bluuebunny/crossref_metadata_2025_split huggingface dataset:
2772. Isolation and Characterization of Lytic Bacteriophages Targeting Clinical Isolates of genus Enterobacter
Authors: He Yanling , Zong Zhiyong 
Published: November 2023

Abstract

Background
Enterobacter strains are part of the human intestinal commensal microflora and important pathogens of hospital-acquired infections,such as bacteremia, lower respiratory tract infections, and urinary tract infections.
In an era of increasing antibiotic resistance, bacteriophage therapy is one way to combat bacterial pathogens considering its unique merits,such as self-replicating, self-limiting, safe, and highly specific.

Methods
Bacteriophages were isolated from water samples collected from Jinjiang River in Chengdu, PR China and sewage water from a hospital of the same city.Twenty carbapenem-resistant clinical isolates represent common species of Enterobacter were used to screen phages. Biological characteristics of all isolated phages were analyzed including host range determination with a panel of 50 Enterobacter strains and planktonic bacterial lysis assay of the host cells.All phages were subjected to genome sequencing.

Results
Twenty-three lytic bacteriophages were isolated and most of which belong to three families,Straboviridae(n=17). Two phages are respectively members of Autographiviridae(n=1) and Casjensviridae(n=1) as novel genera.Four phages could not be matched into any known classification.Most phages could lyse multiple isolates of genus Enterobacter as well as one isolate of genus Huaxiibacter.
The determination of lytic activity in vitro revealed that most phages are able to Inhibit bacterial growth for 4-24 hours.
taxonomic information of bacteriophages against Enterobacter
Partial lytic profiles of bacteriophages against Enterobacter
Planktonic cell lysis curve

Conclusion
Enterobacter-targeting phages has a wide lysis spectrum and some phages were significantly inhibited for an extended period of more than 24 hours.These results indicate the potential value of bacteriophages against Enterobacter infection in clinical treatment.

Disclosures
All Authors: No reported disclosures
2797. Antimicrobial Photodynamic Therapy (aPDT) Is Highly Effective Against Multidrug-Resistant HA- and CA- S. aureus Strains
Authors: Romo_Bernal Cristina P , Chavez Micah , Levengood Sheeny , Sabino Caetano , Loebel Nicolas G 
Published: November 2023

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) is often associated with multidrug-resistant (MDR) infections found in healthcare settings, resulting in 48,000 deaths in the US and 1.27 million deaths worldwide each year. S. aureus strains are a common component of nasal microbiota and can be disseminated by both patients and healthcare workers, posing a substantial hospital-acquired infection risk. Antimicrobial photodynamic therapy (aPDT) combines the use of a photosensitizer (PS) with a specific wavelength of light to induce photochemical reactions lethal to a broad spectrum of microbes, without resistance induction. The objective of this study was to demonstrate the efficacy of aPDT against clinically-relevant multidrug-resistant S. aureus strains using a commercially-available photosensitizer formulation (SteriwaveTM, Ondine Biomedical Inc., Vancouver, BC).
Resistance profile of MRSA strains

Methods
The MRSA strains used in this study included confirmed resistance to: cefoxitin, clindamycin, erythromycin, levofloxacin, mupirocin, oxacillin, penicillin, rifampicin, novobiocin, tetracyclines, trimethoprim/sulfamethoxazole, gentamicin, chloramphenicol, ciprofloxacin, moxifloxacin, linezolid, tedizolid quinupristin/dalfopristin and mupirocin. aPDT was carried out by exposing planktonic suspensions of each strain to photosensitizer formulations containing either 0.01% MB or SteriwaveTM (0.01% MB and 0.25% chlorhexidine gluconate in an aqueous excipient base). Illumination was performed at 670 nm, 150 mW/cm2 for 60 s (9 J/cm2). Samples were serially diluted and plated on TSA for CFU counting

Results
Relative to untreated controls, aPDT resulted in a minimum reduction of 3log10 (99.9%) against all MRSA strains tested, with the commercial SteriwaveTM formulation producing an average of 10X greater kills than aqueous methylene blue under the same illumination parameters.

Conclusion
aPDT is highly effective against a variety of clinically-relevant multidrug-resistant S. aureus strains in 60 s of treatment. The technique represents a promising alternative to antibiotics in healthcare systems where antimicrobial resistance strategies are important

Disclosures
Nicolas G. Loebel, PhD, ONDINE Biomedical Inc.: Board Member|ONDINE Biomedical Inc.: Employee|ONDINE Biomedical Inc.: Stocks/Bonds
2800. Carbapenem Resistant Enterobacteriaceae bloodstream infections in children from Latin America & Caribbean region: systematic review and meta-analysis
Authors: Ruvinsky Silvina , Jimena Carla , Roel Macarena , Brizuela Martin , Portillo Victoria Maria , Naranjo-Zuniga Gabriela , Ulloa-Gutierrez Rolando , Ciapponi Agustin , Comande Daniel , Bardach Ariel 
Published: November 2023

Abstract

Background
Systematic reviews about the burden and use of resource related to Carbapenem Resistant Enterobacteriaceae bloodstream infections (CRE-BI) in children from Latin America and Caribbean (LAC ) is scarce.

Methods

Objectives
To analyze demographic, epidemiological, clinical, use of resource and microbiological data from CRE-BI in LAC

Methods
A systematic review following Cochrane methods, PRISMA/MOOSE statements was performed (PROSPERO 2022 CRD42022352504). We searched all databases (MEDLINE, Embase, LILACS, SciELO, CENTRAL, CINAHL, Cochrane Library, WHO Database and relevant websites) from 1/1/2012 to 9/30/2022. Independent selection, data extraction, and risk of bias assessment (RoB) were performed with COVIDENCE. Types of study included; observational/surveillance/experimental/quasi-experimental. Population: Inpatients &lt; 19 years old, with CRE-BI. Outcomes: age, underlying conditions, previous (invasive procedures, colonization, antibiotic treatment, PICU). treatment and use of resources. Statistical analysis: proportion meta-analyses applying an arc-sine transformation and RoBTo, We conducted proportion meta-analyses and applied arc-sine. R studio was used

Results
25/858 screened studies included for full text assessment with 243 patients were included. The most represented countries were Brazil (30%), Colombia (26%) and Argentina (22%). Median age was 34.5 months (IRQ 14-85). Predominant resistance mechanisms: KPC (96%), NDM (58%), OXA (27%). Pool proportion were: Male 55%. Underlying conditions 100% (immunocompromised host 84%), Previous Colonization with CRE was 42% (CI95% 13-78) and broad spectrum antibiotic used was 88% (CI95% 46-98%), most commonly carbapenems 84% (CI95% 72-91%) Bacteremia secondary to intra-abdominal infection was 80%. Combination antimicrobial treatment was 96% (CI95% 22-100%). Median length of stay 22.5 (IQR 22-30 days). Overall case fatality ratio was 48% (IC95% 27-69%).

Conclusion
CRE-BI cause morbidity and mortality mainly in pediatric population with underlying disease in LAC region. Considering its high impact in public health, it's mandatory to establish adequate policies and programs to improve antimicrobial stewardship.

Disclosures
All Authors: No reported disclosures
2804. Azole versus echinocandin combination therapy for the treatment of invasive mucormycosis: A case series
Authors: Shah Meera , Gibbons Emily A , Gutierrez G Christina , Reveles Kelly 
Published: November 2023

Abstract

Background
Mucormycosis is a rare and aggressive mold infection with an all-cause mortality of 54%. Treatment for mucormycosis has historically consisted of high dose liposomal amphotericin B (LAmB) as monotherapy. Recent data has emerged studying combination therapies; however, this data is conflicting, and the benefit of combination therapy remains unclear. This case series aims to explore different combination therapies utilized for the treatment of mucormycosis and their effect on mortality.

Methods
We report 17 cases of proven or probable mucormycosis managed with combination therapy for at least 48 hours at University Hospital between March 2020 and November 2022.

Results
The median age of patients was 60 years old (range 21-74), and 11 patients were male (64.7%), with a median BMI of 27.8 kg/m2. Of the 17 patients, all patients (100%) were Hispanic, nine patients (53%) had diabetes and two patients (12%) were lung transplant recipients. The most common infection site was rhino-orbital (6/17; 35%) and surgery was performed on 11 patients (64.7%) after a median of two days after hospital admission. All 17 patients received LAmB with an average initial dose of 5.13 mg/kg/day (range 2.9-6.4 mg/kg/day). All patients received combination therapy with either posaconazole (6/17; 35.2%), micafungin (4/17; 23.5%), or triple therapy (7/17; 41.2%). Duration of combination therapy was a median six days (range 2-21 days). Five of the 17 patients (29%) died of mucormycosis-related complications. Mortality observed in patients receiving combination therapy is as follows: micafungin combination (4/4; 100%), posaconazole combination (5/6; 83%), and triple therapy (0/7; 0%).

Conclusion
Mucormycosis is an aggressive fungal infection with high morbidity and mortality that requires immediate recognition, urgent intervention, and appropriate antifungal dosing. Combination therapy with micafungin maybe associated with higher mortality compared to posaconazole or triple therapy. In this cohort, combination may be associated with lower mortality that previously documented but further investigation is required to determine optimal combination treatment for invasive mucormycosis.

Disclosures
Kelly Reveles, PharmD, PhD, Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Honoraria
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

Abstract

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

Abstract

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

Abstract

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 &lt; 30d, co-diagnosis where antibiotics were indicated, hospital discharge &lt; 7d, scheduled urological procedure &lt; 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

Abstract

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 &lt; 0.001), be in an intensive care unit (70.4% vs. 65.7%, p &lt; 0.001), and receive vasopressors (26.6% vs. 23.1%, p &lt; 0.001). Older adults with cUTI had a longer median length of stay (8 vs. 7 days, p &lt; 0.001), were more likely to be discharged to nursing homes (40.7% vs. 18.2%, p &lt; 0.001), and had a higher median cost of hospitalization ($18,191.62 vs. $15,800.76, p &lt; 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 &lt; 0.001) or cefepime (31.2% vs. 28.0%, p &lt; 0.001) though less likely to receive an aminoglycoside (9.5% vs. 12.1%, p &lt; 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

Abstract

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 &gt; 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