bluuebunny/crossref_metadata_2025 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

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 < 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

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

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 >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

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 >1 mg/L and Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with aztreonam or ceftazidime MIC >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 < 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

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

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< 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

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

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

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 < 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 < 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
2237. Outcomes of Metronidazole Dosed Every 12 Hours Versus Every 8 Hours
Authors: Box Maggie , Duong Kelly , Molina Kyle
Published: November 2023

Background

Metronidazole (MTZ) is a mainstay treatment for anaerobic infections. Due to its pharmacokinetic and phamacodynamic properties, it can be dosed at 8 -, 12-, or 24-hour intervals. MTZ’s adverse effects depend on the cumulative dose, permitting less frequent administration. Less frequent dosing intervals may save nursing and pharmacy resources and improve patient compliance. Further, drug shortages of IV MTZ have prompted efforts to reduce utilization to preserve the availability of therapy. The objective of this study was to compare clinical outcomes of patients who received MTZ every 8 hours to every 12 hours.

Methods

This multicenter, retrospective study was conducted at Scripps Health from 1/1/2022 - 12/31/2022. Hospitalized adult patients who received MTZ, dosed at 500 mg every 8 hours or every 12 hours, for > 5 days for a pulmonary, intra-abdominal, or skin source were included. Patients were excluded if they received anaerobic antibiotics for > 72 hours prior to MTZ or concurrent to MTZ, or were pregnant, transitioned to hospice, or received MTZ for < 75% of the total therapy duration. The primary outcome was clinical cure and all-cause mortality within 30 days. Secondary outcomes were escalation of therapy, 30-day readmission, and duration of therapy.

Results

A total of 107 patients were included with similar baseline characteristics per group. The predominant infection source was intra-abdominal (55.1%), followed by skin (29.1%) and pneumonia (12.1%). An anaerobic organism was isolated in 16.8%, and source control was performed in 47.7%. All patients received concurrent antibiotics. Comparing every 8-hour (n = 52) versus every 12-hour (n = 55) MTZ, there was no difference in clinical cure (94.2% vs. 100.0%, p = 0.071) or all-cause mortality (1.9% vs. 0.0%, p = 0.301), respectively. For secondary outcomes, there was no difference in escalation of therapy (3.8% vs. 1.8%, p = 0.525) or 30-day readmission (28.8% vs. 25.5%, p = 0.693) between every 8 hours and every 12 hours. Total duration of antibiotics was similar between groups (14.2 vs 13.0 days, p = 0.541).

Conclusion

There was no difference in clinical cure, 30-day all-cause mortality, 30-day readmission, or escalation of therapy among patients receiving every 8 versus every 12-hour MTZ therapy.

Disclosures

All Authors: No reported disclosures
2249. Piperacillin-tazobactam-targeted provider education to improve utilization in a small community hospital
Authors: Gilmore Robert , Elgin Jennifer , Warren Cirle A
Published: November 2023

Background

Piperacillin-tazobactam is a broad-spectrum antibiotic commonly used for the treatment of Pseudomonas aeruginosa and other susceptible Gram negative and anaerobic infections. Piperacillin-tazobactam utilization is markedly elevated in our institution compared with regional and national rates.Thus, interventions to promote optimal use of this antibiotic to reduce utilization rates and negative consequences are needed.

Methods

Healthcare providers were provided with guidelines on piperacillin-tazobactam alternative treatments for various infections. Guideline handouts were disseminated and complemented by in-person presentations and one-on-one case discussions, as needed. Data on piperacillin-tazobactam utilization was gathered using BD Medmined’s medication analytics.

Results

Total antibiotic utilization at our institution is higher compared to national and regional rates. In the 2nd quarter (Q2) of 2021, piperacillin-tazobactam utilization was 44% and 26% above national and regional comparative rates, respectively. In Q2 2022, piperacillin-tazobactam was 59% and 45% higher, respectively. Immediately post-initiation of intervention (Q3 2022), utilization rates dropped to 34% and 22%, respectively and utilization dropped further in the succeeding quarters attaining comparable rates to national and regional comparator hospitals.

Conclusion

Providing healthcare providers with antibiotic-targeted education on alternative treatments can significantly reduce the utilization of piperacillin-tazobactam. Further studies are warranted to evaluate the long-term impact of this intervention on antibiotic stewardship in small community hospitals.

Disclosures

Cirle A. Warren, MD, Ser-109 Coactuate: Advisor/Consultant|Ser-109 Coactuate: Honoraria
2250. Fluoroquinolone Stewardship at a Veterans Affairs Facility: A Six Year Review
Authors: Glicksberg Jessica , Froehlich Morgan , Creed Mary , Psevdos George
Published: November 2023

Background

Increased utilization of antibiotics leads to decreased antimicrobial susceptibility, a well-established phenomenon. Antimicrobial stewardship programs (ASP) promote appropriate prescribing of antibiotics by decreasing inappropriate use, aiming to improve patient outcomes and reducing antimicrobial resistance. Fluroquinolones (FQ) are among the most prescribed antibiotics. We describe out institutional FQ use since inception of our ASP and followed the trend for susceptibility of Enterobacteriaceae and Pseudomonas

Methods

Northport Veterans Affairs Medical Center (VAMC) provides care for over 30000 Veterans in Long Island, New York, with emergency room, acute care hospital, nursing homes and outpatient clinics A Retrospective review investigated FQ use by total refills per year and by days of therapy per 1000 patient days at Northport VAMC from 2012 to 2022, along with review of local annual antibiograms focusing on ciprofloxacin susceptibility to E. coli, K. pneumoniae, P. mirabilis and P. aeruginosa. An ASP in our facility was initiated in 2016. FQs are restricted antibiotics and require approval by the infectious diseases team (attendings, fellows, pharmacist)

Results

Figure 1 provides the outpatient total fills per year for Ciprofloxacin, Levofloxacin, Moxifloxacin. Inpatient FQ use during the ASP years was low: Figure 2 shows the FQ inpatient use (days of therapy/1000days) from 2019 to 2022. Comparing years 2012-2016 vs 2017-2022 there was a decrease in fills of ciprofloxacin (median 604 vs. 308 fills, P: 0.009), levofloxacin (276 vs. 116, P: 0.032), and moxifloxacin (116 vs. 14, P: 0.015). By same period comparison (see figure 3), Ciprofloxacin susceptibility for E. coli ranged median 66.5% to 61.5%, P: 0.126, K. pneumoniae 67% vs. 75.5% P: 0.086, P. mirabilis 45% vs. 47.5% P: 0.451, and P. aeruginosa 63% vs. 68.5% P: 0.308

Figure 2

inpatient FQ use 2019 to 2022

Figure 3

Ciprofloxacin susceptibility trend over time

Conclusion

There was a statistically significant decrease in the use of FQ in the outpatient setting after ASP was initiated in our facility. Although there was a trend in improvement in ciprofloxacin susceptibilities for Klebsiella, Proteus, and Pseudomonas, it was not statistically significant. Nevertheless, our results show that reducing FQ consumption can prevent worsening susceptibility trends for enteric gram negatives and Pseudomonas.

Disclosures

All Authors: No reported disclosures
2257. Cost-Benefit Analysis of Fidaxomicin (FDX) as First Line Treatment for Initial Episode of Clostridioides difficile Infection (CDI) during the COVID-19 Pandemic: A Quality Control/Improvement (QC/QI) Project at a Tertiary Care Veterans Affairs Medical Center (VAMC) over a 4-year period
Authors: Khaja Sumaiya F , Kuhn Ryan , Ali Sajjad , Natesan Suganthini Krishnan
Published: November 2023

Background

In 2021, Clostridioides difficile infection treatment guidelines were updated to recommend fidaxomicin over oral vancomycin as first-line therapy for initial and recurrent episodes of CDI. The aim of this analysis is to evaluate the cost benefit advantage of using fidaxomicin as first line therapy for the first episode of CDI.

Methods

A retrospective review of outpatient oral vancomycin and fidaxomicin use at the VAMC in Detroit, Michigan was conducted by evaluating total prescription fills per 1000 unique patients from 2019 to 2022. This study was done during the COVID-19 pandemic when there was an increased use of antibiotics for respiratory infections, and after the updated IDSA guidelines recommending fidaxomicin as first line therapy for initial and first recurrence of CDI. Diagnosis of CDI was based on clinical presentation and a positive stool C diff PCR test. Despite substantial cost of FDX, the expectation was that there would be a significant reduction in recurrent CDI, hospitalizations, length of stay, all of which would offer a cost-benefit advantage.

Results

There was a 5-fold increase in the use of fidaxomicin in 2021-2022 compared to 2018-2019. Its use was directly proportional to the increased use of respiratory quinolones and Beta lactam antibiotics for respiratory infections during the COVID-19 pandemic in 2020. Insurance co-pays were high and the FDX company support programs failed to cover veterans with Medicaid/Medicare coverage. Veterans were unable to complete the 10-day course of FDX as it was unaffordable. They had to be transitioned to oral vancomycin to complete the 10-day course for CDI.

Conclusion

Reduction of recurrent CDI may not offset the higher up-front cost of fidaxomicin ($2,400/10 days), compared to oral vancomycin ($30/10 days). This QC/QI analysis over a 4-year period revealed that increased use of fidaxomicin as first-line treatment for CDI did not translate into a cost advantage through decreases in CDI recurrence, given the high cost of fidaxomicin. Reduction in cost of fidaxomicin to < $1,200 may be needed to achieve the expected cost benefit. Based on our data, starting November 2022, FDX has been restricted in our institution. Prescription for FDX requires ID approval, and is reserved for recurrent CDI and not for the first episode of CDI.

Disclosures

All Authors: No reported disclosures
2285. Using Genomic Sequencing to Describe SARS-CoV-2 Transmission Dynamics in U.S. Major League Soccer Clubs
Authors: Velasquez-Reyes Joseline , Carmola Ludy R , Turcinovic Jacquelyn , Schneider Isaac , Putukian Margot , Sherry Kyle , Akula Natalie , Rischmann Owen , Silvers-Granelli Holly , Connor Bradley A , Angelo Kristina , Kozarsky Phyllis E , Libman Michael , Huits Ralph , Hamer Davidson H , Bourque Daniel , Fairley Jessica K , Piantadosi Anne , Connor John
Published: November 2023

Background

In 2020–2022, U.S. Major League Soccer (MLS) used SARS-CoV-2 mitigation protocols that included masking, social distancing, avoiding contact with others outside of training and games, testing, quarantine, and isolation. In addition to isolation for those who tested positive, a SARS-CoV-2 genomic sequencing strategy was developed to identify whether infections were associated with intra-league transmission.

Methods

Nasopharyngeal swabs were collected by MLS club medical staff from players and staff from February 2021 through September 2022. During this time, surveillance testing changed from daily to weekly to testing only symptomatic players and staff.

SARS-CoV-2 positive samples were analyzed using amplicon-based whole genome sequencing. A phylogenetic tree was constructed using Nextstrain to visualize genomes from infected players and staff in the context of genomes available on GISAID circulating in the United States during corresponding time periods. To identify transmission links, all genomes were compared in a pairwise fashion. Genomes that were 0–2 nucleotides different were considered part of direct transmission clusters.

Results

Of 250 samples that were rtPCR positive for SARS-CoV-2, 215 (86%) were sequenced. Phylogenetic analysis showed a broad diversity of lineages, including some predominant overseas (e.g., AY.98.1). Pairwise comparison revealed SARS-CoV-2 sequences from 7 individuals appeared to be linked. These individuals were on 2 different MLS teams; there was an off-field exposure (dinner). Five (71%) had identical SARS-CoV-2 sequences; 2 had sequences that were 1 nucleotide different at the consensus level. Subconsensus genome analysis revealed that differences of 1 nucleotide were due to subconsensus mutations fluctuating below and above 50%, suggesting all 7 individuals were part of a transmission cluster. Phylogenetic analysis revealed that the sequences from the cluster were distinct from reference sequences and were likely a unique transmission chain.

Conclusion

SARS-CoV-2 transmission may occur within, and even between, professional sports teams. Pairwise comparison of individual genomes can provide improved granularity to identify clusters and understand SARS-CoV-2 transmission.

Disclosures

Davidson H. Hamer, MD, Kephera Diagnostics: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Trinity Biotech, LLC: Advisor/Consultant|Valneva: Advisor/Consultant|Valneva: Grant/Research Support Daniel Bourque, MD, Kephera Diagnostics: Grant/Research Support
2286. A comparison of SARS-CoV-2 wastewater-based surveillance in a sentinel community versus a large metropolitan sewershed in Massachusetts, 2020-2023
Authors: Brown Tyler , Rao Sowmya R , Begemann Daniel , Amaya Flor , Keppard Barry , Mohareb Amir , Bates Samantha , Alonso Cristina , Jia Katherine M , Levison Julie H , Ryan Edward T , LaRocque Regina C
Published: November 2023

Background

Many wastewater-based surveillance (WBS) programs for COVID-19 sample from distal endpoints of sewage treatment systems (for example, sewage treatment plants). SARS-CoV-2 RNA measurements from these endpoints represent highly aggregated cross-sections from entire sewage systems, and are inherently unable to capture local variation in COVID-19 disease activity. Importantly, using highly aggregated samples from sewage system endpoints may limit the utility of SARS-CoV-2 RNA measurements as a leading indicator for forecasting applications. Geographically-focused, hyperlocal sampling in communities with more intense and/or earlier COVID-19 epidemic activity is a promising strategy for enhancing the public health value of WBS.

Chelsea versus Boston-wide SARS-CoV-2 wastewater RNA concentration over time

Methods

We examined SARS-CoV-2 RNA data in Chelsea, Massachusetts, a Boston-area community that has experienced disproportionately high COVID-19 disease burden across all phases of the epidemic thus far. Between November 2020 and April 2023, we collected biweekly samples from four local sewershed locations in Chelsea, which were analyzed for SARS-CoV-2 RNA concentration by BioBot Analytics. We compared these local measurements to those for identically analyzed samples collected at a distal sewer system endpoint (Massachusetts Water Resource Authority Deer Island Treatment Plant), for the same time points over the same collection period.

Results

Local sewershed SARS-CoV-2 RNA concentrations in Chelsea were consistently higher across all three major epidemic phases (pre-Delta, Delta, and Omicron) analyzed in our dataset. During the onset of the Delta wave, SARS-CoV-2 RNA concentrations in Chelsea increased earlier than Boston-wide levels measured at the sewer system endpoint.

Conclusion

Local wastewater sampling can facilitate pre-emptive and tailored public health responses to more effectively counter the burden of SARS-CoV-2 in disproportionately affected communities. Sampling in these “sentinel” communities may improve the utility of SARS-CoV-2 wastewater RNA concentrations as a leading indicator for COVID-19 forecasting applications.

Disclosures

Julie H. Levison, MD, MPhil, MPH, eMED, LLC.: Advisor/Consultant
2295. Documented SARS-CoV-2 Transmission Events Between Patients and Hospital Staff
Authors: Han Alison , Bailin Heike , Kwan Jennifer , Bell Michael , Decker Brooke K , Palmore Tara
Published: November 2023

Background

Non-Pharmaceutical Interventions (NPIs) were critical for the protection of healthcare personnel (HCP) from SARS-CoV-2 infection throughout the pandemic. Our review of several instances of patient-to-HCP, HCP-to-patient, and HCP-to-HCP spread showed that transmission events were primarily associated with not wearing masks.

Methods

Risk of transmission was assessed from tracing interviews. Possible or probable workplace-acquired COVID-19 was assessed in cases with high-risk exposures to infectious patients or staff and prolonged contact and plausible exposure timeline. HCP with dual masking between case and contact (both wearing a tight-fitting medical mask) were considered at no or low risk for exposure. Whole genome sequencing information was available for suitable samples in a subset of case studies.

Results

From March 3, 2020-March 31, 2023, there were 3,513 SARS-CoV-2 infections among healthcare workers. Of the total known HCP infections, 249 cases were possibly or probably associated with the workplace. An additional 25 cases with suspected workplace transmission were found to have low-risk contacts at work, but competing high-risk exposures outside of work. Stratifying by transmission vector dynamic, 146 (58.6%) had a documented epidemiologic link to another HCP within the workplace. Five (2.0%) HCP cases had a documented epidemiologic link to a patient and 1 (0.4%) had a documented epidemiologic link to another HCP and a patient. In 2 instances HCP were epidemiologically linked to a subsequent patient infection. Whole viral genome sequencing of suitable samples refuted workplace transmission in some cases and substantiated the linkage from tracing data in others.

Conclusion

After accounting for reported exposure sources, workplace transmission rates were extremely low in instances where NPIs were applied. Suspected transmission events were associated with instances where masking was relaxed between co-workers or in patient care instances where masking was not feasible by the patient.

Disclosures

Tara Palmore, MD, Abbvie: Grant/Research Support|Gilead: Grant/Research Support|Rigel: Grant/Research Support
2297. Trends in Respiratory Pathogens Detected by Using a Multiplex PCR Panel during the Different COVID-19 Pandemic Phases in Taiwan
Authors: Hsu Yu-Lung , Low Yan-Yi , Hsiao Chiung-Tzu , Chang Yu-Chang , Shih Hong-Mo , Lin Hsiao-Chuan , Hwang Kao-Pin , Hsueh Po-Ren
Published: November 2023

Background

The COVID-19 pandemic has greatly affected other respiratory infectious diseases. Taiwan's government implemented strict control measures initially, followed by relaxing measures, which may have impacted the incidence and distribution of other respiratory pathogens. This study aims to investigate the epidemiology of respiratory pathogens in Taiwan during different COVID-19 pandemic phases.

Methods

This retrospective study enrolled patients who visited China Medical University Hospital and China Medical University Children's Hospital in Taiwan between January 2020 and December 2022 during the COVID-19 pandemic. The respiratory tract specimens of these patients were detected using a commercial multiplex PCR-based panel assay that could identify 19 respiratory viruses and 4 bacterial pathogens. The study analyzed and compared the distribution patterns of respiratory pathogens among patients across three phases of the COVID-19 pandemic in Taiwan. These phases were divided into the transmission-blocking phase (period 1: January 2020 - December 2020), the transitional phase (period 2: January 2021 - December 2021), and the coexistence phase (period 3: January 2022 - December 2022).

Results

A total of 5,820 patients were included in the study. Of which,1,780 (30.6%) were positive for at least one respiratory pathogen. The most commonly detected virus was human rhinovirus/enterovirus (939/2492, 37.7%), followed by RSV (406/2492,16.3%), parainfluenza 3 (402/2492,16.1%), and adenovirus (261/2492,10.5%). Co-detection of multiple respiratory pathogens was observed in 9.5% of patients. Human rhinovirus/enterovirus was mainly detected throughout the three periods, peaking in the summer and winter. Human metapneumovirus and adenovirus were predominant during period 2, peaking in the summer, while parainfluenza 3 and RSV were predominant during period 3, peaking in the winter.Figure 1.Monthly respiratory pathogen distribution during three years of COVID-19 pandemicFigure 2.Monthly distribution of sample and detection rate during three years of COVID-19 pandemic

Conclusion

This study showed significant changes in the detection rates of non-SARS-CoV-2 respiratory pathogens during different phases of the COVID-19 pandemic in Taiwan. These findings highlight the importance of continued surveillance of respiratory pathogens beyond COVID-19 to better understand their epidemiology and inform public health interventions.

Disclosures

All Authors: No reported disclosures
2318. Utility of Routine Asymptomatic Post-Admission SARS-CoV-2 Screening in a Rehabilitation Facility
Authors: Williams Victoria R , Robinson Larry , Eisenberg Morty , Kozak Robert , Virdi Kuldeep , Candon Heather , Leis Jerome A
Published: November 2023

Background

SARS-CoV-2 testing is recommended for symptomatic patients, and asymptomatic testing following known exposure or on admission during periods of high community incidence. The role of post-admission asymptomatic screening is less clear. We evaluated the impact of routine weekly asymptomatic testing in a 178 bed rehabilitation setting that was experiencing frequent COVID-19 outbreaks following the emergence of the Omicron variant.

Methods

At baseline (April 1, 2021 to March 31, 2022), all patients were tested for SARS-CoV-2 in 4 situations: 1) routinely on admission (≤5 days); 2) in response to the development of new symptoms consistent with COVID-19 infection; 3) following exposure to a patient with COVID-19; and 4) as part of unit wide prevalence testing during suspected or confirmed outbreak. Routine weekly unit wide asymptomatic prevalence screening was introduced April 1, 2022 to March 31, 2023. An uncontrolled before-after study was performed assessing yield of these testing strategies and the incidence of healthcare associated-COVID-19 (HA-COVID). A case was defined as a patient testing positive for SARS-CoV-2 who had not been previously infected with COVID-19 within the preceding 90 days. Patients deemed to be recovered positive based on prospective assessment were excluded.

Results

The intervention was associated with nearly double the number of SARS-CoV-2 tests (8857 vs. 4672), of which 8513 (96.1%) and 4582 (98.1%) were eligible for inclusion during intervention and baseline, respectively. The before-after comparison of testing positivity was similar for overall, admission, and suspect/confirmed outbreaks with yield of 1.4%/0.5%/3.2% versus 2.6%/1.8%/4.9%, respectively. The addition of routine weekly testing had extremely low yield of 0.2% (8/4022). The incidence of HA-COVID increased during the intervention period (3.4 vs. 1.1 per 1000 patient-days; p< 0.001).

Conclusion

In a rehabilitation setting, the addition of routine weekly asymptomatic prevalence testing of patients was of low yield when added to surveillance in place on admission, and for symptomatic or exposed patients. Despite the increased risk of HA-COVID associated with the emergence of the Omicron variant, these findings do not support routine weekly post-admission testing.

Disclosures

Jerome A. Leis, MD MSc FRCPC, Ontario Hospital Association, Ministry of Attorney General of Ontario, Seneca College: Expert Testimony