bluuebunny/crossref_metadata_2025 huggingface dataset:
2956. Increased Microbiota Alpha Diversity is Associated with Decreased Hospital Mortality in Medical Intensive Care Unit Patients
Authors: Sansom Sarah E , Bassis Christine , Schoeny Michael , Thotapalli Lahari , Fukuda Christine , Dangana Thelma E , Bongu Jahnavi , Jaskowiak Anne , Bekele Selamawit , David Michael Z , Dubberke Erik R , Young Vincent B , Hayden Mary K
Published: November 2023

Background

Characteristics of the gut microbiome may be useful to predict resistance to colonization and expansion of pathogenic organisms such as C. difficile. In this study, we evaluated whether inclusion of microbiome characteristics improved a clinical prediction model for in-hospital mortality.

Methods

Rectal or fecal swab samples were collected daily from medical intensive care unit (ICU) patients from three hospitals between 2017-2019 and underwent 16S rRNA gene sequencing of the V4 region. Patient admissions with ≥1 rectal swab collected < 48hrs from ICU admission were randomly selected 2:1 for calibration and validation analyses. Independent variables included Shannon Index, Microbiome Health Index, Community Type (CT) and relative abundance (RA) of specific bacterial taxa based on 3% sequence difference or class-level classification. The RA of each bacterial taxon was range-standardized (95%) and scaled to analyze a 10% relative difference within each taxon’s range. Logistic regression models identified microbiome characteristics at admission that were associated with in-hospital mortality. Fixed effects were included in all models to account for microbiome differences between facilities.

Results

There were 1365 patient admissions (910 calibration, 455 validation) analyzed (Table), of which 134 (96 calibration, 38 validation) died during hospitalization. Increase in Shannon Index by 1 [OR 0.66 (0.51-0.84), p=0.001], 10% relative increase in the RA of Bacilli [OR 1.15 (1.08-1.22), p< 0.001] and 10% relative increase in the RA of Enterococcus [OR 1.10 (1.04-1.14), p=0.001] were associated with in-hospital mortality in calibration models after controlling for Charlson Comorbidity Index [OR 1.23 (1.15-1.32), p< 0.001]. Increase in Shannon Index by 1 [OR 0.88 (0.57-1.38), p=0.581] had the same direction and similar odds in the validation cohort (Figure), supporting the findings of the calibration model.

Conclusion

In this secondary analysis of a large, multicenter, prospective medical ICU cohort, we found that higher alpha diversity of the gut microbiome was associated with decreased odds of in-hospital mortality.

Disclosures

Michael Z. David, MD PhD, Covance: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support Erik R. Dubberke, MD, MSPH, Abbott: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Grant/Research Support|Merck and Co.: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Seres Therapeutics: Advisor/Consultant|Summit: Advisor/Consultant|Theriva Biologics: Grant/Research Support Vincent B. Young, MD/PhD, ASM: Senior Editor|Debiopharm: Advisor/Consultant|Vedanta Biosciences: Advisor/Consultant
2331. Characteristics Associated with Hospital-Acquired COVID-19 Infections in Los Angeles County
Authors: Sato Heidi D , OYong Kelsey , Rubin Zachary
Published: November 2023

Background

Few studies have characterized nosocomial transmission of SARS-CoV-2. We examined factors associated with hospital-acquired infections (HAIs) rates for SARS-CoV-2 in Los Angeles County (LAC).

Methods

In this retrospective cohort study, data were collected from 70 acute care hospitals between July 1, 2020 and March 31, 2022. We defined COVID HAIs as a patient with laboratory-confirmed SARS-CoV-2 (PCR or antigen test), which was first positive 4 or more days after hospital admission and before discharge. Community transmission (CT) level was calculated by dividing new cases within the past 7 days by the population in the county (per 100,000). Variant predominant periods were defined as periods when the variant exceeded 50% of sequenced specimens during the specimen collection month. The percent of core healthcare personnel (HCP) receiving a completed COVID vaccination series (as of 11/28/2021) was obtained from the National Healthcare Safety Network (NHSN). Incidence rates were calculated using patient-days as a denominator, as reported to NHSN. Mantel-Haenszel test was performed to assess COVID HAIs and predominant variant periods, controlling for effect of CT level. We analyzed hospital characteristics associated with incidence rate using multiple regression (SAS 9.4).

Results

During the 21-month study period, 2107 patients were identified as having COVID HAIs at 70 hospitals using the standardized definition. COVID HAIs were more likely to occur during high CT levels (RR=6.2; 95% CI=4.9, 8.0) and when the Omicron variant was predominant (RRCMH = 1.2; 95% CI=1.1, 1.4). In multivariate analysis, a higher rate of COVID HAIs was associated with hospitals unaffiliated with medical schools (β= -30.9, p< .05), lower HCP vaccination coverage (β= -0.6, p< .05), more hospital beds (β= 0.1, p< .05), and ownership type (β= 19.2, p< .01). In comparison to government hospitals, HAIs were three times more likely to occur in for-profit hospitals (95% CI=2.6, 3.6) and 1.4 times more likely to occur in not-for-profit hospitals (95% CI=1.2, 1.7).

Conclusion

COVID HAIs are more likely to occur during high transmission periods and at hospitals without medical schools, with for-profit ownership, lower HCP vaccination rates, and with a higher number of beds.

Disclosures

All Authors: No reported disclosures
127. Evaluation of Real-Time Verigene Blood Culture Alerts on Time to Optimal Antibiotic Therapy
Authors: Adams David T , Kaur Satwinder S
Published: November 2023

Background

Verigene blood culture (VBC) results can help facilitate reductions in time to optimal antimicrobial therapy (TTOT), potentially leading to improved clinical outcomes. We sought to evaluate if TTOT could be further reduced by implementing automated real-time VBC alerts delivered to the antimicrobial stewardship (AMS) team.

Methods

A retrospective observational cohort study of adult patients with bacteremia and a VBC result from May to September 2021 comparing outcomes when alerts resulted while AMS team members were working compared to not working. AMS team members review all positive blood culture alerts and make recommendations to the treating physicians based on results and current antimicrobial regimens. Excluding patients with a VBC result of Staphylococcus species, Streptococcus species, S. epidermidis, or no target detected, patients with an opportunity for change in their empiric antimicrobial regimen based on the VBC result were included.

Results

In total, 207 patients met inclusion. The most frequent organisms encountered with an opportunity for intervention were E. coli (n=92) and S. aureus (n=49). The most common source was urinary (37.2%). Mean TTOT was shorter in the VBC+AMS group (41.4 hours) compared to the VBC only group (53.1 hours) regardless of whether the AMS team recommendation was accepted, P = .035. This difference was unsurprisingly larger when evaluating only those in the VBC+AMS group where the recommendation was accepted (18.9 hours) compared to all other patients (54.6 hours), P = < .0001. All-cause in-hospital mortality was significantly lower in the VBC+AMS group (12.3%) compared to the VBC only group (26.9%), P = .02. Similar rates of change to optimal therapy at any point during the admission (91%) were observed in the VBC only and VBC+AMS groups.

Conclusion

The implementation of a real-time alert system to communicate VBC results to the AMS team resulted in a significant reduction in TTOT and in-hospital mortality when alerts occurred while AMS team members were working. Given the high antibiotic optimization rates in both groups but a difference in mortality, further studies are needed to identify if there is an association between TTOT and improved clinical outcomes beyond the benefits of timely effective antimicrobial therapy.

Disclosures

All Authors: No reported disclosures
2389. Surveillance evaluation of COVID-19 pharmacovigilance—Karakalpakstan, Uzbekistan, 2022
Authors: Tursinov Yunis , Kurbanov Botirjon , Denebayeva Alfiya , Horth Roberta , Nabirova Dilyara
Published: November 2023

Background

COVID-19 vaccines are safe and effective. Rapid rollout of vaccines reduced COVID-19 morbidity and mortality globally. Pharmacovigilance systems have ensured safety of these vaccines. Well-functioning vaccine safety surveillance builds public confidence in vaccine programs, but these systems may be lacking in limited-resource settings. To identify gaps in pharmacovigilance surveillance, we conducted an evaluation in Khojaly District, Uzbekistan, with population of 120 thousand people.

Methods

We reviewed regulatory documents related to COVID-19 vaccination and registration of side effects after immunization. We also conducted a survey in April 2022 of 30 healthcare providers in 5 of 10 polyclinics in Khojaly districts whose responsibilities included vaccination of the population. The survey asked about their knowledge and practices related to adverse events following immunization (AEFI). AEFI was defined as any health condition that occurs after immunization and does not necessarily have a causal relationship with vaccination.

Results

From April 2021 to March 2022, 78,453 doses of COVID-19 vaccines were given in Khojaly district. Of these, 70% of doses were from ZF-UZ-VAC-2001 (Zifivax) vaccine doses, an adjuvanted protein produced in Uzbekistan (Table 1), 9% Pfizer–BioNTech vaccine doses and 7% Moderna vaccine doses. All AEFIs are mandatorily reported by providers (Figure 1). Of 2,464 reported AEFI, majority (75%) were procedural errors, 1% were mild allergic reactions, and only 2 cases of anaphylactic shock. Among healthcare providers surveyed (Table 2), 33% did not know where to report the AEFI and 10% reported large patient load as a barrier to reporting. Half (50%) of providers had encountered a case of AEFI following COVID-19 vaccination, 10% encountered a severe AEFI, and 43% submitted an AEFI report. In record review, we identified cases of AEFI that had only been registered in patient medical charts, and not reported into the AEFI surveillance system.

Diagram of AEFI surveillance for COVID-19 vaccines in Uzbekistan

COVID-19 vaccine doses and reported AEFI, Khojaly district, Uzbekistan, 2021-22

Knowledge of AEFI and AEFI reporting among COVID-19 vaccine providers, Khojaly district, Uzbekistan, 2021-22

Conclusion

Important considerations were identified in COVID-19 pharmacovigilance surveillance. The system can be strengthened through increased training of healthcare providers in standard operating procedures for identifying, reporting and investigation AEFI cases associated with COVID-19 vaccines.

Disclosures

All Authors: No reported disclosures
2397. Infective Endocarditis is Associated With Higher Mortality and Worse Clinical Outcomes in Patients Hospitalized with a Concomitant Diagnosis of Heart Failure
Authors: Sharath Deepali Boothankad , Khokhlov Leonid , Fatuyi Michael , Patel Anar
Published: November 2023

Background

The United States has the highest incidence of infective endocarditis (IE) in the world at 15 per 100,000 people with increasing incidence due to the aging population and growing rates of intravenous drug use (IVDU). Heart failure (HF) is the most common complication and the main cause of death in patients with IE. There is limited evidence on the clinical outcomes in IE populations affected by HF. We sought to investigate the demographics and outcomes of this cohort of patients.

Methods

The Nationwide Inpatient Sample (NIS) database was queried between 2017-2020 for adult patients who were hospitalized with the primary diagnosis of IE. The secondary diagnosis was HF. The primary outcome evaluated was inpatient mortality. The secondary outcomes were severe sepsis, septic shock, cardiogenic shock, cardiac arrest, invasive mechanical ventilation, length of stay (LOS), and total hospital charge. Multivariable logistic and Poisson regression analyses were used to estimate clinical outcomes. P-value < 0.05 was significant.

Results

We identified a total of 250,070 hospitalizations with the diagnosis of IE in 2017-2020, 95,320 of which also had HF (38%), 45% of which with specified systolic heart failure. Patient characteristics are shown in Table 1. Patients admitted with IE and concurrent HF had significantly higher inpatient mortality and worse clinical outcomes. (Table 2 and Figure 1).

Figure 1

Clinical Outcomes in Patients with IE and Concomitant HF

Conclusion

Our study showed that patients with IE and concurrent HF tended to be older males, Caucasians, and obese. This cohort was more likely to have atrial fibrillation, diabetes mellitus, dyslipidemia, acute coronary syndrome, ST elevation MI, acute renal failure, and chronic kidney disease (Table 1). Hence, cardiac dysfunction in IE patients is associated with renal and pulmonary impairment, higher rates of infectious complications, and a more severe hospitalization course. This can be explained by the myocardial dysfunction that predisposes to end-organ damage. When managing patients with IE and co-existing HF, clinicians should be aware of this predictor of negative outcomes. Further studies are necessary to describe the more recent trends given better antibiotic therapy, control of IV drug use, and earlier surgical interventions.

Disclosures

All Authors: No reported disclosures
2398. Short and Long-Term Outcomes of Patients Admitted with Infective Endocarditis Who Undergo Patient-Directed Discharge
Authors: Crooker Kyle , He YuTing , Hickey Tess , HoddWells Max , Sarathy Ashwini , Teng Torrance , Muniz Sean , Lor Jennifer , Chang Amy , Tompkins Bradley , HALE A N D R E W
Published: November 2023

Background

Infective endocarditis (IE) results in high morbidity and mortality. Guidelines for IE recommend prolonged intravenous antibiotics that can result in extended hospitalization, but some patients experience patient-directed discharges (PDD) prior to completion. There is a current lack of literature clearly defining long-term outcomes and optimal treatment strategies in patients with IE who experience PDD.

Methods

This is a retrospective cohort study comparing outcomes of adult patients with infective endocarditis at a single center from 2010 to 2020 who experienced patient-directed discharge versus those who did not. The primary outcomes were 30 day, 90 day, and 2 year re-admission and mortality rates related to IE. The secondary outcome was worsened IE, which encompassed pertinent clinical and microbiologic outcomes.

Results

391 patients were identified and included. Of these 47 (12%) experienced PDD and 344 (88%) did not. The PDD cohort was younger (mean age 33.3y (IQR 27.7 to 37.6) vs 60.1y (IQR 37.4 to 72.5 (p< 0.01)); more likely to be on Medicaid (75% vs 29% (p< 0.01)), undomiciled (17% vs 6.4% (p=0.01)), using intravenous drugs (87% vs 27% (p< 0.01)), and have psychiatric comorbidities (53% vs 33% (p< 0.01)). The PDD cohort received a mean of 17.3 days of IV antibiotics vs 36.5 days in the controls (p< 0.01) with 26 (55%) of the PDD cohort getting oral antibiotics upon discharge with an average duration of oral antibiotics of 29.3 days. Compliance on oral antibiotics was low in the PDD cohort (46%). There was no significant difference in death related to IE (0% vs 4% (p=0.3)). 30 and 90 day readmission rates were significantly higher in the PDD cohort (38% and 47% vs 11% and 15% (p< 0.01)). The PDD cohort was significantly more likely to be readmitted with new heart valves involved (21% vs 3% (p< 0.01)), new paravalvular abscess (9% vs 1% (p< 0.01)), different causative organisms (40% vs 18% (p< 0.01)), and/or new metastatic sites of infection.

Conclusion

Adult patients with IE who experience PDD are more likely to be younger, undomiciled, to use intravenous drugs and to have a psychiatric comorbidity. These patients have significantly worse outcomes from IE. Further treatment and outreach strategies in this patient population are essential to improve outcomes.

Disclosures

All Authors: No reported disclosures
2424. Outcomes of vascular graft infections without graft removal treated via OPAT: A retrospective cohort study
Authors: Hennigan Oisin , Geoghegan Laoise , Reynolds Maura , Morrison Elaine , Clarke Susan
Published: November 2023

Background

Vascular graft infections (VGI) are a rare complication of endovascular aneurysm repair (EVAR) with significant associated morbidity and mortality. While surgical removal of infected material may be the preferred treatment, for patients who have inoperable VGIs conservative management with antibiotics may be the only option.

This study aims to investigate the outcomes including mortality, re-admissions, relapse within 12 months, microbiological data, bed days saved, and use of long term suppressive antibiotics in patients with VGI where the graft is retained.

Methods

This single centre retrospective study evaluated all patients with a VGI between 2013-2021 who were treated via OPAT. Patient information was gathered from the local OPAT database and via the patients’ electronic patient records.

Results

23/27 OPAT episodes were managed without graft removal. 52% were male. The median age was 70yrs (range 45-81). Median IV treatment of 6 weeks.

All patients received anti Staphylococcal cover while 14/23 episodes includes anti-MRSA agents.

6/23 episodes required re-admission over the course of OPAT treatment, of which 2 were OPAT related (1 DVT, 1 ADR) while 4 were disease related. 4/23 patients died within the first year of treatment all of which were secondary to their infected graft. In the remaining 19 patients there were no relapses by the 12 month follow up period.

13/16 patients who successfully completed their OPAT course were commenced on long term oral suppression.

32 bed days were saved per OPAT episode, a 77.0% reduction in overall hospital stay.

Type of infection

Pie chart breaking down the types of Vascular Graft Infections affecting the 23 patients included in this case series.

PO Suppressive Abx

Pie chart displaying the PO suppressive antibiotics chosen for the 19 patients who completed OPAT successfully.

Culture results

Bar chart displaying culture results. Sub categories include Gram-positive, Gram-negative, Fungal, Nil positive culture results and number of patients with polymicrobial culture results

Conclusion

Limited data shows mortality associated with VGIs ranges from 25-55%. This study demonstrates successful outcomes in our cohort of patients treated conservatively without surgery but focussed antibiotic therapy long term. It was well tolerated in the OPAT setting after initial stabilisation in hospital and OPAT can be considered a safe option for VGI infections. The small study shows a 1-year survival rate of 82% comparing very favourably with other published data.

Disclosures

All Authors: No reported disclosures
2463. Bacterial Infections in Intensive Care Unit patients in a large general hospital, Kazakhstan, 2022
Authors: Yergaliyeva Ademi , Gazezova Saya , Ayapova Gulzhan , Ibragimova Elvira , Nabirova Dilyara , Horth Roberta
Published: November 2023

Background

Between January and April 2022, an audit of surveillance data revealed five cases of bloodstream Acinetobacter baumannii infection in intensive care unit (ICU) patients in a large general hospital. Bacterial infections such as Acinetobacter baumannii contribute to significant mortality and complications of treatment in ICU patients. We aimed to describe bacterial pathogens and their resistance profile among ICU patients to inform infection prevention and control programs.

Methods

We conducted a cross-sectional study of patients admitted to the ICU of a large general hospital in Kazakhstan from January to April 2022. The study included all patients ≥ 18 years old diagnosed with a bacterial infection as detected in blood, urine or sputum samples. Demographic, clinical, and laboratory data were abstracted from medical records.

Results

Among 65 patients identified, 54% were male, mean age 64 years (range 20-93). Majority (35%) were admitted directly to the ICU, 15% had been transferred to the ICU from the infectious surgery department, 14% from the stroke department, and 5% from the gynecology department. Sixty-eight percent (44/65) of patients had surgery prior to transfer to the ICU. The most frequent pathogen in the study patients was Acinetobacter baumannii 63% (n=41). Of which, 15% was detected in blood, 41% in urine, and 44% in sputum. The hospital only tests for drug-resistance for the prescribed antibiotic, and 63% (26/41) of strains tested were resistant to their prescribed medicines. Klebsiella pneumoniae was detected in 22% (n=15) patients. Of which, 60% was detected in sputum, 20% in urine and 20% in blood. Also, 60% were drug-resistant. Staphylococcus aureus was detected in 11% of patients. Of which, 57% was drug-resistant in sputum. Overall 60% (39/64) of pathogens tested had resistance for the antibiotic prescribed, but there was no evidence that prescribed antibiotics changed based on resistance results.

Antimicrobial resitance and antibiotics prescribed to patients in an ICU of a large general hospital (n=65), Kazakhstan, 2022

Map of bacterial infection in ICU patients admitted from different wards in a large general hospital, Kazakhstan, 2022

Conclusion

The identification of infectious pathogens with demonstrated drug resistance reinforces the need for improved basic infection control practices and the need for improved antimicrobial stewardship. Increased surveillance and reporting of hospital-acquired infections is needed.

Disclosures

All Authors: No reported disclosures
2469. Comparative Genomics Uncovers Strain Diversity and Possible Unrecognized Transmission of MDROs among Hospitalized Patients
Authors: Koundakjian Dylan , Strudwick Amanda F , Page Alex , Van Riel Julia , Gooden D’Ante , Satola Sarah W , Bombin Andrei , Read Timothy D , Jacob Jesse T , Babiker Ahmed , Woodworth Michael H
Published: November 2023

Background

Contamination of the healthcare environment by colonized patients is an important source of multidrug-resistant organism (MDRO) transmission. We aimed to determine MDRO room contamination of patients with MDRO clinical cultures to test diversity of dominant strains in colonizing isolates and detect possible transmission.

Methods

Inpatient cases with clinical cultures positive for CRE, extended-spectrum cephalosporin resistant Enterobacterales (ESCRE), CR-Pseudomonas and VRE were eligible for inclusion. Patients on the same unit without positive MDRO clinical cultures in the prior 90 days were selected as controls. Participant inguinal and perirectal sites were sampled by E-swab. Three patient room surface composites were sampled with sponge sticks on the same day. Colonies on differential and selective media were identified by MALDI-TOF with Vitek2 antimicrobial susceptibility testing. Isolates underwent genome sequencing. Clustered gene alignment and average nucleotide identity were compared for conspecific isolates. Transmission was defined as isolation of conspecific MDRO strains with > 99.9% ANI in two or more patients.

Results

Twelve cases and 5 controls were included. Among cases, the same clinical MDRO was detected in 91% (10/11, one patient declined sample collection) of patient-site cultures and in 42% (5/12) of environmental cultures. Among controls, an MDRO was detected in 60% (3/5) of patient samples but no MDROs were found in environmental samples. Antibiotic susceptibility was similar between conspecific patient clinical, colonizing, and environmental isolates. Among isolates sequenced, SNP analysis confirmed genetic relatedness between colonizing and invasive strains and revealed unrecognized unit-based MDRO transmission.

Cases and Controls had similar clinical features

Whole genome sequencing demonstrated patient colonization with multiple conspecific strains and uncovered potential unit-based transmission of colonizing isolates

Conclusion

There is significant environmental contamination from hospitalized patients with clinical MDRO culture positivity. Whole genome sequencing demonstrated patient colonization with multiple conspecific strains and uncovered potential unit-based transmission of colonizing isolates, which may be potentiated by environmental contamination. Further research is needed to understand if reducing patient MDRO colonization could reduce environmental contamination and transmission.

Disclosures

Ahmed Babiker, MBBS, Roche: Advisor/Consultant
2473. Rates of Antibiotic Resistant Infections in Hospitalized Patients with Hematologic and Non-Hematologic Cancers, 2019
Authors: McCarthy Natalie , Lutgring Joseph D , Baggs James , Wolford Hannah , Reddy Sujan
Published: November 2023

Background

Patients with cancer have risk factors for developing both hospital-onset (HO) and antibiotic resistant (AR) infections such as high antibiotic use, long lengths of stay, and device utilization. Understanding the epidemiology of AR infections in this population can inform clinical management and prevention strategies. We aimed to describe the rates and proportions of AR infections in hospitalized patients with cancer.

Methods

Using the PINC AI Healthcare Database, we included adult discharges from 2019 among facilities reporting microbiology data. We identified patients with at least one cancer diagnosis from the Healthcare Cost and Utilization Project’s Clinical Classifications Software Refined categories and Elixhauser Comorbidity Software Refined for ICD-10-CM. We calculated age-standardized rates of AR infections among cancer patients per 10,000 discharges, stratified by community-onset (CO: ≤ day 3 of hospitalization) and HO (≥ day 4 of hospitalization), and hematologic and non-hematologic cancer types. Hematologic cancers included lymphoma, leukemia, myeloma and myelodysplastic syndrome. We also examined the proportion of AR infections in patients with cancer among all AR infections in the cohort.

Results

Of >2 million discharges from 277 facilities, 11.4% were patients with cancer. Compared to all patients, cancer patients had higher rates of infection with CO and HO vancomycin resistant Enterococcus (VRE) and carbapenem resistant Enterobacterales (CRE), and HO Enterobacterales with AR phenotypes suggestive of extended-spectrum β-lactamase (ESBL) production (Table 1). Compared to patients with non-hematologic cancer, patients with hematologic cancer had higher rates of all AR infections, except for CO carbapenem resistant Acinetobacter spp. (CRAsp) infections (Table 1). For most AR infections, cancer patients made up a greater proportion of all HO AR infections compared to CO AR infections (Table 2).

Conclusion

Patients with cancer had higher rates of several AR infections compared to all patients. To decrease the burden of AR infections in this population, infection prevention strategies may focus on VRE, ESBL, and CRE pathogens, as well as HO infections, in all cancer patients, particularly those with hematologic cancer.

Disclosures

All Authors: No reported disclosures
2479. Impact of the COVID-19 pandemic on the hospital acquisition of multidrug-resistant organism in two Greek hospitals
Authors: Karakosta Polyxeni , Kousouli Elisavet , Vourli Sophia , Georgiou Panagiota Christina , Mamali Vasiliki , Zarkotou Olympia , Pournaras Spyros
Published: November 2023

Background

COVID-19 pandemic pushed back progress for combating antimicrobial resistance (AR). We aimed to provide a proxy measure for MDRO Hospital Acquisition in two Hospitals following COVID-19 pandemic.

Methods

Active surveillance for MDROs recovered from any specimen collected >3 days post-admission, using laboratory data without patient’s clinical evaluation was conducted from Jan 2019 to Dec 2022 in Attikon & Tzaneio hospitals. MDROs included carbapenem-resistant (CR) Enterobacteriaceae (CRE), CR Acinetobacter baumannii (CRAB), CR Pseudomonas aeruginosa (CRPA), vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Adult inpatients hospitalized in ICUs or non-ICU wards participated in the study. Surveillance definitions of MDRO Laboratory-Identified (LabID) Event and MDRO Infection/Colonization Incidence Density Rate (IDR) were based on the CDC MDRO/CDI Module criteria (January 2023). Patient days and susceptibility data of isolated CRE were collected monthly. Incidence rate ratio (95% CI) was calculated to examine changes in rates from 2019 (pre-pandemic) to 2020, 2021 and 2022 (pandemic).

Results

During four years, 3,241 hospital-onset LabID Events, with no documented prior evidence of infection/colonization with the specific organism type, were recorded. The Infection/Colonization IDR for non-ICUs and ICUs was 0.59 and 6.69 per 1,000 patient days for CRE, 0.68 and 10.08 for CRAB, 0.19 and 1.41 for CRPA, 0.39 and 1.77 for VRE and 0.20 and 0.39 for MRSA, respectively. Compared to 2019, the CRE Infection/Colonization IDR raised significantly by 52% in 2020, 110% in 2021 and 146% in 2022 only in non-ICUs; non-significant increase was observed in ICUs. CRAB Infection/Colonization IDR increased constantly in non-ICUs after COVID-19 pandemic, but only during 2021 in ICUs. In CRE, KPC was the commoner carbapenemase (54%, 2019; 53%, 2020; 60%, 2021; 63%, 2022). CRPA infection/colonization significantly decreased during 2021 in ICUs (60%) but increased in 2022 in non-ICUs; VRE increased in 2022 in non-ICUs (61%) and MRSA remained unaltered.

Conclusion

MDRO Infection/Colonization IDR has further deteriorated during the pandemic with CRE and CRAB having leading role.

Disclosures

All Authors: No reported disclosures
2487. Which Extended-Spectrum β-Lactamase-Producing Enterobacterales Colonize the Gastrointestinal Tract of High-Risk Patients?
Authors: Stambaugh Haley , Lewis Shawna , Jacobs Emily B , Hareza Dariusz A , Bergman Yehudit , Cosgrove Sara E , Tamma Pranita , Simner Patricia J
Published: November 2023

Background

The epidemic of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E) continues to expand. ESBL-Es commonly colonize the intestinal tract and may propagate the spread of ESBL genes. However, the frequency at which ESBL production occurs in all Enterobacterales (including inducible AmpC-producers) is unknown. This study aims to define the epidemiology of third-generation cephalosporin resistant Enterobacterales (3GC-RE) colonization to understand their burden and contribution to ESBL spread in high-risk populations (e.g., ICU, oncology, transplant).

Methods

Surveillance cultures for 3GC-RE were performed by collecting perirectal swabs among high-risk populations at The Johns Hopkins Hospital. Isolates were identified by MALDI-TOF MS after recovery on 3GC selective chromogenic media. Antimicrobial susceptibility testing was performed using lyophilized broth microdilution panels following Clinical and Laboratory Standards Institute (CLSI) guidelines. 3GC-RE were characterized using the CLSI ESBL disk test among recommended Enterobacterales. For inducible AmpC-producing Enterobacterales, cefepime +/- clavulanic acid disk test was performed. Carbapenem-resistant Enterobacterales (CRE) were tested for carbapenemase-production using the modified carbapenem inactivation method (mCIM) and by the CARBA 5 lateral flow assay, if mCIM positive.

Results

Of 966 surveillance cultures, 99 (10%) were positive for 3GC-RE and 14 (1%) were positive for CRE. Almost all 112 (99%) rectal swabs had a single organism isolated while multiple organisms were isolated from 1 (1%). 114 bacterial isolates were recovered (Table 1). Of the 3GC-RE, 66 (58%) were ESBL-producers with Escherichia coli, Klebsiella pneumoniae and K. oxytoca being the most common ESBL-E. Additionally, 14 (12%) were CRE with K. pneumoniae, E. coli and Enterobacter cloacae complex being the most common CRE. Of CRE, 7 (50%) were carbapenemase producers with 4 (57%) KPC, 2 (29%) NDM and 1 (14%) KPC and NDM.

Conclusion

Colonization with 3GC-RE and CRE occurs in 10% and 1% of rectal swabs collected from high-risk patients, respectively. 58% of 3GC-RE were ESBL producers and ranged between 0-100% among 3GC-RE; including up to 33% from inducible AmpC producing Enterobacterales.

Disclosures

Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant Patricia J. Simner, PhD, Affinity Biosensors: Grant/Research Support|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|Entasis: Advisor/Consultant|GeneCapture: Stocks/Bonds|Merck: Advisor/Consultant|OpGen Inc: Board Member|OpGen Inc: Grant/Research Support|OpGen Inc: Honoraria|Qiagen Sciences Inc: Advisor/Consultant|Qiagen Sciences Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|T2 Biosystems: Grant/Research Support
2504. Online Clinician Education Results in Performance Changes in Clinical Practice Related to Hepatitis B Vaccination
Authors: Nair Arun S , Larkin Amy , Mehta Nimish
Published: November 2023

Background

This study examined whether online continuing medical education (CME/CE) focused on evidence-based best practices for implementing hepatitis B vaccination guidelines into clinical care would result in the adoption of new clinical practices.

Methods

Clinicians participated in an online, 30-minute CME/CE video discussion among experts with synchronized slides. Performance in the real world was assessed by inviting learners to complete a survey 30-60 days post-education, identifying practice changes and the degree to which clinicians experience barriers to those changes. For each possible practice, learners reported whether they were implementing for the first time or had modified it due to education, they were already doing it prior to education; or they were not doing it before or after education. They also indicated barriers they experience at least “some” of the time for each practice. The data were collected from 5/19/2022 to 10/24/2022.

Results

There were 44 learners consisting of PCPs, Diab/Endos, Ob/Gyns, Nurses, NPs and Pharmacists who completed the survey. Analysis showed that 100% of learners made a practice change or had practices reinforced due to education. Top 5 practice changes modified or implemented as a result of education included:

Some of the main barriers to implementing practice changes identified by the learners include:

Conclusion

The practice changes identified in this assessment provide a compelling evidence that participation in online CME/CE prompts adoption of changes in practice related to hepatitis B vaccination. Future education is needed to address the barriers identified in this assessment.

Disclosures

All Authors: No reported disclosures
2509. Association of Non-Alcoholic Fatty Liver Disease with HBV, HAV, and HEV Exposure
Authors: Vassilopoulos Stephanos , Vassilopoulos Athanasios , Benitez Gregorio , Kaczynski Matthew , Shehadeh Fadi , Kalligeros Markos , Mylonakis Eleftherios
Published: November 2023

Background

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), and hepatitis E virus (HEV) infection and NAFLD has not been elucidated. The National Health and Nutrition Examination Survey (NHANES) aims to assess the health and nutritional status of the population across the United States.

Methods

By using the 2017-2020 NHANES, we evaluated the age-adjusted prevalence of prior HBV, HAV and HEV infection among participants with NAFLD, as well as the age adjusted prevalence of NAFLD, high risk non-alcoholic steatohepatitis (NASH) and liver fibrosis among participants with prior HBV infection. We then performed multivariable logistic regression analyses using adjusted odds ratios (aOR) to examine the association of prior HBV, HAV and HEV infection with NAFLD, high risk NASH, and liver fibrosis.

Results

We identified 2565 individuals with anti-HBc serology results, 1480 unvaccinated participants with anti-HAV results, and 2561 participants with anti-HEV results. Among participants with NAFLD, the age-adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. The age-adjusted prevalence of NAFLD, high-risk NASH and fibrosis among participants with prior HBV infection was 33.59%, 3.36%, and 8.00%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD or high-risk NASH. Participants with anti-HBc and anti-HAV seropositivity were more likely to have significant fibrosis compared to participants with negative anti-HBc and anti-HAV serology [aOR: 1.53 (95% CI, 1.05 – 2.23) and 1.69 (95% CI, 1.16 – 2.47), respectively].

Age-adjusted prevalence of NAFLD, high-risk NASH and liver fibrosis among participants with positive anti-HBc serology

Adjusted odds ratio of prior viral hepatitis exposure

Conclusion

Participants with a history of HBV or HAV infection exhibit greater odds of significant liver fibrosis compared to those without HBV or HAV exposure. To limit disease-related outcomes, healthcare providers should prioritize vaccination efforts and use an individualized strategy for NAFLD in patients with prior viral hepatitis, including HBV or HAV infection.

Disclosures

Eleftherios Mylonakis, MD, PhD, BARDA: Grant/Research Support|Basilea: Advisor/Consultant|Chemic Labs/KODA Therapeutics: Grant/Research Support|Cidara: Grant/Research Support|Leidos Biomedical Research Inc./NCI: Grant/Research Support|NIH/NIAID: Grant/Research Support|NIH/NIGMS: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron Pharmaceuticals, Inc.: Grant/Research Support|SciClone Pharmaceuticals: Grant/Research Support
140. Follow-up Blood Cultures for Gram-Negative Bacteremia among Adults with Cancer
Authors: Haak David , Fong Karen , Spivak Emily S , Imlay Hannah
Published: November 2023

Background

Current evidence suggests that performing follow up blood cultures (FUBC) in patients with Gram-negative bacteremia (GNB) may not improve outcomes and can lead to unnecessary healthcare expenditure. However, studies often exclude more fragile patient populations, such as those with active malignancy. In a cohort of patients with active malignancy and GNB, we aimed to quantify the rate of performing FUBCs, the rate of positivity, and to compare characteristics of patients with and without positive FUBCs.

Methods

Patients admitted to University of Utah Health with active malignancy and GNB during 2019 were identified. Manual chart review was performed to collect demographics, clinical characteristics, management and outcome measures. Patients who had positive FUBC were compared to those with negative FUBC. Patients who died or went to comfort care only within 48h of admission were excluded.

Results

56 patients were identified. FUBCs were performed in 51 patients (70 FUBCs total) during the 4 days after initial positive blood culture. 4 FUBCs in 4 patients were positive. Of the positive FUBC, 2 (50%) were collected within 24 hours of the initial blood culture (Figure 1). 1 patient with a positive FUBC (25%) had not had source control achieved (Table 1).

90-day readmission (50% vs 34%) and recurrent GNB with the same organism (25% vs 8.5%) were higher in the positive FUBC group compared to the negative FUBC group. 90-day mortality (25% vs 28%) was similar between the two groups (Table 1).

Conclusion

In hospitalized patients with active malignancy and GNB, FUBC were performed frequently but the majority were negative. Of the positive FUBC, a significant proportion were either collected within 24 hours of starting active antimicrobials, limiting their significance. Prospective studies of standardized blood culture collection are needed to characterize the natural history of GNB and define when positive FUBC are clinically meaningful. These data suggest use of FUBC use could be reduced by limiting use to more than 24 hours after both appropriate antibiotic therapy is initiated and source control is achieved.

Disclosures

All Authors: No reported disclosures
2522. Antisense Antibiotics are Effective Against Pseudomonas aeruginosa Biofilm
Authors: Merville Paul J , Ray Garrett , Greenberg David E , Pybus Christine A , Helaibi Ibrahim
Published: November 2023

Background

P. aeruginosa (PA) causes severe infections in immunocompromised patients and is increasingly antibiotic resistant. In addition, the formation of biofilm by PA makes effective treatment difficult. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are novel antisense antimicrobials that are designed to target pathogens in a gene-specific way and prevent translation of protein. We have demonstrated in vitro and in vivo activity of lead PPMOs in PA; however, it remains unclear whether PPMOs remain active in the biofilm setting over time and if synergy can be achieved with traditional antibiotics.

Methods

P. aeruginosa (GFP-PAO1) was dosed with a rhodamine-labelled PPMO targeting acpP. Samples were fixed at different time intervals and imaged by fluorescent microscopy. A Pearson’s coefficient was recorded for each dose and time condition. Minimum biofilm eradication concentration plates were used to treat PA biofilm with acpP or rpsJ targeted PPMOs in daily dosing experiments. Fixed synergy assays were performed on mature biofilm via 24-hour Q8 dosing with PPMO, antibiotics or control. Biofilm burden was quantified by CFU enumeration.

Results

PPMOs co-localized with PA in a dose- and time-dependent fashion. Pearson coefficients increased from 0.0583 at the 30-minutes to 0.4118 and 0.4976 at the 3- and 5-hour time points respectively. In addition, biofilm reduction was dose-dependent. In daily dosing experiments, the 3’RXR4-AcpP PPMO resulted in a 5-log reduction in biofilm burden compared to control on day 7 [p< 0.0001]; the 5’RXR4-RpsJ PPMO resulted in a 5.5-log reduction in biofilm burden compared to no treatment control [p< 0.0001]. PPMOs incubated with tobramycin or aztreonam were found to have synergistic (FIC< 0.5) or antagonistic effects (FIC > 1) in biofilm and planktonic killing depending on the combination tested.

Conclusion

Lead PA PPMOs demonstrate dose and time-dependent biofilm eradication over multiple days of therapy. In addition, some PPMOs demonstrate synergy with other small molecule antibiotics that are used to treat certain patients with PA infections. PA PPMOs could be an innovative treatment modality for infection due to Pseudomonas.

Disclosures

David E. Greenberg, MD, University of Texas Southwestern Medical Center: Dr. Greenberg has numerous patents on PPMOs
2529. Population pharmacokinetic models for cefepime and enmetazobactam derived from pooled Phase 1 to Phase 3 clinical studies
Authors: Vollmer Jannik , Belley Adam , Velicitat Patrick , Machacek Matthias
Published: November 2023

Background

The investigational β-lactam/β-lactamase inhibitor combination of cefepime (FEP)/enmetazobactam (ENM) met criteria for non-inferiority and superiority compared to piperacillin/tazobactam in a phase 3 clinical trial of adult patients with complicated urinary tract infections (cUTI)/acute pyelonephritis (AP). In this study, a population pharmacokinetic (PK) model is presented that describes FEP and ENM plasma PK in adult cUTI/AP patients.

Methods

Plasma PK samples were analyzed from participants receiving FEP (n=588) and ENM (n=649) in three phase 1 (n=132), and single phase 2 (n=43) and phase 3 (n=488) clinical trials. Population PK parameters were assessed and the relationship between different covariates and model parameters were investigated. The effect of infection on disposition was assessed by testing disease covariates on fixed and random effects for all PK parameters.

Results

A two-compartment model with linear clearance of FEP (5.95 L/h) and ENM (7.68 L/h) from the central compartment best described the PK of both compounds. Common covariates for both compounds were de-indexed estimated glomerular filtration rate (eGFR), age, and body weight while ENM PK covariates also included cUTI infection and sex. Simulations showed that the only covariate requiring dose adjustment was renal function. The final model simultaneously described FEP and ENM plasma PK, which enabled estimates of the correlation of the random effects between PK parameters. Clearances and volumes of distribution (Vd) were strongly correlated within individuals between the two compounds (correlation coefficients >0.9). Variability was higher in cUTI patients although differences in mean ENM or FEP exposures between healthy subjects and cUTI patients were negligible. The total Vd was 16.9 L for FEP and 20.6 L for ENM. Clearance of both agents was found to depend on de-indexed eGFR (covariate coefficients ≥0.83), suggesting that renal filtration is the predominant clearance mechanism. The terminal elimination half-life was 2.2 h for FEP and 2.0 h for ENM.

Final population PK model population parameter estimates for cefepime and enmetazobactam determined from the pooled phase 1 to phase 3 clinical studies

Conclusion

The population PK models for FEP and ENM predict exposures in cUTI patients, including subjects with renal impairment. These models support Monte-Carlo simulations and target attainment estimations in adult cUTI/AP patients.

Disclosures

Adam Belley, PhD, Allecra Therapeutics SAS: Advisor/Consultant Patrick Velicitat, MD, Allecra Therapeutics SAS: Salary
2545. Impact of Early Dose Adjustment of Beta-Lactams in Patient with Septic Shock
Authors: Tawwater John C , Adams David T , Kaur Satwinder S , Ibragimova Nayle
Published: November 2023

Background

Effective antimicrobial dosing is crucial for survival in patient with septic shock. However, attaining therapeutic antimicrobial serum concentration is often problematic due to pathophysiological changes associated with critical illness. Antimicrobial concentrations can be decreased due to increased volume of distribution and augmented renal clearance. In addition, antibiotic doses are frequently adjusted per local renal dosing protocols based on creatinine clearance, resulting in suboptimal antibiotic exposures. The purpose of this study is to determine if unadjusted dosing of cefepime (CEF) and meropenem (MER) during the first 48 hours of septic shock improves clinical outcomes.

Methods

This is a retrospective observational cohort study comparing renally dose adjusted CEF and MER per institutional renal dosing protocol (pre-group, PRE) and unadjusted, full-dose CEF and MER (post-group, POST) (Figure 1). Adults aged 18-89 years with septic shock, initially treated with CEF or MER for at least 48 hours, and presenting with renal impairment are included. Patients receiving renal replacement therapies are excluded. The primary outcome is vasopressor-free days (VFD). Secondary outcomes are composite outcome of in-hospital mortality and hospice disposition, hospital length of stay (LOS), intensive care unit (ICU) LOS, and systemic inflammatory response syndrome (SIRS)-free days.Figure 1.Beta-lactam Dosing for Septic Shock - PRE and POST.

Results

Baseline demographic characteristics were similar between the groups with the exception of receipt of stress-dose steroids, which was significantly higher in PRE (p=0.019). The primary outcome of VFD was not significantly different between the groups, with a median of 9.33 days in PRE (n=40) and 9.54 days in POST (n=32) (Figure 2). The hospital LOS (PRE 12.5 days, POST 5.25 days, p=0.121), ICU LOS (PRE 5.5 days, POST 5 days, p=0.15), mortality, and SIRS-free days were not significantly different between the groups (Figure 3).Figure 2.Primary outcome - vasopressor-free days.Figure 3.Secondary outcomes - hospital LOS and ICU LOS.

Conclusion

Unadjusted beta-lactam dosing did not increase VFD, although the significantly higher use of stress-dose steroids in PRE could confound the result. There was no differences in secondary efficacy outcomes; however, an overall trend for shorter hospital LOS and ICU LOS in POST was observed.

Disclosures

All Authors: No reported disclosures