with treatment failure (adjusted odds ratio, 0.66; 95% CI 0.193-2.25; p=0.505).

Conclusion

Fosfomycin treatment for non-E. coli Enterobacterales UTIs did not meet non-inferiority criteria when compared to patients with E. coli UTIs. Further studies with larger sample sizes are required.

Disclosures

All Authors: No reported disclosures
183. Combination Antibiotic Therapy vs Monotherapy for Methicillin Resistant Staphylococcus aureus Endocarditis
Authors: Crosby James M , Jo Stoner Bobbi , Cremeans Kelli , El-Dalati Sami
Published: November 2023

Background

Mortality for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis remains unacceptably high. It is unclear whether combination antibiotic therapy results in improved clinical outcomes, which antimicrobials are most efficacious and when to initiate a combination regimen. We retrospectively evaluated patients over 1-year with MRSA endocarditis who were treated with either monotherapy with vancomycin or daptomycin or combination therapy with daptomycin and ceftaroline (D/C) or vancomycin and ceftaroline (V/C).

Methods

Patient cases were identified from the University of Kentucky’s endocarditis team (Figure 1). Demographic variables and clinical outcomes data were collected and reviewed by 2 investigators. Data analysis was conducted using Chi-Square tests and one-way ANOVA assessments. The primary outcome was in-hospital mortality. Secondary outcomes included: time to blood culture clearance and 90-day mortality.

Results

Between September 7th, 2021 and September 6th, 2022 we identified 49 patients with MRSA endocarditis treated with the designated regimens. There were no significant demographic differences between the study groups (Table 1). Twelve patients were treated with monotherapy, 23 patients were treated with D/C and 14 patients were treated with V/C. In-hospital mortality was 8.3% in the monotherapy group, 11.6% in the V/C group and 17.4% in the D/C group (p=0.60; Table 2). Average time to initiating combination therapy was after 4.7 days of bacteremia in the V/C group and 5.2 days in the D/C group (p=0.55). Average duration of bacteremia was 4.3 days in the monotherapy arm. Patients who received D/C cleared blood cultures after 3 days of combination therapy compared to 4.3 days in the V/C group (p=0.26). Receipt of D/C within 72 hours of the first positive blood cultures was associated with the lowest in-hospital and 90-day mortality across all groups, but this was not statistically significant (Table 3).

Conclusion

There was no significant difference in in-hospital or 90-day mortality between patients treated with monotherapy, D/C or V/C. Further studies of larger populations are required to identify which treatment approach results in the best clinical outcomes for patients with MRSA endocarditis.

Disclosures

All Authors: No reported disclosures