bluuebunny/crossref_metadata_2025_split huggingface dataset:
2515. Evaluation of the Equivalency of the Oxoid Sulbactam-Durlobactam (10/10µg) Antimicrobial Disc to the CLSI M07 Broth Microdilution Frozen Reference Method
Authors: Hajek Katie L , Lovatt Amie J , Bhalerao Shilpa , Khan Nagina , Staats Dylan T , Hendrix Megan M , Holliday Nicole M , Knapp Cindy C 
Published: November 2023

Abstract

Background
Sulbactam-durlobactam is an intravenous (IV) investigational drug that is a combination of an IV β-lactam antibiotic (sulbactam), and a novel broad-spectrum IV β-lactamase inhibitor (durlobactam). Sulbactam-durlobactam (SUD) is being developed for the treatment of serious infections caused by Acinetobacter spp., including multidrug-resistant (MDR) strains, and carbapenem-resistant strains. A study was conducted to evaluate the performance and reproducibility of the new Thermo Fisher™ Oxoid™ sulbactam/durlobactam 10/10 μg (SUD20) antimicrobial disc (Thermo Fisher Scientific, Basingstoke, UK) in comparison to the CLSI M07/M100 broth microdilution (BMD) frozen reference method (Thermo Fisher Scientific, Oakwood Village, OH).

Methods
Oxoid SUD20 discs were tested alongside BMD frozen reference panels for the clinical and challenge portions of this study. Two lots of SUD20 discs were utilized to show inter-lot reproducibility as read by three users over three consecutive days of testing. Isolates tested included: 227 Acinetobacter baumannii, 5 Acinetobacter calcoaceticus, 5 Acinetobacter pittii, 7 Acinetobacter nosocomialis. Quality control organisms included A. baumannii NCTC 13304, and Escherichia coli ATCC 25922 using ranges provided in the CLSI M100 document. All isolates were tested in accordance with CLSI M02/ CLSI M07/M100 and EUCAST methodologies.

Results
A categorical agreement of 98% was achieved when comparing the SUD20 disc to the BMD method. Reproducibility results showed 99.3% within-reader and between-reader agreement within 3 mm of the modal value of the combined results. QC results were within the stated limits on each day of testing for each batch, and reader.

Conclusion
The SUD20 disc, when compared to the BMD method, demonstrated an equivalent level of performance against clinical breakpoints as proposed by Entasis Therapeutics. The high categorical agreement obtained by the SUD20 disc indicates that this is an acceptable method for susceptibility testing of sulbactam-durlobactam for isolates of Acinetobacter spp.

Disclosures
All Authors: No reported disclosures
2604. Contact With School-Aged Children is a Major Risk Factor for Pneumococcal Colonization in Older Adults
Authors: Wyllie Anne L , Yolda-Carr Devyn , Hislop Maikel , Mbodj Sidiya , Kennedy Harold J , McLaughlin Molly , Wurst Loren , Waghela Pari , Peno Chikondi , Alexander-Parrish Ronika , Arguedas Adriano , Gessner Bradford D , Weinberger Daniel M 
Published: November 2023

Abstract

Background
Important questions remain about the role of older adults in driving transmission of pneumococcus in the community. This is a critical question for understanding the potential indirect effects of using pneumococcal conjugate vaccines (PCVs) in older adults. For non-institutionalized individuals, the most likely source of adult-to-adult transmission is in the household. The goal of this study was to characterize the dynamics and risk factors for acquisition of pneumococcus in older adults.

Methods
We designed a longitudinal study to sample adults &gt; 60 years of age living in the same household (New Haven, CT), and without younger contacts residing in the household. Saliva samples and questionnaires regarding social behaviors and health status were obtained every 2 weeks for a period of 10 weeks. DNA extracted from culture-enriched saliva was tested using qPCR for pneumococcus genes piaB and lytA.

Results
Across the two study seasons (November 2020-August 2021, November 2021-September 2022), 184 individuals from 93 households were sampled and completed all 6 visits. Overall, 31/184 (16.8%) individuals were colonized on at least one time point based on qPCR detection of piaB. Two individuals were colonized at 6/6 time points, and two others were colonized at 5/6 time points during the 10-week sampling period. In 7/93 (7.5%) households, both members were colonized, though not necessarily at the same time point. Pneumococcal colonization was substantially higher among individuals who had contact with children &lt; 18 years as compared to those with no recent contact with children (9.4% vs 2.3%). Participants who reported recent contact with &lt; 5 year olds and 5-9 year olds had particularly elevated prevalence (14.3%; 13.0%, respectively).

Conclusion
Pneumococcal acquisition related to adult-to-adult transmission is low. Contact with pre-school and young school-aged children was the most important factor that influenced acquisition rates of pneumococcus among older adult households.

Disclosures
Anne L. Wyllie, PhD, Co-Diagnostics: Board Member|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support Ronika Alexander-Parrish, RN, MAEd, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Adriano Arguedas, Medical director, Pfizer: Emplyee|Pfizer: Stocks/Bonds Bradford D. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Daniel M. Weinberger, PhD, GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
2642. Multipathogen Antigen Test Kit (MAK-5) – Distribution and Frequency of Viral Respiratory Diseases in Germany among Volunteers in the VACCELERATE Registry
Authors: Nacov Julia A , Salmanton-Garcia Jon , Joisten Carolin , Többen Christina , Fleig Julian , Rochel Lisa , Cremer Louise , Pana Zoi Dorothea , Schmitt Heinz-Josef , Stemler Jannik , Cornely Oliver A 
Published: November 2023

Abstract

Background
Currently, SARS-CoV-2 is the predominant viral respiratory pathogen. However, during winter season other viruses may cause acute respiratory infection (ARI). Most cases of non-severe ARI are not systematically tested, thus, distribution and epidemiology of these viruses is largely unknown.
VACCELERATE is the EU funded consortium dedicated to vaccine research, running a volunteer registry and promoting clinical studies.

Methods
Adult registered subjects were invited to participate. Postal address was collected to allow sending of the MAK-5 test kit (BioTeke Corporation (Wuxi) Co., Ltd., Wuxi, Jiangsu, China). The availability of low-cost, sensitive and specific rapid tests detecting 5 pathogens (ADV, influenza viruses A and B, RSV, SARS-CoV-2) from one respiratory sample allowed us to conduct a feasibility study on their relative contribution to the burden of disease (BoD) outside any medical setting. Participants were instructed to use the test if respiratory symptoms were present for at least 24h. Test results and information on related symptoms and vaccinations were self-reported by e-mail. Underlying diseases were known from initial registration.

Results
Between 07-Dec-2022 and 01-May-2023, we processed test results from 1036 (52.1%) of 1990 participants. Including co-infections (N=18; 4.7%), we detected 384 infections: 178 (46.4%) SARS-CoV-2, 59 (32.8%) 104 (27.1%) RSV and 74 (19.3%) influenza A virus. ADV infection was detected in 10 (2.6%) volunteers and influenza B virus in 6 (1.6%). A total of 98.8% of tests yielded valid results, while 12 (1.2%) tests were invalid (negative control). While RSV was the most frequently detected virus in the first week of assessment (calendar week (CW) 49), there was a shift to Influenza A virus in CW 50, followed by a SARS-CoV-2 peaks in CW 51/22, 05/23, and 08/23.
CW49/2022-CW18/2023

Conclusion
This type of study allows assessment of the BoD by ARI pathogens before medical attention is sought and provides insights into the course of the annual (winter) infection waves down to a local level. Frequency of detected viruses varied over time. While SARS-CoV-2, RSV and influenza A virus were detected frequently, ADV and influenza B virus infections were rare.

Disclosures
Heinz-Josef Schmitt, n/a, VACCELERATE: Advisor/Consultant Jannik Stemler, -, Ministry of Education and Research (BMBF): Grant/Research Support Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds
2702. A Case Series of Kidney Transplant Recipients on Belatacept with CMV Infection in a Single Academic Center
Authors: Feller Fionna , Cohen Elizabeth , Marvin Jennifer , Virmani Sarthak , Malinis Maricar F 
Published: November 2023

Abstract

Background
Cytomegalovirus (CMV) infection has been increasingly observed among kidney transplant recipients (KTR) on belatacept for immunosuppression. Clinical outcomes of CMV infection among KTR on belatacept are not well described. We aimed to evaluate further in this case series from a single center.

Methods
We performed a retrospective study of KTR on belatacept who developed CMV infection and were hospitalized between the period of 1/1/2017-12/31/2022. Data collected were: demographics, transplant and CMV parameters, allograft outcomes, and co-infection. Descriptive statistics was performed.

Results
Of the 1,468 KTR, 387 received belatacept and have been hospitalized. Ten of the 387 (2.6%) had CMV infection. Among the 10, 60% were female and 20% were black. Median age was 59 years (range 32-78) and median time from transplant to first CMV infection was 6 months (range 1-228). Five had CMV DNAemia and 5 had CMV disease. Among the 5 with CMV DNAemia, 1 was CMV D+/R- and 4 was CMV R+. Of the 5 with CMV disease, 2 were CMV D+/R- and 3 were CMV R+. Corresponding clinical outcomes are reported in Figure 1.
Belatacept administration was uninterrupted in 7/10 KTR. Of these 7, the highest median peak and the longest duration of CMV DNAemia were seen in the CMV D+/R- only. CMV infection relapse (3/7), allograft rejection (1/7), and allograft loss (1/7) occurred in those with uninterrupted belatacept infusion. Bacterial co-infections occurred in 6/10 KTR. All survived &gt; 90 days after CMV diagnosis. KTR with interrupted belatacept (n=3) were eventually changed to alternative regimen of azathioprine, tacrolimus, and everolimus.Table 1.Patient demographicsFigure 1.CMV clinical outcomes

Conclusion
High risk KTR who received uninterrupted belatacept at time of CMV infection were observed to have the high level and prolonged duration of CMV DNAemia. Renal allograft rejection/loss and CMV relapse were also observed with uninterrupted belatacept administration regardless of CMV donor serostatus. This limited data suggests that KTR with either CMV D+/R- or CMV R+ may have poor clinical outcomes with continued belatacept administration in the setting of CMV infection. Prospective, multi-center studies are needed to better assess the impact of belatacept management during CMV infection.

Disclosures
All Authors: No reported disclosures
2713. Risk factors and clinical presentation of Herpes Simplex Virus Encephalitis in cancer patients
Authors: Kodama Rich , Kamboj Mini 
Published: November 2023

Abstract

Background
Herpes Simplex Virus Encephalitis (HSVE) can have lifelong sequelae. Presentation can be nonspecific in cancer patients. Cerebrospinal fluid testing may be falsely negative early in illness [1]. New immune-based or targeted radiation (RT) modalities may change risk, incidence of HSVE in cancer patients.

Methods
Retrospective study at Memorial Sloan Kettering Cancer Center (MSK). Review of records of patients with CSF meningitis/encephalitis (ME) PCR panels from 8/1/2016 to 7/31/2022. All unique patients who received brain RT at MSK during those dates were used to calculate incidence rates.

Results
2749 patients had 5497 CSF analyses with ME panel. Of these, 12 tests from 10 patients showed HSV-1 or -2; 1 patient had relapsing HSVE and 3 positive HSV2 tests each done at least 6 months apart.
Table 1 shows 10 patients with HSVE. 8 had solid tumors, 6 with receipt of chemo- or immunotherapy within 30 days. All solid tumor patients with HSVE had brain RT; 6 received steroids. 1 patient with relapsing HSVE was on immune checkpoint inhibitor (ICI). 4/8 patients with MRIs (Table 2) lacked typical findings; 4/8 patients with EEGs had focal temporal seizure activity. CSF pleocytosis was absent in 4/10 cases. 5 patients had residual deficits. 4 died due to progression of disease.
Incidence of HSVE with brain radiation was 2.6/10,000 patient-years.

Conclusion
General population incidence of HSVE ranges from 1-4 per million population per year [2]. Those receiving cancer treatment and brain RT have elevated HSVE risk. We found the risk after brain RT is much higher: 2.6/10,000 person-years. Only 1 of 10 patients in our series made a full recovery.
Other key findings include:
Limitations:

Disclosures
Mini Kamboj, MD , ASCO: speaker fee|Medscape: speaker fee|MJH life sciences: speaker fee|Regeneron: Advisor/Consultant|Web md: speaker fee
2752. Outcomes of Patients with Stenotrophomonas maltophilia infections treated with Cefiderocol in PROVE (Retrospective Cefiderocol Chart Review) Study
Authors: Marcella Stephen , Friedman Bruce , Cai Bin , Verardi Stefano , Gozalo Laurence , Nguyen Sean T 
Published: November 2023

Abstract

Background
Gram-negative (GN) bacterial resistance remains an urgent global health problem. Cefiderocol (CFDC) has activity against Stenotrophomonas maltophilia (SM) isolates. PROVE is an ongoing international, retrospective study of CFDC use in GN infections (GNI). This report gives the first description of patients infected with SM as the primary infection treated with CFDC.

Methods
Eligible patients received ≥ 72 hours of CFDC during routine clinical practice attributed to a primary SM infection. Patient characteristics, hospital course, and treatment patterns are described. Outcomes of clinical cure and 30-day all-cause mortality (ACM) were examined by infection site, pathogen phenotype, patient characteristics, and treatment patterns. Clinical cure is defined as resolution or improvement in infection signs and symptoms without later relapse.

Results
As of March 2023, 54 patients were treated with CFDC for a primary SM infection at 39 sites in the US and Europe. The median age was 59 years; 72.2% were male. Chronic pulmonary disease (27.8%), moderate or severe renal disease (18.5%), and COVID-19 (14.8%) were the most frequent comorbidities. Respiratory infections were most common (n=38, 70.4%). 72.2% of patients were given CFDC in an ICU setting. Mechanical ventilation and vasopressor support were required in 57.4% and 40.7%, respectively.
31 (57.4%) of SM infections were polymicrobial GNI, 21 (67.7%) being Pseudomonas aeruginosa (Table 1). No SM culture was resistant to CFDC when tested (N=15). The median time from positive culture sample to CFDC therapy was 6 days (interquartile range 4–10). Most (68.5%) of patients had the first dose of CFDC 5 days or more after the index culture was taken (Table 1). CFDC was used as monotherapy in 42.6%. Targeted use with or without preceding failure of other GN antibiotics was 88.9%.
Clinical cure and 30-day ACM were 64.8% and 18.5%, respectively. Monomicrobial and polymicrobial infections had similar clinical cure rates (65.2% and 64.5%), but 30-day ACM was greater for monomicrobial infections (30.4% vs. 9.7%) (Table 1).

Conclusion
Patients with SM treated with CFDC in a real-world setting had mostly respiratory infections. Over half of SM infections were polymicrobial but had similar rates of clinical cure as those that were monomicrobial.

Disclosures
Stephen Marcella, MD, MPH, Shionogi, Inc: contracting work for Shionogi, Inc Bruce Friedman, MD, Shionogi: Honoraria Bin Cai, MD, PhD, Shionogi Inc.: Shionogi employee Stefano Verardi, MD, Shionogi B.V.: Employee Laurence Gozalo, PhD, Shionogi, Inc: Analyst Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee
2764. Experience with dalbavancin in a pediatric hospital
Authors: Leon Maria Deza , Murphy Mark 
Published: November 2023

Abstract

Background
Due to its long half-life allowing for once-weekly dosing, dalbavancin has become an appealing option for the treatment of infections that require prolonged antibiotic courses. While studies have shown non-inferiority of dalbavancin compared to conventional antibiotic regimens, there is limited information regarding its use in the pediatric population. We describe the experience with dalbavancin use in a large pediatric hospital.

Methods
Children and young adults who were seen at Cincinnati Children’s Hospital between the period of July 1st, 2019 and December 31st, 2022 and received antibiotic therapy with Dalbavancin were included in this study. We reviewed the patient’s demographic data, laboratory findings including microbiologic data, clinical course, response to treatment and outcomes. Treatment failure was defined as no response or worsening after initial improvement. Clinical response was also evaluated at day 90 after end of therapy.

Results
We identified 26 children and young adults who received dalbavancin between July 1st 2019 and December 31st 2022 (Table 1). Ages ranged between 6 months and 22 years. Most common indication was osteomyelitis. Side effects were rare and included flushing and transient vision loss, which was later diagnosed as ocular migraine. Seven patients (26.9%) had treatment failure at 90 days, including 33.3% and 18.2% of patients with and without comorbidities, respectively. Ages of patients with treatment failure ranged from 6 months to 20 years. Five of them showed initial improvement during the first week after therapy but required an antibiotic switch due to worsening. Time to failure from first dose of dalbavancin ranged from 10 to 35 days. Of all 7 patients who failed therapy, four had no recovered organisms, two had MRSA and one had MSSA. One patient with no initial recovered organism grew Pseudomonas aeruginosa on a repeat culture.
Characteristics of patients who received dalbavancin between July 1st, 2019 and December 31st,2022

Conclusion
While our population was small, a high treatment failure rate was seen when using dalbavancin, particularly in patients with comorbidities. More data is needed to evaluate its performance in the pediatric population and clinicians should be thoughtful about deciding who is a good candidate for dalbavancin therapy.

Disclosures
All Authors: No reported disclosures
2849. Doxycycline for the Treatment of Urinary Tract Infections
Authors: Zheng Tina , Mehta Monica , Stilwell Allison , Demenagas Nicholas 
Published: November 2023

Abstract

Background
The 2010 IDSA uncomplicated cystitis and pyelonephritis guideline does not recommend doxycycline as an oral option for the treatment of urinary tract infections (UTI). Doxycycline is reported to have 35-60% urinary excretion. Small prospective cohort studies from the 1960-1980s suggest favorable clinical and microbiological outcomes. This multicenter, retrospective study aimed to describe the effectiveness and safety of doxycycline to treat UTIs.

Methods
Patients aged ≥ 18 years who received at least one dose of doxycycline for the treatment of UTI from September 1, 2020 to August 31, 2022 were included. Patients with a positive chlamydia/gonorrhea result, suspected concomitant sexually transmitted infections, asymptomatic bacteriuria, or with urine culture isolates resistant to tetracyclines were excluded. Treatment success was defined as resolution of urinary symptoms on day 3 and the last day of treatment for patients who received their entire doxycycline course while inpatient. Secondary outcomes included clinical recurrence, microbiological success and recurrence, and adverse drug events. Patients who had a partial inpatient doxycycline course met treatment success criteria if they did not re-present for medical care with UTI symptoms within 7 days post-treatment completion.

Results
Seventeen patients were evaluated. Patients were older with a median age of 65 years, and 47% reported antibiotic allergies. Most patients had cystitis (65%), though four patients had pyelonephritis (24%). The most common organism isolated was Klebsiella pneumoniae (24%). Resistance to third-generation cephalosporins, carbapenems, and levofloxacin was 79%, 14%, and 53%, respectively. The median duration of doxycycline treatment was 8 days. Treatment success for the complete inpatient treatment group and the partial inpatient treatment group was 75% (6/8) and 89% (8/9), respectively. Only one patient (6%) experienced syncope attributed to doxycycline.

Conclusion
Despite the limited urinary penetration of doxycycline, this study suggests that it may be an alternative option for treatment of UTIs, particularly in patients with a lack of oral options due to allergies or resistant organisms.

Disclosures
All Authors: No reported disclosures
370. The comparison of adverse events in combination with double beta-lactam antimicrobials: Ampicillin plus Ceftriaxone and Ampicillin/Cloxacillin with bloodstream infections
Authors: Ishikawa Kazuhiro , Kobayashi Daiki , Mori Nobuyoshi 
Published: November 2023

Abstract

Background
Double beta-lactams are used to treat infective endocarditis, but the incidence rate of adverse events is unclear. We aimed to compare the incidence rates of adverse events of ampicillin(ABPC) versus ABPC plus ceftriaxone(CTRX) and ABPC/MPIPC(cloxacillin).

Methods
We retrospectively included adult bacteremia patients admitted to St. Luke's International Hospital and received ABPC, ABPC plus CTRX, and ABPC/MPIPC between 2004 and 2022. We excluded patients on hemodialysis, those with missing data, those who used more than three beta-lactam antimicrobials, and beta-lactam other than ABPC, CTRX, or ABPC/MPIPC. All statistical analysis was done using IBM SPSS.

Results
We included 280, 59, and 43 patients for ABPC, ABPC plus CTRX, and ABPC/MPIPC, respectively. There were significant differences in median age(70.8 [standard deviation: SD 16.6], 64.3[16.7], 56.6[17.5]), male sex(62.1%, 47.5%, 72.1%), qSOFA ≥2 (23.1%, 64.4%, 41.9%), admission in an intensive care unit(6.4%, 40.7%, 14.0%), mechanical ventilation (5.4%, 23.7%, 20.9%), use of vasopressor (10.4%, 32.2%, 23.3%), administration of vancomycin (7.5%, 27.1%, 41.9%) or clindamycin (19.6%, 23.7%, 44.2%) for more than three days, hepatic dysfunction (AST: 42.6[81.5], 120.4[493.0], 54.1[68.5], ALT: 33.1[35.9], 98.2[380.0], 46.6[67.6], anemia(Hgb: 10.8[2.1], 11.6[2.4], 11.9[2.8] and thrombocytopenia (PLT: 203.5[105.0], 154.8[115.0], 255.9[159.7]) on admission. There were significant differences in AKI (9.0%, 12.3%, 30.2%), treatment duration (13.9 [12.1] days, 9.1 [8.7] days 29.0 (19.2) days, and duration of hospitalization 34.1[31.1] days, 48.3 [50.4] days, 51.6 [32.5] days, but no difference in 30 days mortality (4.3%, 6.8%, 2.3%) and 90 days mortality (8.2%, 13.6%, 7.0%). Kaplan-Meier analysis showed no significant difference between ABPC and CTRX plus ABPC in AKI, but there was a significant difference between ABPC and ABPC/MPIPC(figure 1, 2). The hazard ratio of ABPC/MPIPC for AKI was 1.572(95% confidence interval, 1.067-2.315)(figure 3).Figure 1Percent of non-AKI between ABPC and ABPC plus CTRXAbbreviation: AKI, acute kidney injury; ABPC, ampicillin; CTRX, ceftriaxoneFigure 2Percent of non-AKI between ABPC and ABPC/MPIPCAbbreviation: AKI, acute kidney injury; ABPC, ampicillin; MPIPC, cloxacillin

Conclusion
Double beta-lactam therapy with ABPC plus CTRX may be relatively safe, but careful follow-up is needed for platelet count and hepatic function. On the other hand, ABPC/MPIPC has a significantly higher incidence of AKI compared to other antimicrobials.
Factors associated with AKI
Abbreviation: AKI, acute kidney injury; ABPC, ampicillin; MPIPC, cloxacillin; CI, coincidence interval

Disclosures
All Authors: No reported disclosures