bluuebunny/crossref_metadata_2025 huggingface dataset:
2807. Using Less of Our Big Guns: Vancomycin De-Escalation Using Methicillin-Resistant Staphylococcus aureus Nasal Swab Screening Protocol
Authors: Sittirat Petchpailin D , Choi Sarah J , Cain Daniel , Pradeep Sidart , Jain Alisha M , Bommisetty Nikitha , Kalluri Sneha , Youree Bryan , Ramarathnam Vivek , Abbasi Jamil A , Bastidas Alexander , Myers Rick , Rao Sunaina , Yarger Theresa , Smith Sommer , Carr Adrienne , Gautam Shovendra
Published: November 2023

Background

Empiric parenteral vancomycin is crucial to early sepsis treatment due to its efficacy against organisms resistant to other antibiotics, including Methicillin-resistant Staphylococcus aureus (MRSA). Reliance on broad spectrum antibiotics has contributed to antibiotic resistant organisms and nearly 5 million deaths in 2019 [1]. The goal of this study was to improve antibiotic stewardship by using MRSA nasal swab screening to expedite parenteral vancomycin discontinuation. Total hospital and ICU length of stay, sepsis and severe sepsis incidence, Clostridium difficile incidence rates and institutional vancomycin usage were also measured.

Methods

This project is a retrospective observational study on patients admitted to the ICU and placed on parenteral vancomycin over a 31-month period. Using the classic Plan-Do-Study-Act cycle, a standing antibiotic de-escalation protocol (the “Protocol”) was created which called for a pharmacist to order a nasal MRSA swab on the patient within 48 hours of vancomycin initiation. The critical care team used these results to decide whether to continue vancomycin.

Results

91/93 patients studied received MRSA nasal swabs. The average hospital stay was 12 days and average ICU stay was 5.6 days. The average vancomycin usage was 5.5 +/- 4.2 days, with discontinuation within 5.1 +/- 4 days of a negative MRSA swab, depending on the infection source. 2/93 (2.2%) restarted vancomycin. The average vancomycin usage (Monthly Days of Treatment/1000) prior to Protocol initiation was 79.63 and decreased to 67.17 with Protocol implementation. There was no significant impact on incidence of sepsis or Clostridium difficile infections.

Process metrics

+Average days from MRSA nasal swab result to vancomycin discontinuation by suspected primary site of infection.

Outcome metrics

Study protocol was initiated in March 2020. Sepsis and severe sepsis rates were between the months of January 2016 to October 2022. C. difficile infection rate data was taken from January 2016 to December 2022.

Conclusion

The primary goal of decreasing vancomycin usage with early MRSA nasal swab screening was successful. Standardized reevaluation of vancomycin usage after obtaining MRSA swab results led to discontinuation of vancomycin in 30/91 patients (32.9%) with 2/91 (2.2%) being restarted during the same admission. A linear regression model was applied to this data and supported our results. There was no significant impact on length of stay related to sepsis, or incidence of hospital acquired Clostridium difficile infection. Further study is warranted to see how the Protocol impacts these areas.

Disclosures

All Authors: No reported disclosures
2810. A synergy test to assess the activity of the Ceftazidime-Avibactam and Aztreonam combination: An experience from a single centre in Malaysia
Authors: Nee Tang Soo , Shuan Cindy Teh , Nurliyana Wan , Karunakan Rina , Sulaiman Helmi
Published: November 2023

Background

Southeast Asia has a high prevalence of metallo-β-lactamase-producing carbapenem-resistant Enterobacterales (CRE). Ceftazidime-avibactam (CZA) and Aztreonam (ATM) combination is one of the preferred therapeutic options against them.

Methods

A prospective study was performed at a university hospital in Kuala Lumpur, Malaysia, involving CRE isolates resistant to CZA and ATM. Susceptibility testing results were interpreted using the Clinical and Laboratory Standards Institute (CLSI) breakpoints. A synergy test for both agents [as in Falcone et al. study (CID 2021:72)] was carried out using the double disk synergy (DDS) and the gradient test superposition (GTS) methods. Synergy was considered present when the inhibition zone between the two disks became evident and if CZA reduced the ATM minimum inhibitory concentration (MIC) below its CLSI susceptibility cut-off (≤4 mg/L).

Results

Eleven isolates (8 K. pneumoniae, 2 E. coli, and 1 K. aerogenes) from 10 patients were tested. Concordant results were seen for both methods for all the isolates. Synergy was demonstrated with 8 isolates; for 2 of the 3 isolates with no synergy, the MIC of ATM reduced to an intermediate result after GTS. The most common sites of infection were bloodstream infection (4) and intra-abdominal infection (3). Five patients received the CZA-ATM combination (one received two courses of CZA-ATM). Five isolates from four patients demonstrated synergy, and one showed intermediate synergy. The latter received additional IV tigecycline. The median time to CZA-ATM initiation from the index culture was 8 (3-13) days. The median duration of therapy was 21 (6-28) days. Four patients responded favorably to the agents (survived the infection), while the remaining patient died. For those that did not receive CZA-ATM, one received polymyxin-based therapy, one received high-dose, extended-infusion meropenem, and one received no treatment. Only the patient that received meropenem survived the infection. Please refer to Table 1.0 for more detail.

Conclusion

Based on this small sample size, only a 73% synergy rate between CZA and ATM was seen for our CRE isolates resistant to CZA and ATM. Favorable treatment response was seen in those receiving the CZA-ATM combination therapy when synergy was demonstrated

Disclosures

All Authors: No reported disclosures
2834. Comparative Effectiveness of Oral Antibiotics to Treat Urinary Tract Infections in Male and Female Outpatients
Authors: Madaras-Kelly Karl , Boyd Jeremy , Bond Laura
Published: November 2023

Background

Professional and regulatory agency guidelines recommend that fluoroquinolones not be used as first-line therapy to treat uncomplicated UTI. Increasingly, β-lactams are being used to treat UTI despite limited evidence supporting their effectiveness. The study aim was to compare the efficacy of β-lactams and other commonly prescribed antibiotics for UTI to fluoroquinolones.

Methods

A multi-centered retrospective cohort study of outpatient visits with a UTI diagnosis between 2019-2021 was developed. Inclusion criteria: In-person visit in the Emergency Department or Primary/Urgent Care with ICD-10 documented UTI diagnosis and oral antibiotic prescription filled within 0-2 d. Exclusion criteria: Prior UTI < 30d, co-diagnosis where antibiotics were indicated, hospital discharge < 7d, scheduled urological procedure < 7d, pregnancy. Outcome: UTI related admission or outpatient return visit within 3-30d. Demographic, co-morbidity, vitals, laboratory, and prescription data were extracted. Propensity scores were used to balance treatments and GEE models were used to estimate outcomes.

Results

There were 73,334 visits in 130 VA medical centers. Mean (S.D.) cohort age was 66.0 (15.8) y, 22.9% were female. Antibiotics prescribed N (%): β-lactams (cephalosporins, aminopenicillins) 27,385 (37.3%), nitrofurantoin 15,509 (21.1%), trimethoprim / sulfamethoxazole (TMP/SMX) 15,453 (21.1%), and fluoroquinolones 14,997 (20.4%). The overall 30-day clinical failure rate was 10,525 (14.4%).

Comparative Effectiveness of Oral Antibiotics for Outpatient UTIs

Conclusion

Commonly prescribed antibiotics for outpatient UTI were associated with a modest increase in 30-day clinical failure relative to fluoroquinolones. Effectiveness differences were most pronounced in male patients. Clinicians should carefully differentiate between complicated and uncomplicated UTI in males and consider preferentially prescribing fluoroquinolones.

Disclosures

Karl Madaras-Kelly, PharmD, MPH, BioMerioux: Grant/Research Support
2847. Healthcare utilization among older adults hospitalized with complicated urinary tract infections in the United States
Authors: Zhang Helen L , Ohnuma Tetsu , Spellman Alexandria A , Raghunathan Karthik , Krishnamoorthy Vijay , Anderson Deverick J , Schmader Kenneth E , Scales Charles , Advani Sonali
Published: November 2023

Background

Healthcare utilization for complicated urinary tract infections (cUTI) is increasing in recent years, especially among older adults due to comorbidities and immunosuppression. However, healthcare utilization and inpatient antibiotic use for cUTI are poorly described among older adults.

Methods

This retrospective cohort study included inpatients aged ≥18 years with cUTI identified using ICD-10 diagnostic codes who were discharged alive from 240 hospitals in the Premier Healthcare Database (January 2016 – June 2020). Sociodemographic factors, clinical characteristics, antibiotic use, and healthcare utilization measures were stratified into 2 age groups: adults 65 years and older (“older adults”), and adults under 65 years (“younger adults”). Bivariate comparisons were performed using chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables.

Results

Among 14,981 patients, 8,073 (53.9%) were ≥65 years. Compared to younger adults, older adults with cUTI were more likely to be male (54.5% vs. 38.1%, p < 0.001), be in an intensive care unit (70.4% vs. 65.7%, p < 0.001), and receive vasopressors (26.6% vs. 23.1%, p < 0.001). Older adults with cUTI had a longer median length of stay (8 vs. 7 days, p < 0.001), were more likely to be discharged to nursing homes (40.7% vs. 18.2%, p < 0.001), and had a higher median cost of hospitalization ($18,191.62 vs. $15,800.76, p < 0.001). Older adults also received higher median days of antibiotic therapy (11 vs. 10 days, p = 0.009) and were more likely to receive intravenous (IV) vancomycin (54.9% vs. 51.7%, p < 0.001) or cefepime (31.2% vs. 28.0%, p < 0.001) though less likely to receive an aminoglycoside (9.5% vs. 12.1%, p < 0.001) (Table 1).

Conclusion

Older adults hospitalized with cUTI required higher acuity of care and more post-acute institutional care, and they incurred higher healthcare costs than younger adults. Older adults also had different antimicrobial utilization patterns, including more frequent use of IV vancomycin or cefepime. Future studies should evaluate post-discharge healthcare utilization and antimicrobial use among older adults with cUTI.

Disclosures

Charles Scales, MD MSHS, BMS: Grant/Research Support|Exelixis: Grant/Research Support|Flume Catheter: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support Sonali Advani, MBBS, MPH, FIDSA, bioMérieux: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant
1937. Use of Paxlovid for Treatment of Acute COVID-19 and Occurrence of Post-COVID Conditions among Children and Adults at High-Risk for Severe COVID-19, April 1 - December 31, 2022
Authors: Dalton Alexandra F , Baca Sarah , Raykin Julia , Perrine Cria , Boehmer Tegan , Koumans Emilia , Patel Priti , Saydah Sharon
Published: November 2023

Background

Data have suggested that treatment with Paxlovid for acute COVID-19 decreases the incidence of Post-COVID Conditions (PCC); however, results are limited to specific age groups and populations. This analysis assessed the occurrence of PCC following receipt of Paxlovid among children and adults at risk for severe COVID-19.

Methods

Patients aged ≥ 12 years with COVID-19 (defined by ICD-10 code, positive SARS-CoV-2 test, or Paxlovid prescription) and at increased risk for severe COVID-19 due to age, underlying conditions, or immune-suppressing medications, were identified in HealthVerity claims data. Eligible persons had an outpatient, telehealth, or emergency department encounter for COVID-19 between April 1 – August 31, 2022. Exclusions included liver disease, end-stage renal disease, a prescription for contraindicated medications, pregnancy in the previous year, or death within 60 days. Case patients received a Paxlovid prescription within ±5 days of the index date; control patients matched on age, sex, month, and region did not receive Paxlovid within ±5 days. Cases and controls were matched 1:2. Analysis was conducted separately for 3 age groups: 12-17 years, 18-49 years, and ≥50 years. PCC was defined as new conditions > 60 days after index date and prior to December 31, 2022. We calculated the relative risk (RR) of two overall PCC indicators (≥ 1 or ≥ 2 conditions) and 45 individual conditions.

Results

Among adults aged ≥ 50 years, the risks of overall and individual PCCs were generally lower among case- than control patients (RR for ≥1 condition=0.92, 95% CI=0.91-0.93; Figure 1). There was no overall difference in risk among adults 18-49; the RR of individual conditions varied (Figure 2). Among adolescents, the risks of overall and individual PCCs were higher among case than control patients (RR for ≥1 condition=1.07, 95% CI=1.02-1.12; Figure 3).Figure 1.Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages ≥50 (N=564,303)Figure 2.Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages 18-49 (N=292,818)Figure 3.Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages 12-17 (N=17,178)

Conclusion

The results suggest that Paxlovid helps reduce occurrence of PCC in adults aged ≥ 50 years. Among younger adults and adolescents, associations were observed for only certain conditions. This may be due to a difference in baseline health in these age groups. Further investigation may help clarify whether Paxlovid provides benefits in reducing PCC in addition to severity of acute COVID-19.

Disclosures

Priti Patel, MD, MPH, Pfizer: Stocks/Bonds
192. Characteristics of Staphylococcus aureus Bacteremia in Patients With Substance Use at a Large Academic Safety-Net Hospital 2020-2021
Authors: Gomez Christian , Sopirala Madhuri , Kambhampati Aparna
Published: November 2023

Background

Staphylococcus aureus bacteremia is a serious infection with a high mortality rate. Substance use disorder has been identified as a risk factor and poses unique challenges for treatment and outpatient parenteral antibiotic therapy (OPAT) eligibility. Outcomes of in this patient population have not been well studied. To address this gap, we conducted a retrospective study to evaluate the outcomes of patients with substance use disorder admitted with S.aureus bacteremia.

Methods

We conducted a retrospective epidemiological study of adults with substance use within 1 year and admitted to Parkland Hospital from April 2020 to March 2021 with diagnosis of S. aureus bacteremia during admission. Clinical and epidemiological data was collected using the electronic medical records system.

Results

68 patients met inclusion criteria. 35 patients (52.4 %) reported active Intravenous drug use (IV). Cocaine use was reported by 40 %, Opioid use by 65.7 %, and amphetamine use by 26.9% of patients. 46% of patients were homeless and 52% were uninsured. Initial sources of bacteremia included skin and soft tissue infections (34%), bone and joint infections (31%), and infective endocarditis (22%). Most patients (40%) were discharged to a facility, while 24% were discharged home and 24% left against medical advice.

Readmission within 30 days was observed in 21% of patients. Mortality at 30 days was 4.5%, while mortality at 1 year was 12%, with 17 patients (25%) lost to follow-up. Infectious complications related to S. aureus bacteremia within 1 year were seen in 31% of patients, with SSTI being the most common complication (16.4%). Six patients (9%) were diagnosed with endocarditis in a subsequent encounter. Leaving against medical advice was associated with an increased risk of S. aureus related complications after discharge (OR 6.6, 1.69-25 P=0.006)

Conclusion

There is significant burden of S. aureus bacteremia in patients with substance use disorder. Findings also suggest that infectious complications related to S. aureus bacteremia after discharge are common and require close monitoring and timely intervention. There is need for continued research to better understand the outcomes of patients with substance use disorder and to identify strategies for improving care

Disclosures

All Authors: No reported disclosures
225. Dalbavancin Usage in Patients Who Inject Drugs (PWID)
Authors: Patel Kaya , Nakagami Peter , Morita Kazumi , Gallagher Jason , Schultz Sara K
Published: November 2023

Background

Dalbavancin is a lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI) secondary to gram-positive organisms. Given its long half-life, there has been increasing off-label use for other indications: osteomyelitis, joint infections, and bacteremia. One application where it can be effective is in PWID due to high rates of incomplete IV therapy. Herein we describe characteristics of PWID patients that receive dalbavancin and outcomes including recurrence of infection.

Methods

We conducted a retrospective chart review of all patients receiving dalbavancin at our large academic medical center in Philadelphia between Nov 1, 2019, to October 31, 2022. Charts were reviewed in Epic with data collection in REDCap.

Results

Fifty-two patients with substance use disorder with injection behavior that received dalbavancin were reviewed. Forty-seven (90%) of these patients had unstable housing. Patients were recommended dalbavancin due to concerns for adherence to prolonged oral regimen (31, 60%) or to avoid lengthy hospitalization which did not align with patient’s goals of care (43, 83%). Patient directed discharges occurred in 20 (38%) patients. Indications included bone/joint infections (25, 48%), bone/joint infections involving prosthesis (3, 6%), bacteremia (9, 17%), endocarditis (3, 6%) and ABSSSI (24, 46%). Twenty-one (40%) patients who received dalbavancin avoided a full IV antibiotic course. Forty-eight (92%) patients received effective antibiotics prior to dalbavancin (average of 6.2 days). Forty-three (83%) patients received a full dalbavancin course, of which 2 (5%) patients were readmitted for relapsed infection in 90 days. Nine (17%) patients received partial dalbavancin treatment courses, of which 6 (66%) had 90-day readmissions for relapsed infection. (Table 1).

Conclusion

At our institution, dalbavancin was used to treat infections beyond ABSSSI, in a population of predominantly PWID. We show low rates of 90-day readmission for recurrent infection, including patients with bacteremia and endocarditis, following full courses of dalbavancin. Dalbavancin is a viable alternative to lengthy oral or IV antibiotic regimens in patients that would otherwise not receive full treatment courses.

Disclosures

Jason Gallagher, PharmD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant Sara K. Schultz, MD FACP FIDSA, AbbVie: Advisor/Consultant
226. Low incidence of Pseudomonas species in Gram negative blood stream infections in nine hospitals across Ecuador: an unexpected find
Authors: Zurita Jeannete , Sevillano Gabriela , Belen Solis Maria , Paz y Miño Ariane , Rizkallah Alves Beatriz , Zurita-Salinas Camilo , Bacteremia Ecuadorian
Published: November 2023

Background

Over the last years, several studies on bloodstream infections (BSI) have ranked P. aeruginosa in the top 5 list of Gram-negative causal agents. However, there is very limited data regarding the incidence of Pseudomonas bacteremia in Latin America. The aim of this study was to establish the incidence of bacteremia caused by Pseudomonas species

Methods

During the period from November 2021 to May 2022 in 9 hospitals in Ecuador, blood culture samples were taken according to the clinical requirements of each patient. The bacteria identification was carried out using automated system (Vitek2 and Phoenix1000) and was confirmed by proteomic (MALDITOF) and molecular sequencing. Antimicrobial susceptibility was performed according to CLSI 2021.

Results

A total of 297 gram-negative bacilli BSI were identified across the 9 hospitals where the study took place. Blood cultures positive for Pseudomonas spp. represented just 0.043% (13/297) of all bacteremia (Table 1). Four of the thirteen Pseudomonas presented a MDR profile. Resistance to carbapenems was higher than that observed in antipseudomonal cephalosporins (Table 2). P. aeruginosa species was the most prevalent variant (9/13) 69.2%, however other species such as P. stutzeri, P. libanensis, P. mosselii, and P. otitidis were also identified. It is important to emphasize that automated system failed to recognize these species. These four Pseudomonas species have not been reported before in Ecuadorian hospitals, most likely because in many hospitals MALDITOF and genomics are not routinely performed. The population demographic profile is shown in Table 3. Among the 13 patients with confirmed Pseudomonas spp. BSI, presumed bacteremia source varied among the samples.

Conclusion

This study provided relevant information on BSI caused by Pseudomonas in Ecuador.There are only few population-based studies evaluating bacteremia epidemiology in Latin America. SENTRY in 1997 estimated that P. aeruginosa contributed to 10.6% of gram-negative nosocomial and community-acquired bloodstream infections. Lower incidence levels, as seen in this study (0.043%), could help better understand population trends and help guide treatment.

Disclosures

Jeannete Zurita, n/a, Pfizer: Grant/Research Support
233. All Clostridium butyricum strains isolated from blood cultures were derived from probiotics: a single-centre retrospective study
Authors: Sada Ryuichi M , Motooka Daisuke , Kutsuna Satoshi , Hamaguchi Shigeto , Yamamoto Go , Ueda Akiko
Published: November 2023

Background

Clostridium butyricum

(C. butyricum) is a strictly anaerobic, Gram-positive, spore-forming bacillus named for its capacity to produce high amounts of butyric acid. Some strains of C. butyricum involved in infectious diseases are known to be currently used as probiotics in Asia. Especially in Japan, MIYA-BM® is one of the probiotics commonly used as prescription drugs and it contains C. butyricum MIYAIRI 588 strain (CBM588). On the other hand, other strains involved in infectious diseases are known to be pathogenic. Bacteremia due to C. butyricum is a rare condition, and the prevalence, clinical features, and bacteriological and genetic origins of the condition are unknown.

Methods

We conducted a retrospective cohort study of medical records of patients to detect cases of C. butyricum bacteremia in Osaka University Hospital from September 19, 2011, to February 5, 2023. We analyzed the whole-genome sequencing of C. butyricum strains from positive blood culture samples, as well as strains from the probiotic MIYA-BM®. We also analyzed to determine the homology between these strains.

Results

Out of a total of 6576 positive blood culture samples, we detected five cases (0.08%) of bacteremia due to C. butyricum. Whole-genome analysis showed that the genes of each strain had only 1-33 mutations compared to the genes of the CBM588 strain, identifying them as the same clone derived from MIYA-BM®. The detail of case characteristics is shown in Table 1. All patients had bacteremia during hospitalization, with two male and three female patients. Four patients had concurrent use of MIYA-BM®. Four patients had immunocompromised conditions, and two patients had end-stage kidney disease on dialysis. All patients had a fever and abdominal symptoms such as diarrhea and pain. A patient with non-occlusive mesenteric ischemia died within 90 days.Table.Detailed clinical and microbiological information on five cases.

Conclusion

All C. butyricum strains detected from blood cultures in our hospital were derived from probiotics. Although C. butyricum bacteremia is rare condition, the use of MIYA-BM® use in hospitalized patients with multiple medical interventions is considered to cause C. butyricum bacteremia.

Disclosures

All Authors: No reported disclosures
238. Comparison of Outcomes of Patients with Gram-Negative Bacterial Left Ventricular Assist Device-Related Infections on Chronic Suppressive Antibiotic Therapy versus Patients Monitored on No Antibiotic Therapy
Authors: Svoronos Petros , Marschalk Nicholas , Sarwar Sajed , Lampert Brent , Nichols Courtney
Published: November 2023

Background

Left ventricular assist devices (LVAD) are used for short- and long-term support in heart failure. LVAD-related infections may manifest as infections of the driveline or bacteremia and may result in morbidity and mortality. Treatment may involve surgical debridement and prolonged antimicrobial therapy. Given concern for recurrent infection due to retained hardware, suppressive antibiotics are commonly utilized after the index infection. However, minimal data is available to guide these decisions.

Methods

This was a single-center, retrospective cohort study at our institution from November 1, 2011 to September 1, 2021 comparing outcomes after index LVAD-related gram negative driveline infections or bacteremia who received suppressive antibiotic therapy versus those who did not. Patients on suppressive antibiotics for previous gram-positive infections were excluded. Fischer’s exact test was used to evaluate for statistically significant differences between the two groups.

Results

Of 460 patients who underwent LVAD placement, 32 patients met inclusion criteria. Demographic data and infection related outcomes are summarized in Tables 1 and 2. Number of infection recurrence (61.5% vs 57.9%) and LVAD-related infection re-admissions (69.2% vs 73.7%) were similar between the two groups. A higher proportion of patients started on chronic suppressive therapy during the index infection had surgical management (53.8% vs 36.8%) and bacteremia as their index infection (30.8% vs 18.8%). Subsequent cultures positive for multidrug resistant (MDR) organisms (15.4% vs 10.5%) and infection-related mortality (15.4% vs 0%) were also both observed to be higher in the group on chronic suppressive antibiotics. No statistically significant difference was observed in outcomes between the two groups (Table 2).

Conclusion

Following index gram-negative LVAD-related infections, patients transitioned to suppressive antibiotic therapy were observed to have similar outcomes compared to those monitored off chronic antibiotic therapy at our institution. Future studies with a larger sample size are necessary to determine if there is a statistically significant benefit to suppressive antibiotic therapy after gram-negative LVAD-related infections.

Disclosures

All Authors: No reported disclosures
275. Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli
Authors: Hwang Munok , Choi Hosoon , Navarathna Thanuri , Boykin Katherine , Corona Brandon , Dhar Sorabh , Donskey Curtis , Cadnum Jennifer , Chatterjee Piyali , Kaye Keith S , Jinadatha Chetan
Published: November 2023

Background

Most Escherichia coli reside as commensal intestinal microflora without harming human health. But some E. coli strains are pathogenic and can cause deadly infections. Antimicrobial resistant E. coli is associated with more than 1.5 million deaths globally. Here, we studied the prevalence of antimicrobial resistance in E. coli isolates from two cities based on the antimicrobial(AMR) genes and MIC values. By correlating genotypic and phenotypic antimicrobial resistance, we also examined the performance of whole genome sequencing (WGS) based prediction of phenotypic resistance.

Methods

A total 109 E. coli isolates from Detroit, MI and Cleveland, OH hospitals underwent WGS. Antibiotic susceptibility testing (AST) was performed using the gram-negative AST cards on the VITEK 2 system. WGS was performed with Nextseq 550 using Nextera flex kits. After de novo assembly, AMR genes were identified using AMR gene database, ResFinder.

Results

The resistance to beta-lactam antibiotics including 1st and 3rd generation cephalosporins were very high among the E. coli isolates. They were susceptible to penicillin combinations and 2nd generation cephalosporins. While resistance to quinolone antibiotics was high, resistance to aminoglycoside, tetracycline, and sulfonamide/trimethoprim were relatively low (Figure 1). As shown in Table 1, WGS-based method accurately predicted the majority of antimicrobial resistance phenotypes with accuracy of 0.89 ∼ 1.0. However, for cephalothin (0.36), piperacillin/tazobactam (0.69), and amikacin (0.63), the prediction accuracy was low which could potentially lead to false predictions of antimicrobial resistance. Extended Spectrum Beta-Lactamase (ESBL) genes such as blaCTX-M, blaOXA, and blaTEM were abundant, though subtle difference in the prevalence of AMR genes between two cities was observed (Figure 2).Figure 1.The prevalence of antimicrobial resistance to various antibiotics in E. coli isolates from Detroit, MI and Cleveland, OH.Figure 2.Prevalence of WGS identified AMR genes associated with antibiotics drugs.

Conclusion

Most of the E. coli isolates contained various ESBL genes and their gyrA genes were mutated to quinolone resistant forms. Therefore, most of the isolates were resistant to many beta-lactam and quinolone drugs. WGS based prediction of phenotypic resistance showed good predictive values but needs more studies to increase sensitivity and specificity.

Disclosures

Keith S. Kaye, MD, MPH, Abbvie: Advisor/Consultant|Abbvie: Honoraria|Entasis: Advisor/Consultant|Entasis: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|VenatoRx: Advisor/Consultant|VenatoRx: Honoraria
297. Prevalence and Genomic Analysis of Hypermucoviscous Klebsiella pneumoniae in a Single Center in Japan: Insights into Virulence and Potential Clinical Implications
Authors: Nishiyama Naoya , Arakaki Wakako , Uechi Kohei , Utsumi Daisuke , Sato Yukuto , Nakamatsu Masashi , Kinjo Takeshi , Yamamoto Kazuko
Published: November 2023

Background

Hypervirulent Klebsiella pneumoniae (hvKp) is associated with severe clinical outcomes, including liver abscesses and disseminated infections (Fig 1). The hypermucoviscosity phenotype (HMV), confirmed by the String test, has been linked to hvKP. This study aimed to investigate the prevalence and genomic characteristics of HMV-Kp isolates in patients with K. pneumoniae bacteremia in a single medical center in Japan.Figure 1.The case of endophthalmitis and multiple abscesses by hypermucovisucosity phenotype K. pneumoniae

Methods

We conducted a retrospective study at University of the Ryukyus Hospital between January 2021 and November 2022, extracting patients with HMV-Kp bacteremia. K. pneumoniae isolates were subjected to String test (Fig 2), antimicrobial susceptibility testing, and genomic analysis. Whole-genome sequencing and genomic analysis were conducted to identify multilocus sequence type (MLST), K capsule serotype, virulence genes, and antimicrobial resistance genes.Figure 2.String test

Results

During the study period, 29 cases of K. pneumoniae bacteremia were identified, with six cases of HMV-Kp bacteremia. Five of these cases were male patients and had organ abscess formation (Table 1). The results of the genomic analysis are shown in Table 2. All six HMV-Kp strains were positive for rmpA/rmpA2. MLST and K serotyping revealed that two isolates belong to ST23-K1 and ST86-K2, a known hypervirulent clone. All strains contained virulence genes, with the two ST23-K1 strains carrying all the typical hvKp virulence genes. No strains harbored ESBL or carbapenemase genes.Table 1.Clinical backgrounds of the cases.Table 2.Sequence typing and Virulence genes of the isolates.

Conclusion

All HMV-Kp strains isolated in this study carried virulent genes, including the hvKP clones ST23-K1 and ST86-K2. The String test for HMV phenotype confirmation appears useful to estimate the presence of hvKp. Our findings provide insights into the virulence and potential clinical implications of HMV-Kp isolates in Japan, highlighting the need for further investigation and monitoring.

Disclosures

Kazuko Yamamoto, MD, PhD, Fisher & Paykel Healthcare: Grant/Research Support|Kirin Holdings Co.: Grant/Research Support
311. Heterologous immunity and host susceptibility to emerging alphaviral infections
Authors: Vittor Amy Y , Pu Ruiyu , Paul Carrera Jean , Long Maureen T , Lopez Sandra , Weaver Scott , Morris John G , Pascual David
Published: November 2023

Background

In 2010, Madariaga virus (MADV) newly emerged in Darien, Panama, where Venezuelan equine encephalitis virus (VEEV) is endemic. We noted an inverse relationship between VEEV and MADV seroprevalence in humans, prompting the study of heterologous immunity in alphaviral infection.

Methods

Using patient samples from Panama, we examined antibody-dependent cell mediated cytotoxicity (ADCC) and antibody-dependent cell mediated lysis assays (ADCL) to three viruses: Mayaro virus (MAYV), Madariaga virus (MADV), and the vaccine strain of Venezuelan equine encephalitis virus (TC83). We developed an ADCC assay using adherent target cells (human dermal fibroblasts), and high-throughput immunofluorescence microscopy. We determined ADCL activity using alphavirus-infected K562 cells and flow cytometry. We further defined the specificity of antibodies by plaque reduction neutralization tests, whole viral antigen and virus-specific recombinant glycoprotein (rGP) ELISAs.

Results

Sera from alphavirus-exposed individuals demonstrated significantly greater ADCC and ADCL activity compared to alphavirus-naïve sera. Blocking CD16 abrogated this effect, confirming the role of natural killer cells in inducing ADCC and ADCL. The relationship is asymmetric; prior VEEV exposure yields a high degree of homologous and heterologous ADCC and ADCL activity, whereas MADV and MAYV exposure results in heterologous ADCC and ADCL activity no different than alphavirus-negative controls. We observed a strong association between ADCC/ADCL activity and whole viral antigen ELISA titers, but not rGP ELISA nor neutralization titers, suggests that the viral antigens that elicit ADCC and ADCL may be nonstructural proteins.

Conclusion

Here we demonstrate that VEEV antibodies are active against heterologous alphaviral infections in vitro by ADCC and ADCL, but not by neutralization. This has implications for vaccine development. Eliciting an antibody response that is not only neutralizing, but also generates antibodies with ADCC and ADCL activity may produce broader protection against viral variants or antigenically similar viruses. Additionally, these results provide insight into immunological mechanisms underlying the emergence potential of a novel virus.

Disclosures

All Authors: No reported disclosures
312. Strain Engraftment and Gene Transfer in a Fecal Microbiota Transplantation Cohort
Authors: Brink Catherine , Conrad Roth , Babiker Ahmed , Hatt Janet , Barrios-Steed Danielle , Kraft Colleen S , Woodworth Michael H , Konstantinidis Konstantinos
Published: November 2023

Background

Fecal microbiota transplantation (FMT) is a procedure that has gained popularity due to the high efficacy in treating recurrent Clostridioides difficile infections (RCDI) and other conditions associated with a dysbiotic gut microbiome. Despite the widespread acceptance of the technique, repeating its success in RCDI treatment in other diseases has been difficult due to the individual-level variation in disease effects on the gut and the emphasis on taxonomic, rather than functional, microbiome analyses. We present a metagenomic analysis of the use of FMT to treat renal transplant patients infected with multidrug-resistant organisms (MDROs).

Methods

DNA was extracted from longitudinally collected participant stool samples before and after FMT. Reads were assembled and binned into metagenome assembled genomes (MAGs), which were then mapped back to the reads to calculate relative abundance, breadth and sequencing depth in each patient sample. This allowed us to assess the species-level changes in the composition of patient microbiomes after FMT treatment.

Results

We identified four MAGs, representing close relatives of Akkermansia muciniphila, Dakarella massiliensis, Mesosutterella multiformis and Waltera intestinalis, that showed a pattern of engraftment (absent or undetectable before FMT, but present for at least two consecutive timepoints after treatment) in FMT-treated patients. We also observed clear evidence of a donor MAG closely related to Faecalibacterium gallinarum replacing patient MAGs identified as Faecalibacterium hattori, revealing a potential mechanism of successful FMT treatment though a resistant strain in the patient microbiome likely being outcompeted by a drug-susceptible strain of the same species from the donor.

Conclusion

Herein we elucidated the taxonomic changes that take place in renal transplant patient gut microbiomes with reduced MDRO colonisation in response to FMT treatment. Future efforts will aim to identify the shifts in the functional gene profiles of the patient microbiomes to allow for a deeper understanding of the mechanisms underlying successful FMT treatments and further the rational design of live biotherapeutic consortia to treat antibiotic-resistant colonisation.

Disclosures

Ahmed Babiker, MBBS, Roche: Advisor/Consultant
316. Leveraging the Electronic Health Record to Improve OPAT Discharges at University of Colorado Hospital
Authors: Allen Lorna , Montague Brian T , Koehler Sandra , Hallman Heather , Olsen Nicholas L , Pisney Larissa
Published: November 2023

Background

Outpatient parenteral antimicrobial therapy (OPAT) discharges at University of Colorado Hospital (UCH) are not standardized and require a highly coordinated, multidisciplinary approach. Discrepancies and omissions on the discharge medication list have led to near miss and patient harm events during transitions of care including missed doses, wrong doses, and inappropriate cessation of IV antimicrobials. The purpose of this project was to improve patient safety and provider efficiency through streamlining and standardizing the OPAT discharge process.

Methods

In September 2022 we implemented a two pronged intervention on the UCH Anschutz campus. A change in the workflow designated the Infectious Disease provider to place the antimicrobial on the discharge medication list. In addition, an OPAT navigator tool was developed in collaboration with an EPIC build team and launched in the electronic health record (EHR). The navigator utilizes discrete data entry into flow sheet rows to populate a standardized OPAT order that is automatically pulled onto the after visit summary.

Results

Baseline data collected from 10/2020 - 8/2022 showed that 48% (n = 131) of OPAT patients had either incorrect or omitted orders on the discharge medication list. Post intervention data collected from 10/2022 - 3/2023 showed a mean of 98% (n= 433) of OPAT patients had the correct IV antimicrobial on the discharge medication list. Four steps were eliminated from the previous discharge workflow.

Conclusion

Transitions in care are a vulnerable period for high risk OPAT patients. This project has been successful in achieving the primary aims of improved accuracy of IV antimicrobials on the discharge medication list. Continued efforts will be focused on sustainability as well as the potential for expansion to additional UCHealth sites.

Disclosures

Lorna Allen, FNP-C, MERCK: Grant/Research Support Brian T. Montague, DO MS MPH, Eli Lilly: Grant/Research Support|Regeneron: Grant/Research Support
332. Factors Associated with Readmission in Patients with End-Stage Renal Disease on Hemodialysis Discharged on Outpatient Parenteral Antimicrobial Therapy
Authors: Ismail Ghaleb , MacDonald Nancy , Kenney Rachel M , MULUGETA Surafel , Gendjar Suzette , Daifi Chantale
Published: November 2023

Background

Outpatient parenteral antimicrobial therapy (OPAT) is a popular option for patients who require extended treatment with antimicrobials. OPAT in patients with end stage renal disease (ESRD) on hemodialysis (HD) has unique considerations and regimens that facilitate vein preservation as a priority. This study aimed to characterize patients with ESRD on HD discharged on OPAT and identify factors associated with poor outcomes.

Methods

This was an IRB–approved retrospective cohort of patients ≥ 18 years with ESRD on HD who were discharged between 1/1/20 and 8/30/22 with at least one week of OPAT. Enrolled patients were divided into two equal groups depending on their 60-day readmission status. Patients were excluded if they were admitted on OPAT prior to admission or expired within 30 days of the initial OPAT discharge, incarcerated, or if the discharge was self-directed. To identify risk factors for readmission, patients who had an unplanned all-cause 30-day readmission were compared with those not readmitted. Other safety measures collected include transitions of care process measures, pharmacist collaboration with patient education and follow-up monitoring.

Results

162 patients (67 females, 95 males; median age 59 years) were included. The most common reason for OPAT was bloodstream infection (51%). Vancomycin was the most prescribed (50%). Nine patients in the readmitted group reported adverse events compared to 31 in the readmitted group (p = < 0.001). Patients in the non-readmitted were statistically more likely to have a pharmacist infection treatment plan note prior to discharge (p = 0.036) and statistically more likely to attend infectious disease (ID) follow-up appointments (p = 0.001). A multivariable regression identified that being female, having diabetes mellitus, or congestive heart failure are associated with increased risk of unfavorable outcomes (Adjusted odd ratio = 3.352, 1.75, and 1.671 respectively).

Conclusion

This study suggests that OPAT optimization and patient education by a pharmacist, and attending follow-up ID appointments reduced the risk of readmission for patients with ESRD on HD.

Disclosures

All Authors: No reported disclosures
352. Post-Discharge Microbiology Review by Infectious Diseases Pharmacists is Impactful
Authors: Van Abel Amy , Pertzborn Margaret , Lane Trudi , Schreier Diana , Teaford Hiliary R , Virk Abinash , Willis Courtney , Rivera (O'Connor) Christina G
Published: November 2023

Background

Post-discharge culture and susceptibility review has been described in emergency department and urgent care settings, but there is a lack of published literature describing culture review after acute care hospitalizations. Awaiting microbiology results can impede timely patient discharge. However, discharging patients while microbiology results are pending may result in suboptimal therapy or lost opportunity for additional testing/follow up. We implemented an antimicrobial stewardship effort to identify microbiology tests that result post-discharge utilizing a custom report in the electronic medical record (EMR).

Methods. This retrospective descriptive study included adult patients ( >18 years of age) at 4 sites within Mayo Clinic from 1/1/2019 to 2/28/2023. Eligible patients had a hospitalization with an ID consult and an abnormal culture that was reviewed by an antimicrobial stewardship pharmacist after discharge. Urine cultures were excluded. The details of pharmacist-initiated antimicrobial stewardship interventions based on the culture review were identified by an EMR based research report.

Results

A total of 6803 patient encounters with at least 1 microbiology result reviewed post-discharge were identified. Patients were 40% female with a median age of 62 years. Patient race was 89.8% white, 4% black/African American, 1.5% Asian, and < 1% other. Of these patients, 1983 (29%) had at least one pharmacist intervention. A total of 169 (2.5%) of these patients had multiple interventions. Interventions included modification of antimicrobial therapy, addition of susceptibility testing, or additional follow up (labs, imaging, or patient visits). Median time from culture update to pharmacist review was 27.2 hours. Median length of hospital stay was 5 days and discharge disposition was home with self care (65%), home with home health or hospice (22.7%), or discharge to another acute care or skilled nursing facility (12.3%).

Conclusion

Outpatient review of post-discharge culture updates utilizing EMR reporting led to substantial interventions impacting antimicrobial treatments.

Disclosures

Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria
389. PediCoViral: Clinical Outcomes of COVID-related Co-viral infections in Children
Authors: Anosike Brenda I , Sharma Shiv M , Sarill Kiera , Alrikaby Jassour , Duong Tim Q , Herold Betsy
Published: November 2023

Background

During the earlier phase of the COVID-19 pandemic, published reports demonstrated low rates of COVID co-viral infections. Upon relaxing public health measures, the epidemiology of known respiratory viral pathogens had dramatically shifted as the pandemic evolved. Little is known about the clinical impact of co-viral infections in children post-Omicron wave. This study investigates the clinical outcomes among children, adolescents, and young adults who test positive for SARS-CoV-2 [COVID] alone compared to those with COVID co-viral infection with either RSV or Influenza [Flu] A/B [denoted as COVID+]

Methods

We conducted a retrospective study of subjects ≤ 21 years of age who tested positive for SAR-CoV-2 presenting to the Children’s Hospital at Montefiore, Bronx, NY from 12/1/2021 to 1/15/2023. Laboratory confirmation was established using a multi-target PCR assay for influenza A/B, RSV, and SARS-CoV-2. The primary outcomes were hospitalization, need for invasive mechanical ventilation (IMV), and mortality. Demographic and patient outcomes were extracted using ATLAS database.

Results

Among 8307 subjects who tested positive for COVID alone, 8.5% (708) were hospitalized with a mean age of 8.7 years (SD=7.8) while mean age of those with COVID+ was 5.0 years (SD=4.4). Hospitalization rates for COVID alone, COVID+Flu, and COVID+RSV were 6.4%, 32.2%, and 57.7%, respectively (p< 0.001). COVID positive children ≤ 5 years of age with or without a second virus were more likely to be hospitalized than other age group (p< 0.001). When comparing COVID+Flu vs. Flu alone (32.2% vs. 4.3%, p< 0.001) or COVID+RSV vs. RSV alone (57.7% vs. 15.8%, p< 0.001), hospitalization rates were higher for those with COVID co-viral infections. No increase in mortality was observed.Figure 1.Patient Flow ChartTable 1.Patient Demographics and Characteristics*unadjustedTable 2.Clinical outcomes of pediatric patients

Conclusion

This single center retrospective study demonstrates that SARS-CoV-2 coinfection with RSV or Influenza is associated with increased risk for hospitalization compared to SARS-CoV-2, RSV or influenza alone. Hospitalization rates were higher in younger children. Further studies are needed to identify the mechanisms driving the increased morbidity associated with these coinfections.

Disclosures

All Authors: No reported disclosures