bluuebunny/crossref_metadata_2025_split huggingface dataset:
2127. In vitro Activities of Ceftaroline and Comparator Agents against Bacterial Pathogens Frequently Causing Community-Acquired Respiratory Tract Infections in Patients from a Global Population: ATLAS Surveillance Program 2018-2021
Authors: Hackel Meredith , Stone Gregory , Sahm Daniel F 
Published: November 2023

Abstract

Background
Community-acquired bacterial pneumonia (CABP) is a frequent cause of patient morbidity and mortality. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are frequent etiologic agents of CABP. Ceftaroline fosamil is a parenteral cephem approved treatment of patients with CABP caused by S. pneumoniae (including cases with concurrent bacteremia), methicillin-susceptible Staphylococcus aureus (MSSA), H. influenzae, and some species of Enterobacterales. In this study we report the in vitro activity of ceftaroline and comparators against isolates from community-acquired respiratory tract infections (CARTI) collected through a global surveillance program.

Methods
Clinically relevant, non-duplicate, isolates cultured from respiratory specimens by clinical laboratories in 54 countries in 2018-2021 were collected by the ATLAS Surveillance Program central laboratory (IHMA, Schaumburg, IL, USA). Community-acquired infections were defined as those from patients &lt; 48 hours in hospital. In total, 7,886 isolates of S. pneumoniae, H. influenzae, M. catarrhalis, MSSA, and methicillin-resistant S. aureus (MRSA) were tested. The isolates (n/percent of total) originated from Asia/South Pacific (1,893/24.0%); Europe (4,283/54.3%); Latin America (671/8.5%); Middle East/Africa (659/8.4%); and North America (Canada only) (380/4.8%). Ceftaroline and comparator agent MICs were determined by CLSI M07 broth microdilution methodology. MICs were interpreted using 2023 CLSI M100 MIC breakpoints.

Results
The in vitro activity of ceftaroline and comparator agents is summarized in the table. Greater than 99% of S. pneumoniae and 100% of MSSA were susceptible to ceftaroline, including penicillin-nonsusceptible S. pneumoniae based on a dosage of 600 mg every 12h. Sixty-two (9.6%) MRSA were ceftaroline-susceptible-dose-dependent (MIC 2-4 µg/mL) based on a dosage of 600 mg every 8h administered over 2h, with the majority from (n) Thailand (9), S. Korea (7), and China (6). Four isolates, from S. Korea (2), China (1), and Ukraine (1) were resistant to CPT (MIC of ≥8 µg/mL). 99.6% of H. influenzae were susceptible to ceftaroline.

Conclusion
Ceftaroline demonstrated potent in vitro activity against current pathogens associated with CABP from a global collection.

Disclosures
Meredith Hackel, PhD, Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Gregory Stone, PhD, Pfizer: Stocks/Bonds Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation
2905. Development of a Desirability of Outcome Ranking (DOOR) for Skin Infection Clinical Trials
Authors: Miller Loren G , Phan Tran Donna , Flores Evelyn A , Liu Honghu , Weidmer Beverly A , Kupferwasser Deborah , Boyle Mary G , Williams Pluscedia , Zhou Linyu , Huang Yilan , Evans Scott R , Fritz Stephanie A 
Published: November 2023

Abstract

Background
Infectious disease clinical trials treatment outcomes have almost exclusively been dichotomized into cure and failure. The novel Desirability of Outcome Ranking (DOOR) method uses a hierarchical ordinal outcome of intervention outcomes. DOOR measures are more sensitive for detection of differences between groups compared to dichotomous outcomes and thus can lead to dramatic reduction of the number of required trial participants. Additionally, the DOOR design addresses patient-centered outcomes that are ignored in traditional infectious diseases clinical trial outcomes. DOOR methodology has neither been used for skin and soft tissue infection (SSTI) clinical trial outcomes nor incorporated patients about their experiences with SSTIs.

Methods
We conducted 6 focus groups of providers, patients, and parents at two medical centers in Los Angeles and St. Louis. Focus groups were composed of clinicians who treat SSTIs (n=2), patients who had SSTIs (n=3) and parents of children who had an SSTI (n=1). Focus group participants were given a series of SSTI clinical scenarios with various outcomes and asked to rank these 10 outcomes on a numerical scale from most to least desirable. We fitted 4 CART (classification and regression tree) models for overall, provider, patient and parent responders, respectively.

Results
In total, we had 62 focus group participants (24 providers, 30 patients, and 8 parents). Overall, the most desirable outcome was no complications (rank value = 1.0), followed by rash or nausea (mean rank values = 4.9 - 5.1), diarrhea or recurrent infection (= 5.9), dizziness or stomach ache (= 6.1 - 6.2), recurrent drainage procedure or household transmission (= 7.0 - 7.2), and hospitalization (= 8.3). Least desirable outcomes differed between groups, with providers choosing hospitalization while patient/parents indicated household transmission. Variance in outcome desirability differed more widely between patients compared to providers. (Figure).

Conclusion
We developed a DOOR outcome for SSTIs clinical trials that incorporates both provider and patient perspectives. This metric could be tested in clinical trials as a means to reduce sample size and to incorporate patient-focused outcomes.

Disclosures
Loren G. Miller, MD MPH, ContraFect: Grant/Research Support|GSK: Grant/Research Support|Medline: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support
2138. In Vitro Susceptibility of Recent Clinical Isolates of P. aeruginosa and Enterobacterales to Imipenem or Meropenem Alone or in Combination with Sulbactam-Durlobactam
Authors: McLeod Sarah , Carter Nicole , Moussa Samir , Miller Alita 
Published: November 2023

Abstract

Background
Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination in development for the treatment of infections caused by Acinetobacter spp., including multidrug resistant strains. ATTACK was a global, active-controlled Phase 3 trial conducted to evaluate the efficacy and safety of SUL-DUR vs. colistin for patients with Acinetobacter infections. Both arms were dosed on a background of imipenem/cilastatin to treat co-infecting Gram-negative pathogens. Here, the in vitro activity of carbapenems with or without SUL-DUR added against P. aeruginosa (PA) or Enterobacterales is presented.

Methods
Broth minimal inhibitory concentrations (MICs) for single, double, and triple combinations of sulbactam, durlobactam and imipenem or meropenem were determined following CLSI methodologies. Two different sets of isolates were tested: 104 molecularly characterized clinical isolates and 69 co-infecting baseline pathogens from the ATTACK trial.

Results
Against 55 Enterobacterales isolates, the MIC90s of imipenem and meropenem were reduced from 32 and &gt;32 μg/ml to 2 μg/ml in the presence of durlobactam. Against 49 carbapenem-resistant P. aeruginosa, addition of durlobactam reduced the imipenem MIC90 8-fold from 32 to 4 μg/ml and the meropenem MIC90 from 64 to 16 μg/ml. Of the 39 co-infecting pathogens from ATTACK, 30 (43%) were carbapenem non-susceptible (8 PA, 21 Klebsiella pneumoniae and 1 Proteus mirabilis). Addition of durlobactam restored imipenem susceptibility to 83% (N = 25) and meropenem susceptibility to 70% (N = 21) of these isolates. No antagonism was observed for any durlobactam combination tested. The addition of sulbactam had no effect on the antibacterial activity of either carbapenem -/+ durlobactam added for any of the isolates in this study.

Conclusion
The addition of durlobactam restored the in vitro antibacterial activity of imipenem and meropenem against a majority of carbapenem-resistant Enterobacterales and P. aeruginosa clinical isolates, while the addition of sulbactam had no effect on any combination tested. These results indicate that durlobactam has the potential to restore carbapenem activity against these organisms when present in Acinetobacter polymicrobial infections.

Disclosures
Sarah McLeod, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds|Innoviva Specialty Therapeutics: Stocks/Bonds Nicole Carter, MS, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds Samir Moussa, PhD, Innoviva: Stocks/Bonds|Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds Alita Miller, PhD, Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds
2149. In vitro Activity of Aztreonam-avibactam and Comparator Agents Against Carbapenem-Resistant Enterobacterales With and Without Carbapenemases, ATLAS Global Surveillance Program, 2017–2021
Authors: Wise Mark G , Arhin Francis , Sahm Daniel F 
Published: November 2023

Abstract

Background
The investigational β-lactam/non-β-lactam β-lactamase inhibitor combination aztreonam-avibactam (ATM-AVI) is active in vitro against CRE isolates, including MBL-producers, as well as those co-producing serine β-lactamases of Class A, C, and some class D types. This study evaluated the in vitro activity of ATM-AVI and comparators against carbapenemase- and non-carbapenemase-producing CRE collected globally from 2017−2021 as part of the ATLAS surveillance program.

Methods
85,990 non-duplicate, clinically relevant Enterobacterales isolates were collected from 258 medical centers located in 56 countries worldwide (excluding N. America and China). Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2023 breakpoints. ATM-AVI was tested at a fixed concentration of 4 mg/L avibactam. A tentative ATM-AVI pharmacokinetic/pharmacodynamic (PK/PD) susceptible MIC breakpoint of ≤ 8 mg/L was applied for comparison purposes. Organisms with meropenem MIC &gt;1 mg/L and Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with aztreonam or ceftazidime MIC &gt;1 mg/L were screened for β-lactamase genes by PCR and Sanger sequencing.

Results
In total, 5,473 isolates were identified as CRE based on resistance to meropenem. ATM-AVI demonstrated potent in vitro activity against the CRE, with 99.3% of isolates (MIC90, 1 mg/L) inhibited at ≤8 mg/L (Table). ATM-AVI inhibited 99.5% of the carbapenemase-positive CRE, including 99.1% of the MBL-carriers (n=2,375) and 99.8% of serine-carbapenemase carriers (n=2,675) at ≤8 mg/L. Activity was somewhat reduced against the 441 CRE without detected carbapenemases as 96.3% (MIC90, 4 mg/L) of the isolates were inhibited at ≤8 mg/L aztreonam-avibactam. Amikacin was the most active comparator, although &lt; 50% of each subgroup was susceptible at the CLSI breakpoint.

Conclusion
Based on MIC90 values and the preliminary PK/PD breakpoint, ATM-AVI demonstrated potent in vitro activity against CRE, including MBL- and serine carbapenemase-carrying isolates. As limited therapeutic options presently exist for treating infections caused by CRE, further development of this agent appears warranted.

Disclosures
Mark G Wise, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation
2177. Characterization of community-acquired methicillin-resistant Staphylococcus aureus isolated from patients with skin and soft tissue infections in selected health facilities, in Kenya
Authors: Njenga John N 
Published: November 2023

Abstract

Background
Colonization of the skin, mucus membrane, and nose of humans by Staphylococcus aureus (S. aureus) is more common than infection. The lack of proper microbiological surveillance systems in Africa may underestimate the burden of Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), while little is known about its incidence. In Kenya, there is a paucity of data on prevalence and circulating CA-MRSA strains.

Methods
Cross-sectional study design was employed with a sample size of 228 wound swabs from community-acquired skin and soft tissue infections, collected from 5 AMR surveillance sites in Kenya. S. aureus isolation, identification, and antimicrobial susceptibility tests were carried out according to standard bacteriology methods. Molecular characterization for MRSA isolates was performed by whole genome sequencing.

Results
Descriptive and inferential statistics were computed using the R program. Total S. aureus isolated was 29.38 % while MRSA isolation varied within study sites, with a CA-MRSA prevalence of 1.8 %. Phenotypic resistance observed did not match genotypic resistance for some isolates. Resistance mostly reported in nosocomial infections and resistance to reserved antibiotics was observed, which raises concern. Mutations within resistance genes, Inducible-Macrolide-Lincosamide-Streptogramin b resistance (MLSBi), 23S ribosome resistance and also erythromycin resistance by efflux pump was observed. Staphylococcal chromosomal cassette mec (SCCmec) type IV was the most prevalent while the sequence types (STs) obtained were ST 30, 8 and the novel STs 7460 and 7635. Only one isolate had intact mecA and its regulatory genes, but still conferred methicillin resistance. IS 1272 was detected in mecA regulatory genes.

Conclusion
The resistance patterns observed in this study further highlight the burden of antimicrobial resistance in community isolates of S. aureus. There is need for more research on CA-MRSA within Antimicrobial resistance (AMR) surveillance in Kenya in order to better understand the molecular epidemiology as well as the drivers of resistance

Disclosures
All Authors: No reported disclosures
2192. Impact of an Antibiotic Transitions of Care Program Utilizing Outpatient Retail Pharmacists
Authors: Bouchard Jeannette , Orvin Alison , Cochran Adam , Taylor Kelly , Eldridge Renee , Habibfeisal Azima 
Published: November 2023

Abstract

Background
For many common community infections shorter durations of therapy are equivalent to longer durations and can be completed in 7 days or less. There’s a growing need to target antibiotic prescribing at discharge and reduce total length of antibiotic therapy. The objective of this study was to determine the impact of a transitions of care (TOC) program with outpatient retail pharmacists.

Methods
This retrospective cohort study included patients ≥18 years discharged with antibiotic prescriptions to the hospital’s outpatient pharmacy from August 2021 to June 2022. Prescriptions included had to be for the following infections: community acquired pneumonia (CAP), acute COPD exacerbation, uncomplicated urinary tract infections, complicated urinary tract infections, pyelonephritis, and cellulitis. Patients were excluded if they were immunocompromised, had an Infectious Diseases consult, a Urology consult, or had bacteremia at any point during admission. The intervention group contained prescriptions reviewed by outpatient pharmacists utilizing a protocol, the control group prescriptions were unreviewed. The primary outcome was adherence to protocol durations of therapy. Secondary outcomes include average outpatient prescription duration, number of recommendations made, and number of recommendations accepted.

Results
323 patients were screened for inclusion, 162 in the intervention group and 160 in the control group. Seventy-nine (49%) and 76 (48%) were included in the intervention group and control groups, respectively. Overall, 59% were female, mean age was 67, most frequent indications were CAP (36%) and cellulitis (22%). Adherence to protocol durations were 75% and 50% in the intervention and control groups, respectively (p&lt; 0.01). The average outpatient prescription duration was 4 days for the intervention group and 4.5 days for the control group. 40 (51%) of prescriptions in the intervention group had recommendations made and 28 (70%) were accepted. Most recommendations were for CAP (38%).
Average Total Antibiotic Duration and Maximum Allowed Duration Per Protocol

Conclusion
The TOC program with outpatient pharmacists had better adherence to protocol durations of therapy than control and acceptance rates were high among recommendations made. This program showcases a potential avenue to improve outpatient antibiotic durations.

Disclosures
All Authors: No reported disclosures
2196. Private Practice Dentists Answer the Dental Antibiotic Stewardship "Call to Action" with a Grassroots Initiative
Authors: Goff Debra A , Mangino Julie E , Stoner Jason , Goff Douglas 
Published: November 2023

Abstract

Background
In the US, 90% of dentists work in private practice (PP). We aim to describe how infectious diseases (ID) antibiotic stewardship (AS) experts collaborated with dentists to provide dental AS education.

Methods
Fifteen PP dentists completed a study conducted in 2021 by an ID-AS pharmacist and physician assessing their antibiotic use to identify AS opportunities. After learning dental AS from ID–AS experts, these dentists optimized and significantly decreased their antibiotic use. An AS “call to action” was launched in Sept. 2021 on how to expand our education to additional dentists to optimize antibiotic prescribing further. Dentists recommended ID-AS experts provide dental AS education to their long standing established local and national dental study club networks and other dental continuing education (CE) venues. Education focused on 5 areas: decreasing antibiotic use and durations, eliminating clindamycin and quinolones, incorporating shared decision making with patients, reviews of evidence based studies, and penicillin allergic patient management. Attendees were asked 3 questions prior to each lecture; 1. Have you heard of the term dental AS?; 2. Do you use clindamycin for penicillin allergic patients? 3. What is your standard duration of antibiotic therapy? Educational events were recorded through April 2023.

Results
ID-AS experts provided AS education to 3742 PP dental providers, students/faculty over 20 months (Table 1). Prior to our lectures, most (90%) dentists were unfamiliar with dental AS; 88% prescribed clindamycin for penicillin allergies and 7 days were the most frequent duration for antibiotics.

Conclusion
PP dentists and faculty embraced AS education. Dental study clubs/CE forums provide excellent opportunities for ID-AS experts to engage and educate PP dentists. Dentists who attended AS lectures strongly support a 1-hour AS annual CE, similar to annual dental opioid CE required by many states.

Disclosures
All Authors: No reported disclosures
2201. Antibiotic-Prescribing Practices for Ambulatory Patients with Urinary Tract Infections in the Emergency Department
Authors: Khan Naveera , Norman Sarah J , Ramdeen Sheena 
Published: November 2023

Abstract

Background
Data on outpatient antibiotic stewardship for urinary tract infections (UTIs) are scarce. We describe the antibiotic-prescribing practices for ambulatory patients with UTI in the Emergency Department (ED) of a tertiary care center.

Methods
Consecutive sampling was used to identify non-hospitalized adult ED patients between January 1st 2022 and May 1st  2022, who had a urine culture or urinalysis and a diagnosis of UTI, dysuria, hematuria, urinary frequency, flank pain, or abdominal pain per ICD-10 codes. Patients with an indwelling urinary catheter within 48 hours of presentation or a diagnosis of a concurrent non-genitourinary tract infection were excluded. Of these, 115 were randomly selected. Excess antibiotic days were defined as the difference between the prescribed days and the maximum days recommended by the Infectious Diseases Society of America for a regimen.

Results
Women comprised 78.3% of the sample; mean age 45.1 +/- 19.5 years. There were no patients with a history of multidrug-resistant UTIs or ≥ 2 UTIs in the preceding 6 months. Uncomplicated cystitis (n=36) was treated with beta-lactams (55.6%), nitrofurantoin (41.7%) and trimethoprim-sulfamethoxazole (2.8%). Patients who received beta-lactams had a mean age of 56 +/- 23.6 years, with no documented rationale for using beta-lactams over other agents in any patient. The mean excess days of antibiotics for patients with uncomplicated cystitis was 0.94 days, most commonly with nitrofurantoin (mean excess days 1.8). There were 19 non-pregnant asymptomatic patients, 52.6% of these received antibiotics (median age 77.5 years) despite not meeting UTI diagnostic criteria. All patients with pyelonephritis were prescribed beta-lactams; mean duration 11.3 +/- 2.8 days. Of the 7 patients with negative urine cultures that resulted after ED discharge, none were contacted to stop antibiotics.

Conclusion
Antibiotic choice and duration, antibiotic prescription for non-pregnant asymptomatic patients, and lack of antibiotic de-escalation are potential areas to target antibiotic stewardship for UTIs in the ED for non-hospitalized patients.

Disclosures
All Authors: No reported disclosures
2221. Comparison of Vancomycin with Either Piperacillin/Tazobactam or Cefepime for the Incidence of Acute Kidney Injury in a Patient Population with a High Prevalence of Preexisting Kidney Dysfunction
Authors: Moran Ryan , Harris Jacklyn , Kolkmeyer Jessica 
Published: November 2023

Abstract

Background
Frequently used agents for empiric antibiotic therapy include vancomycin, cefepime, and piperacillin/tazobactam (PTZ). Documentation exists to suggest the combination of vancomycin and PTZ increases the risk of acute kidney injury (AKI) more than either alone. This interaction has not been specifically studied in a population with a high prevalence of preexisting kidney dysfunction. The purpose of this study is to investigate if the combination of vancomycin and PTZ increases the incidence of AKI compared to vancomycin with cefepime in this population.

Methods
This retrospective study compares hospitalized patients receiving vancomycin with either cefepime or PTZ. Inclusion criteria were age ≥ 18 and ≥ 72 hours concomitant receipt of vancomycin with either PTZ or cefepime. Exclusion criteria were AKI or dialysis prior to antibiotic initiation, receipt of both cefepime and PTZ, and being COVID-19 positive. Patients were assigned to one of the groups based on the antibiotics they received.
The two co-primary outcomes were the incidence of AKI in the entire study population and specifically in those with preexisting chronic kidney disease (CKD). Secondary outcomes include duration of hospitalization, duration of antibiotic therapy, mortality, severity of AKI, and incidence of dialysis initiation.

Results
Of 470 candidates screened, 276 were included in the trial with 164 and 112 in the cefepime and PTZ groups, respectively. Of these patients, 39% had CKD (185/470). Groups were evenly distributed concerning baseline characteristics except the cefepime group was significantly older by an average of 7.3 years (p &lt; 0.001). The primary outcome in the total study population occurred in 17.1% in the cefepime group and 39.3% in the PTZ group (p &lt; 0.001). In the CKD population, the PTZ group had a higher rate of AKI at 48.2% compared to 38% of cefepime (p = 0.389). There were no significant differences in any secondary outcomes.

Conclusion
These results suggest the combination of vancomycin and PTZ increases the risk of AKI. The study was unable to show a significant difference for those with preexisting CKD. It is unknown whether this is related to the presence of CKD or the small sample size. Additional research is needed to further evaluate vancomycin with PTZ in certain patient populations.

Disclosures
All Authors: No reported disclosures