bluuebunny/crossref_metadata_2025_split huggingface dataset:
1661. Evaluation of Cefazolin &lt; 3 g vs. 3 g Treatment Doses for Cellulitis in Patients Who Weigh ≥ 120 kg within a Large, Community Health System
Authors: Gens Krista , Wankum Michael , Hirsch Elizabeth B , Gagnon Brandon 
Published: December 2022

Abstract

Background
Cefazolin 3 g is recommended for obese patients weighing &gt; 120 kg preoperatively; however, there is no available evidence to suggest 3 g for treatment dosing of cefazolin in this population. This study aims to provide the first clinical data of its kind on the efficacy and safety of high-dose cefazolin in the treatment of cellulitis in obese patients using a modified Desirability of Outcomes Ranking (DOOR) methodology.

Methods
This is a multi-center, retrospective cohort study including adults weighing &gt; 120 kg at the time of admission who received ≥ 48 hours of cefazolin monotherapy for cellulitis. Patients were gathered in a 3:1 ratio between the &lt; 3 g dosing (standard-dose; SD) and 3 g dosing (high-dose; HD) groups. Patients were excluded if they had co-infections, bacteremia, bilateral lower extremity cellulitis, or if they received &gt; 48 hours of concomitant antibiotics. The primary endpoint of efficacy and safety as determined by modified DOOR criteria was compared between obese patients who received HD and those who received SD between 1/1/2021 and 12/31/2021. The DOOR is a patient-centered methodology that uses combined efficacy and safety endpoints to help inform better clinical decision-making.

Results
A total of 68 patients were included; 51 received SD and 17 received HD cefazolin. There were no differences in mean age nor baseline kidney function or severity of illness between groups. The median patient weights were 140.6 kg and 160 kg for the SD and HD groups, respectively (p = 0.07). Patients achieving clinical success (resolution of cellulitis within 10 days or clinical improvement upon discharge) was higher in the HD vs SD group (70.6% vs 41%; p=0.036) (Figure 1).

Conclusion
Cefazolin 3 g was associated with higher clinical success in patients &gt; 120 kg with cellulitis. Further study is necessary to confirm these results.

Disclosures
Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, Melinta: Advisor/Consultant|MeMed: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support.
1448. Socio-demographic and clinical characteristic of Tuberculosis in Tor Vergata Hospital, Rome: a 9-years analysis
Authors: Benedetta Rossi 
Published: December 2022

Abstract

Background
Tuberculosis (TB) represents one of the major global health problems worldwide. Italy is a low-incidence country for TB with a prevalence of 23% of extrapulmonary forms (EPTB). Migrants coming from high TB incidence country might modify local epidemiology.

Methods
We conducted a retrospective, single-center observational study including data from patients with an active TB diagnosis, admitted to the Infectious Diseases Department of Tor Vergata Hospital, Rome, from 2013 to 2021

Results
The study included 210 patients with a median age of 38 years (IQR 36-46), 77% were male, 74% were not Italians (31% Africans,26% East-Europeans,11% Asian and 6% Latin Americans)
28% of patients were immunocompromised: 5.7% tested positive for HIV, 4.7% were on immunosuppressive treatment with anti-TNF drugs, 4.7% had onco-hematological diseases, 15.7% had severe malnutrition. PPD, performed in 90 patients, resulted positive in 77; QuantiFERON-TB Gold (QTF), performed in 187 patients, resulted positive in 149, indeterminate in 9 and negative in 29 patients. 43% of patients presented with EPTB, of whom 38 had lymph node TB, 24 bone TB, 20 pleural TB, 17 abdominal TB, 9 central nervous system TB and 23 were disseminated TB (≥3 systems involved). EPTB forms, compared to pulmonary TB (PTB), were significantly more common in males (p=0.027), of younger age (p&lt; 0.001), from Africa and Asia (p&lt; 0.01). Immunosuppression was not significantly associated with EPTB. Lymphocytes and monocytes absolute count were significantly lower in patients with EPTB, compared to PTB (Fig. 1). Lymphocyte subpopulations were analyzed in 89 patients, showing a significantly lower CD4 count in patients with EPTB, compared to PTB (p=0.006) (Fig. 2). QTF tube 2 titer was higher in the EPTB forms (p=0.024), no association was found with QTF tube 1 (p=0.069) and QTF mitogen (p=0.118) with TB localization. (Fig.3) QTF negativity rate was higher in patients with EPTB (p=0.063).
Lymphocytes and monocytes in extrapulmonary TB (E) and pulmonary TB (P)
Analysis of lymphocytes subpopulations in extrapulmonary TB (E) and pulmonary TB (P)
Analysis of Quanti-FERON titer in extrapulmonary TB (E) and pulmonary TB (P)

Conclusion
In our cohort, there was a high prevalence of EPTB (43%), mainly diagnosed in young, otherwise healthy men from high-endemic areas, highlighting the connection of EPTB with socio-demographic determinants. Although QFT negativity rate was higher in EPTB patients, a prudent interpretation of QFT might be needed in patients with high suspicion of EPTB.

Disclosures
All Authors: No reported disclosures.
1454. Describing the Epidemiology of Nosocomial Respiratory Viral Infections (RVIs) at an Academic Medical Center
Authors: Rathod Shardul N , Nam Hannah H , Ison Michael G 
Published: December 2022

Abstract

Background
Nosocomial respiratory viral infections (NRVI), transmitted from infected visitors or healthcare providers to patients, lead to significant morbidity and mortality. This study describes the epidemiology of nosocomial Influenza (flu) and Respiratory Syncytial Virus (RSV) at an academic medical center from 2009 to 2018.

Methods
After institutional review board (IRB) approval, data on NRVI was collected from our Enterprise Data Warehouse and primary chart review. A nosocomial infection was defined as a positive result of flu or RSV collected ≥ 72 hours after admission between April 2009 and March 2018.

Results
There were 93/1,317 (7.1%) nosocomial flu cases and 76/617 (12.3%) nosocomial RSV cases detected during the study period (see Table 1). Flu and RSV were first detected at a median of 6.8 and 8.4 days, respectively, after admission. Patients with nosocomial flu and RSV were more likely to have a cancer diagnosis, be a stem cell transplant recipient within one year, and have undergone chemotherapy in the past 30 days (see Table 2).
Few nosocomial transmissions (15%) occurred outside the usual winter respiratory viral season (December through March, see Figure 1). Table 1Distribution of Nosocomial RVIsTable 2Underlying Medical Conditions Among Patients with Nosocomial and Community-Acquired RVIFigure 1Distribution of nosocomial RVIs over time assessing for transmission seasonality

Conclusion
Nosocomial infections account for 7% of hospitalized flu cases and 12% of hospitalized RSV cases. Infection is more common among patients at high risk of complications. Effort needs to be directed at approaches to reduce the risk of nosocomial transmission of RVI. Future studies are needed to assess the impact of interventions, such as universal masking, on the rate of nosocomial infections.

Disclosures
Michael G. Ison, MD MS, GlaxoSmithKlein: Grant/Research Support|Pulmocide: Grant/Research Support|Viracor Eurfins: Advisor/Consultant.
1455. Diagnosis and Testing of Travel-Associated Dengue, Alameda County, California – 2019
Authors: Andemel Naissem L , Heaton Dustin T , Shemsu Munira , Marusinec Rachel , Trivedi Kavita K 
Published: December 2022

Abstract

Background
Dengue is an acute febrile infection with one of the four dengue viruses that are transmitted through the bite of mosquitoes. It is a communicable disease reportable to local health departments under Title 17 of the California Code of Regulations via CalREDIE (California Reportable Disease Information Exchange), which receives positive Electronic Lab Reports or Confidential Morbidity Report forms when Dengue infection is strongly suspected. Alameda County is among the top 5 jurisdictions in California for travel-associated Dengue infection reports. In order to inform best practices for diagnosis and treatment, we explored Dengue reports to Alameda County pre-pandemic.

Methods
CalREDIE data for possible Dengue infections from 2019 were categorized according to CSTE’s Dengue Virus Infections 2015 Surveillance Case Definition into cases (probable and confirmed) or non-cases (suspect and not a case). Univariate and bivariate analysis were conducted in R.

Results
In 2019, 83 reports of possible Dengue infections were received; 23 met the case classification criteria for confirmed (n=8) or probable (n=15) cases. Most (61%) of the cases were reported between the months of June and October (Figure 1). All cases were symptomatic after travel to an area where Dengue is endemic, notably India (39%), Mexico (17%) and the Philippines (13%). Of the cases, 70% visited the Emergency Department and 48% were hospitalized due to concerns for severe dengue (Table 1). Cases had &gt; 4 times the odds of being hospitalized (Odds Ratio = 4.89, 95% Confidence Interval = 1.63-14.7, p = 0.01) compared to non-cases. 78% of the cases were tested for Dengue within 1 week from symptom onset, but of those, only 39% had a PCR or antigen test while 83% had an IgM test and 78% had an IgG test (Table 2). Figure 1Table 1:Patient Characteristics by CalREDIE Case Resolution Status of 2019 Dengue ReportsTable 2:Laboratory Testing Practices for 2019 Cases with Labs within 7 days of Symptom Onset

Conclusion
More outreach efforts are needed to educate health care providers on providing timely and adequate testing to travelers and improve diagnosis of travel-associated Dengue. Based on pre-pandemic surveillance in Alameda County, Dengue should be strongly suspected in patients who present with an acute febrile illness and history of travel to Dengue endemic areas such as India, Mexico, and the Philippines. Health care providers suspecting Dengue should test with either PCR or antigen tests within a week of symptom onset.

Disclosures
All Authors: No reported disclosures.
1464. Real-World (RW) Utilization Pattern of Letermovir in Adult Cytomegalovirus Seropositive Allogeneic Hematopoietic Stem Cell Transplant (HCT) Recipients: A Multicenter Retrospective Cohort Study from the European Society for Blood and Marrow Transplantation (EBMT) Registry
Authors: Styczynski Jan , Tridello Gloria , Knelange Nina , Wendel Lotus , Xhaard Alienor , Cutini Ilaria , Chiusolo Patrizia , Franke Georg-Nikolaus , Kraus Sabina , Raval Amit D , Merchant Sanjay , de la Camara Rafael 
Published: December 2022

Abstract

Background
Letermovir (LET) prophylaxis in CMV seropositive (R+) allogeneic (allo) HCT recipients was approved in 2017 based on a Phase 3 randomized clinical trial (RCT) demonstrating lower rates of CMV infection, disease, and all-cause mortality among LET treated participants. While RCTs demonstrate causal effects between treatments and outcomes, RW data answer practical aspects of utilization such as time to initiation of LET and duration of use. The objective of this study was to assess LET RW utilization pattern in adult CMV R+ recipients of allo-HCT in a large cohort of multiple centers in Europe participating in the EBMT registry.

Methods
A retrospective observational cohort design was used to examine the RW utilization patterns of LET among CMV R+ of an allo-HCT in France, Germany & Italy. Inclusion criteria were CMV R+ recipients &gt;18 years who received LET for any reason between Jan 1 2018- Dec 31, 2020 and had data available for at least until 100 days post-HCT.

Results
In this interim analysis, 138 allo-HCT recipients (52% male) with median age 55 years (range 19-72) received LET as primary prophylaxis. Donor/recipient CMV serostatus was D+/R+ 64% D-/R+ 36%. Donor type was 65% unrelated, 20% mismatched relative, 15% sibling. Standard conditioning was used in 56% and reduced-intensity in 44%. Peripheral blood stem cells were the source in 89%. T-cell depletion was performed in 48%. All centers followed WHO standardization guidelines for CMV viral load assay by PCR. Viral load was determined at time of LET initiation in 86% patients. Oral (PO) only LET formulation was used in 98% of patients (median 2 days post HCT; LET was initiated prior to HCT in 3% of the recipients). Centers indicated that intravenous (IV) formulation was administered only if patients could not tolerate PO. The median duration of PO use was 98 days. LET dose was 240 mg (86%) mostly in patients receiving cyclosporine, 480 mg (9%) or sequentially 240/480 mg (5%).

Conclusion
Some differences were observed in this interim RW LET analysis compared to the phase 3 RCT. Notably, patients began LET at a median of D+2 post HCT (compared to D+9 in the trial), and 98% received only PO LET (as compared to 26.5% receiving IV LET in the trial). Further studies are needed to determine drivers of LET utilization in RW settings.

Disclosures
Jan Styczynski, MD, PhD, MSD: Honoraria Amit D. Raval, PhD, Merck and Co., Inc.: Employee of Merck|Merck and Co., Inc.: Stocks/Bonds Sanjay Merchant, PhD, Merck & Co., Inc.: Stocks/Bonds Rafael de la Camara, MD, MSD: Honoraria.
1671. Activity of Imipenem/Relebactam and Comparators Against Gram-Negative MDR and DTR Pathogens from Patients with Respiratory and Bloodstream Infections – SMART United States 2018-2020
Authors: Lob Sibylle , Hackel Meredith , Siddiqui Fakhar , Bauer Karri A , DeRyke Charles A , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: December 2022

Abstract

Background
Gram-negative pathogens with multidrug resistance (MDR) or difficult-to-treat resistance (DTR) are increasingly common, resulting in limited treatment options. These resistant pathogens are often isolated from the respiratory tract or bloodstream and can result in significant patient morbidity and mortality. Imipenem/relebactam is a combination of imipenem with relebactam, a β-lactamase inhibitor of class A and C β-lactamases. We evaluated the activity of imipenem/relebactam and comparators (imipenem, meropenem, piperacillin/tazobactam, cefepime, ceftazidime, levofloxacin, and amikacin) against gram-negative MDR and DTR isolates that were collected from patients with lower respiratory tract (RTI) or bloodstream infections (BSI) in the United States (US).

Methods
In 2018-2020, 24 clinical labs participated in the global SMART surveillance program in the US, and each collected up to 100 consecutive aerobic or facultative gram-negative pathogens per year from patients with RTI and 50 from BSI. MICs were determined using CLSI broth microdilution and interpreted with CLSI breakpoints.

Results
MDR isolates were found among 13.5% of collected P. aeruginosa (n=2018), 11.9% of E. coli (n=1952), 13.1% of K. pneumoniae (n=1080), 24.1% of E. cloacae complex (n=460), 19.7% of K. aerogenes (n=304), and 6.1% of S. marcescens isolates (n=304); DTR isolates were found among 7.1%, 0.1%, 2.4%, 1.5%, 0%, and 0.8%, respectively. Imipenem/relebactam was active against 61% of MDR P. aeruginosa, 43-53 percentage points higher than the studied comparator β-lactams, and against 49% of DTR P. aeruginosa, which were nonsusceptible to all studied commonly used β-lactams and levofloxacin (Table). Imipenem/relebactam was also active against 87-100% of MDR Enterobacterales, including against 97% of MDR K. pneumoniae, 18-96 percentage points higher than the studied comparator β-lactams, and against 85% of DTR K. pneumoniae.

Conclusion
Based on these in vitro data, imipenem/relebactam represents a promising treatment option in the US for patients with RTI or BSI caused by highly resistant gram-negative pathogens that pose substantial treatment challenges.

Disclosures
Fakhar Siddiqui, MD, MBA, Merck & Co., Inc.: employee|Merck & Co., Inc.: Stocks/Bonds Karri A Bauer, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Charles A. DeRyke, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds.
1678. Activity of mecillinam against urinary tract clinical isolates from the United States during 2017-2020 including isolates resistant to comparator antibiotics and multi-drug resistant isolates
Authors: Hawser Stephen , Kothari Nimmi , Monti Federica , Henriksen Anne Santerre 
Published: December 2022

Abstract

Background
Mecillinam is a first-in-class amidinopenicillin antibiotic, being the only β-lactam to exert its antibacterial activity through exclusive binding to penicillin-binding protein 2. Pivmecillinam is the oral prodrug of mecillinam recommended as a first-line therapy by the Infectious Disease Society of America guidelines for uncomplicated urinary tract infections (uUTIs) and is approved for the treatment of uUTI in Europe and Canada though not yet in the USA. To support the clinical development of mecillinam and pivmecillinam in the USA for the treatment of cUTI and uUTI, this study investigated the activity of mecillinam compared with other antibiotics against Enterobacterales isolates from patients with UTI in the US during 2017-2020

Methods
A total of 3303 Enterobacterales clinical isolates from UTIs from hospitals throughout the USA during 2017-2020 were tested. MIC tests were performed by agar dilution in line with CLSI susceptibility testing standards.

Results
Overall, susceptibility was highest for fosfomycin (97.1% susceptible) and mecillinam (94.9% susceptible). Against isolates resistant to ceftriaxone, ciprofloxacin, fosfomycin, nitrofurantoin and trimethoprim/sulfamethoxazole susceptibility to mecillinam was high with 89.6 %, 90.9 %, 82.4 %, 86.7 % and 93.6 %, respectively. Only fosfomycin exhibited similar activity to mecillinam. The most active antibiotics against MDR Enterobacterales were fosfomycin (86% susceptible) and mecillinam (79.2 % susceptible). Of the 288 MDR Enterobacterales, the majority were E. coli (n = 128) and K. pneumoniae (n = 103). The most active agents against MDR E. coli and MDR K. pneumoniae were fosfomycin and mecillinam that had susceptibilities of 93.8 % and 92.2 % and 79.6 % and 72.8 %, respectively.

Conclusion
Mecillinam exhibited promising activity against the majority of Enterobacterales tested. The drug was notably active against isolates resistant to antibiotics in routine clinical use and notably was similarly active against many MDR isolates. The data from our study strongly support the clinical utility of mecillinam and pivmecillinam in the USA for the treatment of cUTI and uUTI.

Disclosures
Anne Santerre Henriksen, PhD, UTILITY therapeutics Ltd: Advisor/Consultant.
1665. Potential underreporting of treated patients using a Clostridioides difficile testing algorithm that screens with a nucleic acid amplification test
Authors: Guh Alice , Winston Lisa Gail , Johnston Helen , Basiliere Elizabeth , Olson Danyel M , Fridkin Scott , Goodenough Dana , Wilson Christopher , Watkins Jasmine , Korhonen Lauren C , Gerding Dale N 
Published: December 2022

Abstract

Background
U.S. laboratories are increasingly using a two-step algorithm to diagnose Clostridioides difficile infection (CDI) that starts with a nucleic acid amplification test (NAAT), and if positive, reflexes to a toxin enzyme immunoassay. Here only a NAAT+/toxin+ result is reported to the Centers for Disease Control and Prevention’s (CDC) National Healthcare Safety Network (NHSN) as a CDI laboratory-identified (LabID) event, but limited data suggest that NAAT+/toxin- results may also be considered CDI by clinicians. To explore this discrepancy, we compared the characteristics and treatment of NAAT+/toxin- and NAAT+/toxin+ patients.

Methods
CDC’s Emerging Infections Program (EIP) conducts population-based CDI surveillance. A case was defined as a positive C. difficile test in a person aged ≥1 year with no positive tests in the prior 8 weeks. We included cases detected by this two-step algorithm in 5 EIP sites during 2018–2020 that underwent a full chart review. Multivariable logistic regression models adjusting for age, sex, race, comorbidities, epidemiologic classification, and CDI therapy were used to compare CDI-related complications (i.e., toxic megacolon, ileus, colectomy, or intensive-care unit stay) and recurrence between the two groups.

Results
Of 1250 NAAT+ cases, 897 (72%) were toxin- and 353 (28%) were toxin+. Lower percentages of toxin- versus toxin+ cases were aged ≥65 years (42% vs 58%; P&lt; 0.0001), had diarrhea (779/831 [94%] vs 329/338 [97%]; P=0.01), or had white blood cell counts ≥15,000 cells/μL (183/811 [23%] vs 132/321 [42%]; P&lt; 0.0001). CDI therapy was given to 683/882 (77%) toxin- versus 338/349 (97%) toxin+ cases (P&lt; 0.0001). In multivariable analysis, toxin- status was protective for recurrence (adjusted odds ratio [aOR], 0.49; 95% confidence interval [CI], 0.32–0.74) but not for CDI-related complications (aOR, 1.00; 95% CI, 0.64–1.56).

Conclusion
NAAT+/toxin- cases were less likely to have recurrence but were as likely to have CDI-related complications as NAAT+/toxin+ cases. More than twice as many potentially unreported NAAT+/toxin- cases were treated than the number of reported NAAT+/toxin+ treated cases. Use of this two-step algorithm likely results in underreporting of treated CDI cases to NHSN.

Disclosures
Scott Fridkin, MD, Pfizer: Grant/Research Support Dale N. Gerding, MD, Destiny Pharma plc.: Advisor/Consultant.
1666. Sources and Preventability of Hospital-onset Bacteremia and Fungemia in the United States: Evaluation of a Potential Healthcare Quality Measure
Authors: Leekha Surbhi , Robinson Gwen , Jacob Jesse T , Fridkin Scott , Shane Andi L , Sick-Samuels Anna , Milstone Aaron , Nair Rajeshwari , Perencevich Eli N , Puig-Asensio Mireia , Kobayashi Takaaki , Mayer Jeanmarie , Lewis Julia , Bleasdale Susan C , Wenzler Eric , Mena Lora Alfredo J , Baghdadi Jonathan , Schrank Gregory M , Nadimpalli Gita , Harris Anthony 
Published: December 2022

Abstract

Background
Hospital-onset bacteremia and fungemia (HOB) is being proposed as a potential healthcare quality measure due to its clinical significance, objectivity, and ease of detection. However, information is lacking on sources of HOB and the proportion and types of cases considered preventable.

Methods
We evaluated sources and potential preventability of HOB cases at 12 hospitals using retrospective chart review. HOB was defined as a positive blood culture &gt;= day 4 (admission date=day 1) for one or more organisms. Stratified sampling of cases by commensal and noncommensal organisms was used. Infectious disease physicians determined the source of HOB and rated preventability from 1-6 (1=definitely preventable to 6=definitely not preventable) using a previously validated guide. Ratings of 1–3 were collectively considered potentially preventable and 4–6 likely not preventable.

Results
We evaluated sources and potential preventability of HOB cases at 12 hospitals using retrospective chart review. HOB was defined as a positive blood culture &gt;= day 4 (admission date=day 1) for one or more organisms. Stratified sampling of cases by commensal and noncommensal organisms was used. Infectious disease physicians determined the source of HOB and rated preventability from 1–6 (1=definitely preventable to 6=definitely not preventable) using a previously validated guide. Ratings of 1–3 were collectively considered potentially preventable and 4–6 likely not preventable.

Conclusion
Gastrointestinal and endovascular sources account for a large majority of noncommensal HOB cases. A high proportion of noncommensal HOB cases are likely not preventable. The presence of non-preventable events should be considered when using HOB as a quality measure. Approaches to identifying the subset of preventable noncommensal HOB events should be explored.

Disclosures
Scott Fridkin, MD, Pfizer: Grant/Research Support Andi L. Shane, MD, MPH, MSc, International Scientific Association for Probiotics and Prebiotics (ISAPP): travel and lodging to attend international meeting to deliver a presentation, June 2022 Aaron Milstone, MD, Merck: Grant/Research Support Rajeshwari Nair, MBBS, PhD, Vertex Pharmaceuticals: Salary.