bluuebunny/crossref_metadata_2025_split huggingface dataset:
130. Antimicrobial Stewardship Practices in Community Pharmacies Across the United States
Authors: Lee Yuman , Bradley Nicole , Trinh Saralinh 
Published: January 2021

Abstract

Background
Antimicrobial stewardship (AMS) in the community is essential as majority of antibiotic prescribing occurs in the community. Pharmacists are recognized by the Center for Disease Control and Prevention (CDC) as co-leaders for leading implementation efforts to improve antibiotic use. The purpose of this study is to evaluate current AMS practices in community pharmacies across the United States (US) and identify challenges.

Methods
A 15-item survey was created based on CDC’s Core Elements of Outpatient AMS to assess current policies and practices in place, as well as collect baseline demographics and pharmacists’ perceptions. A survey invite was posted on the Facebook group, Pharmacist Moms, in September 2019. Participation was voluntarily and anonymous.

Results
Participants included 61 community pharmacists from 25 states across the US. 88.5% work in a chain pharmacy with 54.1% in staff positions and 37.7% in management. 37.7% have been practicing for &gt; 10 years, 36.1% for 6–10 years and 26.2% 5 or less years. Minimal responses met CDC’s Core Elements of AMS: commitment (27.9%), action (24.6%), tracking and reporting (14.8%), and education and expertise (23% for pharmacists, 9.8% for patients).
In regards to perception, 67.9% felt AMS is important in the community. 88.5% would participate in AMS if the opportunity were provided. 91.8% were unsure or had no plans to implement AMS within the next 2 years.
Common challenges include the lack of time/staff (83.6%), pushback from prescribers (68.9%), lack of leadership (57.4%), lack of financial incentives (52.5%), pushback from patients (52.5%), lack of pharmacist knowledge/training (39.3%), lack of funding/financial support (29.5%), lack of legal requirement (21.3%), lack of information technology support (19.7%), and lack of pharmacist interest (11.5%).
Current Trends of U.S. Community Pharmacies in Meeting CDC’s Core Elements of Outpatient Antimicrobial Stewardship

Challenges in Implementing Antimicrobial Stewardship in Community Pharamacies

Conclusion
Results from this study reveal the lack of AMS practices in community pharmacies. Pharmacists have a critical role in AMS, but many challenges exist in the community setting inhibiting the full potential of pharmacists in AMS efforts. This study highlights the importance and need for addressing these issues as regulations and strategies for AMS in community settings develop.

Disclosures
All Authors: No reported disclosures
1571. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against MDR Enterobacterales and Pseudomonas aeruginosa Collected in Latin America During the ATLAS Global Surveillance Program 2017-2018
Authors: Kazmierczak Krystyna , Lob Sibylle , Stone Greg , Sahm Daniel F 
Published: January 2021

Abstract

Background
Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C and some class D β-lactamases. Resistance caused by these β-lactamases often results in multidrug-resistance (MDR). This study evaluated the in vitro activity of CAZ-AVI and comparators against MDR Enterobacterales and Pseudomonas aeruginosa isolates collected from patients in Latin America.

Methods
Non-duplicate clinical isolates were collected in 2017-2018 in 10 countries in Latin America. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin (AMK), aztreonam (ATM), cefepime (FEP), colistin (CST), levofloxacin (LVX), meropenem (MEM), and piperacillin-tazobactam (TZP).

Results
The activity of CAZ-AVI and comparators against all isolates and MDR subsets is shown in the table. MDR rates for the studied species ranged from 17.6% among E. cloacae to 31.0% among K. pneumoniae. CAZ-AVI was active against 99% of Enterobacterales isolates and maintained activity against 85-99% of MDR isolates of the examined species. Only tigecycline showed comparable or higher activity. Among P. aeruginosa, CAZ-AVI was active against 86% of all isolates and 45% of MDR isolates; no other studied drug was more active. The three most common MDR phenotypes among Enterobacterales were 1) R to ATM, FEP, and LVX (n=538, 50% of all MDR Enterobacterales; 100% susceptible (S) to CAZ-AVI), 2) R to all sentinel drugs except AMK and CST (n=112, 10% of all MDR isolates; 88% S to CAZ-AVI), and 3) R to ATM, FEP, LVX, and TZP (n=111, 10% of all MDR Enterobacterales; 100% S to CAZ-AVI). The three most common MDR phenotypes among P. aeruginosa were 1) R to all sentinel drugs except CST (n=70, 22% of all MDR isolates; 20% S to CAZ-AVI), 2) R to AMK, LVX, and MEM (n=33, 10% of all MDR isolates; 33% S to CAZ-AVI), and 3) R to all sentinel drugs except AMK and CST (n=30, 9% of all MDR isolates; 70% S to CAZ-AVI).
Table

Conclusion
These in vitro data suggest that CAZ-AVI can be an effective treatment option for infections caused by MDR Enterobacterales and P. aeruginosa collected in Latin America.

Disclosures
Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1572. Combination Cefuroxime and Sulopenem is active in vitro against Mycobacterium abscessus
Authors: Dousa Khalid M , Nguyen David C , Kurz Sebastian G , Taracila Magdalena A , Bethel Christopher , Bonomo Robert A 
Published: January 2021

Abstract

Background
Mycobacterium abscessus (Mab) is a highly drug-resistant nontuberculous mycobacteria (NTM). Efforts to discover new treatments for Mab infections are accelerating with a focus on cell wall synthesis proteins (L, D-transpeptidases, LdtMab1-5, and D, D-carboxypeptidase) that are targeted by combination β-lactam antibiotics. The US Food and Drug Administration (FDA) has granted Qualified Infectious Disease Product (QIDP) to the oral and intravenous (IV) formulations of Sulopenem (SUL). Data on SUL in vitro activity against Mab is currently unavailable. Here, we evaluated activity of SUL alone and in combination with Cefuroxime salt (CEF) against representative clinical isolates belonging to the Mab complex. Both CEF and SUL are available in oral formulation and can be considered as oral step-down therapy.

Methods
Minimum inhibitory concentrations (MICs) of SUL and CEF alone and in combination were determined using microdilution. Approximately 5 x 105 colony-forming units (CFU) per milliliter were inoculated into Middlebrook 7H9 Broth supplemented with 10% (vol/vol) oleic albumin dextrose catalase and 0.05% (vol/vol) Tween 80. CEF was added at fixed concentration of 4 µg/ml to serial dilutions of SUL. Mab isolates were incubated with test agents at 30 °C for 48 h, and MIC was defined as lowest antibiotic concentration that prevented visible bacterial growth.

Results
Fifty-five clinically derived and previously characterized isolates were tested in these assays. MIC50 and MIC90 of CEF is 16 and 32 ug/ml; MIC50 and MIC90 of SUL is 2 and 4 ug/ml, the range of MICs are as follows: CEF (8 → 64 ug/ml); SUL (1→8 ug/ml); and SUL and CEF at fixed 4 ug/ml (&lt; 0.25 → 4 ug/ml). Combination SUL and CEF lowered MIC to &lt; 0.25 ug/ml in 52 clinical isolate (Figure).
Fig. MIC distributions of cefuroxime salt, sulopenem, sulopenem with 4 μg/ml cefuroxime monohydrate against 55 Mab clinical strains

Conclusion
Our results support the emerging hypothesis that dual β-lactam therapy is a promising strategy in the treatment of serious Mab infections. Investigating the biochemical rationale for this combination will support the application to clinical trials.

Disclosures
Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)
1576. Re-Evaluation of cefepime or piperacillin-tazobactam to Decrease Use of Carbapenems in ESBL-Producing Enterobacterales BloodStream Infections (REDUCE-BSI)
Authors: Vu Catherine H , Venugopalan Veena , Santevecchi Barbara A , Voils Stacy A , Cherabuddi Kartikeya , DeSear Kathryn 
Published: January 2021

Abstract

Background
The ideal therapy for treatment of bloodstream infections (BSI) due to ESBL-producing organisms is widely debated. Although prior studies have demonstrated efficacy of non-carbapenems (CBPNs) for ESBL infections, results from the MERINO study group found increased mortality associated with piperacillin/tazobactam (PT) when compared with meropenem for treatment of ESBL BSI. The goal of this study was to investigate patient outcomes associated with the use of CBPN-sparing therapies (PT and cefepime (CEF)) for ESBL BSI. The primary outcome was in-hospital mortality between non-CBPN (PT and CEF) and CBPN groups. Secondary outcomes included clinical cure, microbiologic cure, infection recurrence, and development of resistance.

Methods
This was a retrospective observational study of patients admitted to the hospital from May 2016 - May 2019 with a positive blood culture for an ESBL-producing organism. Patients receiving meropenem, ertapenem, PT, or CEF were included. Patients were excluded if &lt; 18 years old, receiving antibiotics for &lt; 24 hours, treated for a polymicrobial BSI, or receiving concomitant antibiotic therapy for another gram-negative (non-ESBL) infection.

Results
One hundred and fourteen patients were analyzed; 74 (65%) patients received CBPN therapy compared with 40 (35%) patients that received a non-CBPN (CEF N=30, PT N=10). There were no statistically significant differences in baseline characteristics between groups. The overall in-hospital mortality rate was 6% (N=7). Eight percent of patients (N=6) in the CBPN arm died compared to 3% (N=1) of patients in the non-CBPN arm, P = 0.42. No difference in mortality was detected between groups when evaluating subgroups with Pitt bacteremia score ≥4 (N=25), requiring ICU admission (N=50), non-genitourinary source (N=50), or by causative organism (N=76 E. coli; N=38 Klebsiella spp.). There was no difference between groups for secondary outcomes.

Conclusion
CEF and PT are reasonable options for the treatment of ESBL BSI and did not result in increased mortality or decreased clinical efficacy when compared to CBPNs in this cohort.

Disclosures
All Authors: No reported disclosures
1578. Treatments for complicated urinary tract infections (cUTI) caused by multidrug resistant (MDR) Gram-negative (GN) pathogens- a systematic review and network meta-analysis (NMA)
Authors: Reason Tim , Gill Karan , Longshaw Christopher , McCool Rachael , Wilson Katy , Lopes Sara 
Published: January 2021

Abstract

Background
Antimicrobial resistance is a major and growing threat to global public health. Cefiderocol (CFDC) is a new siderophore-cephalosporin with a wide activity spectrum covering all aerobic GN pathogens including all WHO critical priority pathogens, that was recently approved by FDA for the treatment of GN cUTI in susceptible organisms. We aim to understand the relative efficacy and safety of current treatment options for cUTI caused by MDR GN pathogens.

Methods
We conducted a systematic review to identify all relevant trials that investigated the efficacy and safety of antimicrobial regimens, for the treatment of GN pathogens in cUTI. Outcomes of interest included clinical cure and microbiological eradication (ME) at time of cure (TOC) and sustained follow up (SFU), and safety. Evidence networks were constructed using data for outcomes of interest and analyses were conducted in a frequentist framework using NMA methods outlined by the NICE decision support unit using the netmeta package in R.

Results
A total of 5 studies, 6 interventions and 2,349 randomised patients were included in the final analysis. Interventions included CFDC, imipenem-cilastatin (IPM-CIL), ceftazidime-avibactam (CAZ/AVI), doripenem (DOR), levofloxacin and ceftolozane-tazobactam (CEF/TAZ). Trials included predominantly Enterobacterales, and Pseudomonas aeruginosa and very few Acinetobacter baumannii. The patient population presented some clinical differences across trials, which were not adjusted for the NMA. Overall, there were numerical differences (especially in endpoints at SFU favouring CFDC), but all treatments showed similar efficacy and safety, with exception of higher ME rate at TOC for CFDC vs IPM, Table 1, also observed at SFU, consistent with the data from the individual clinical trial.
Table 1- Results for microbiological eradication
Table 1- Results for microbiological eradication

Conclusion
This NMA, showed superiority of CFDC vs IPM-CIL in ME at TOC and SFU and similar efficacy and safety vs all other comparators, with numeric differences favouring CFDC for outcomes at SFU. These traditional methodologies for NMA, are only valid within a similar pathogens pool and population across the trials, and may not reflect the full value of breadth of coverage that new therapeutic options bring for the treatment of MDR GN pathogens.

Disclosures
Tim Reason, PhD, Shionogi (Consultant) Karan Gill, MSc, Shionogi BV (Employee) Christopher Longshaw, PhD, Shionogi B.V. (Employee) Rachael McCool, PhD, York Health Economics Consortium (Employee, YHEC was commissioned by Shionogi to conduct the systematic review) Katy Wilson, PhD, York Health Economics Consortium (Employee, Shionogi commissioned YHEC to conduct the systematic review) Sara Lopes, PharmD, Shionogi BV (Employee)
1579. Burkholderia Returns: Are Two Drugs Better or Back to Bactrim?
Authors: Hedvat Jason , Kubin Christine J , Mehta Monica 
Published: January 2021

Abstract

Background
Trimethoprim-sulfamethoxazole (T/S) and levofloxacin are considered first line agents for the treatment of Burkholderia cepacia complex (Bcc). Combination therapy (CT) is frequently utilized despite limited clinical evidence supporting this. The objective of this study is to compare outcomes associated with different regimens for the treatment of Bcc infections.

Methods
This is a retrospective cohort study in non-cystic fibrosis adult patients with infection caused by Bcc from 2015 to 2019. The primary outcome is the composite of overall treatment failure defined as clinical failure, microbiologic failure, or mortality at 30 days. Secondary outcomes include mortality, clinical failure, microbiological failure, development of resistance, recurrence, and safety. Comparisons were performed using Chi-squared or Fischer’s exact test for categorical variables and Student’s t test or the Mann-Whitney U test for continuous variables, as appropriate. Multivariable logistic regression analysis was used to identify independent risk factors for overall treatment failure.

Results
Sixty-eight patients were included, 50 (74%) received monotherapy (MT) and 18 (26%) received CT. MT regimens included meropenem (n=19), ceftazidime (n=15), T/S (n=10), and other (n=6). Various combination regimens were utilized. MT recipients were significantly older, more likely to have renal disease, less likely to have an immunosuppression, and had a higher severity of illness. The most common site of infection was respiratory (78%). No difference was found for overall treatment failure between MT and CT (36.0% vs. 38.9%; p=0.947). No differences were found in the secondary outcomes (Table 1). Overall treatment failure did not differ by treatment regimens utilized. On multivariable analysis controlling for age, renal disease, CCI, immunosuppression, ICU admission, SOFA score, and receipt of MT, only SOFA score was associated with treatment failure [OR 1.43 (95% CI 1.15 to 1.77); p=0.001] and not MT [OR 1.22 (95% CI 0.25 to 5.97); p=0.808].
Table 1: Treatment Outcomes – MT versus CT

Conclusion
There were no differences in outcomes between MT and CT groups for the treatment of Bcc infection. Treatment outcomes appeared to be driven primarily by disease severity. Additional studies are needed to identify the optimal treatment regimens.

Disclosures
All Authors: No reported disclosures
1584. In Vitro Activity of Imipenem/Relebactam against Gram-Negative Pathogens from Patients with Bloodstream Infections in the United States and Canada – SMART 2018
Authors: Lob Sibylle , Hackel Meredith , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: January 2021

Abstract

Background
Relebactam (REL) inhibits class A and C β-lactamases, including KPC, and was approved in the United States combined with imipenem (IMI) and cilastatin for complicated urinary tract and intraabdominal infections. We evaluated the activity of IMI/REL against non-Morganellaceae (NME) and P. aeruginosa collected as part of the global SMART surveillance program from patients with bloodstream infections (BSI) in the US and Canada.

Methods
In 2018, 24 US and 8 Canadian hospitals each collected up to 50 consecutive aerobic or facultative gram-negative pathogens from patients with BSI. MICs were determined using CLSI broth microdilution and interpreted with 2020 CLSI breakpoints. Multidrug-resistance (MDR) was defined as resistance to ≥3 of the following sentinel drugs: amikacin, aztreonam, cefepime, ceftazidime (NME only), ciprofloxacin, colistin, imipenem, and piperacillin/tazobactam.

Results
The 5 most common species among 1463 collected BSI isolates were E. coli (46.9%), K. pneumoniae (16.0%), P. aeruginosa (8.5%), P. mirabilis (4.8%), and E. cloacae (4.3%). Susceptibility to IMI/REL and comparators of selected species and subsets of resistant phenotypes is shown in the table.
IMI/REL was active against 99.8% of NME isolates; only meropenem, ceftazidime/avibactam, and amikacin showed comparable activity. Per 2020 CLSI guidelines, Enterobacterales and P. aeruginosa isolates are no longer considered susceptible to colistin. IMI/REL maintained activity against 89-100% of NME isolates that were nonsusceptible (NS) to β-lactams or MDR. Among P. aeruginosa, IMI/REL was active against 94.4% of isolates; a susceptibility rate only exceeded by amikacin. The addition of relebactam lowered the MIC90 for P. aeruginosa from 16 µg/mL to 1 µg/mL. IMI/REL maintained activity against 40-77% of P. aeruginosa isolates NS to β-lactams or MDR; susceptibility rates only exceeded by amikacin.
Susceptibility to IMI/REL was similar in the US (99.8% of NME [n=846]; 93.8% of P. aeruginosa [n=96]) and Canada (99.7% of NME [n=339]; 96.4% of P. aeruginosa [n=28]).
Table

Conclusion
In the US and Canada, IMI/REL could provide an important treatment option for patients with BSI caused by resistant gram-negative organisms.

Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1585. Stenotrophomonas maltophilia Infections and Approaches to Treatment
Authors: Caffrey Aisling , Appaneal Haley J , Lopes Vrishali , LaPlante Kerry 
Published: January 2021

Abstract

Background
Current knowledge of the epidemiology of Stenotrophomonas maltophilia is limited to studies from several small international medical centers. Additionally, real-world approaches to treatment are not well described.

Methods
We included admissions to any Veterans Affairs (VA) medical center nationally, with positive S. maltophilia cultures collected from any culture site between January 2010 and April 2019. We reviewed epidemiologic factors of clinical characteristics and treatment. Treatment was assessed by mapping out all antibiotic exposures each day, and identifying differences (heterogeneity) in the antibiotics used and duration of their use.

Results
Over the study period, we identified 8,225 hospital admissions with positive S. maltophilia cultures. Patients were older (mean age 68.2 year) and male (97.6%), with 25.8% in the intensive care and 56.1% admitted from other healthcare settings. Respiratory cultures were most common (47.4%), followed by urine (21.4%), skin and soft tissue (17.4%), and blood (5.1%). Admissions were mostly 11 days long (median), with an inpatient mortality rate of 13.9%.
The median time to culture collection from admission was day 3 of the hospitalization, and the median time to culture completion was 4 days. Changes in therapy occurred before culture completion for 67.3% of admissions. Most admissions utilized different treatment approaches (antibiotic drug and duration treatment heterogeneity 89.7%), with a median of 4 changes in therapy. Fluroquinolones were utilized in 40.6% of admissions (initiated median 4 days from admission) and sulfamethoxazole/trimethoprim in 26.3% (initiated median 7 days from admission). Inpatient mortality was significantly higher among those with changes in therapy versus those without changes (15.0% vs 5.7%, p&lt; 0.0001), and among those without changes, mortality was significantly higher with monotherapy versus combination therapy (16.2% vs 2.6%, p&lt; 0.0001).

Conclusion
Among more than 8,000 admissions with positive S. maltophilia cultures in the VA nationally, identification of the organism and targeted therapy did not occur until 4-7 days from admission. Differences in clinical outcomes were observed among the different treatment approaches.

Disclosures
Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, PharmD, Shionogi, Inc. (Research Grant or Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)