bluuebunny/crossref_metadata_2025_split huggingface dataset:
1588. Activity of Imipenem/Relebactam Against Clinical Isolates of P. aeruginosa and K. pneumoniae Collected in Asia/Pacific Countries – SMART 2016-2018
Authors: Lob Sibylle , Kazmierczak Krystyna , Chen Wei-Ting , Khan Tsz Kin , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: January 2021

Abstract

Background
Relebactam (REL) inhibits class A and C β-lactamases and was approved in the USA in combination with imipenem (IMI) and cilastatin for the treatment of complicated intraabdominal and urinary tract infections. We evaluated the activity of IMI/REL against clinical isolates collected in Asia/Pacific as part of the global SMART surveillance program.

Methods
In 2016-2018, 56 clinical laboratories each collected up to 250 consecutive, aerobic and facultative gram-negative pathogens from various infection sources per year. Susceptibility was determined using CLSI broth microdilution and CLSI breakpoints. IMI-nonsusceptible isolates (except from India) were screened for β-lactamase genes.

Results
Among 5501 K. pneumoniae and 4362 P. aeruginosa isolates, 46.6% and 65.3%, respectively, were collected from patients with lower respiratory tract infections, 25.6% and 17.1% from intraabdominal infections, 19.9% and 13.9% from urinary tract infections, and 7.2 and 2.9% from bloodstream infections. No infection source was specified for 0.7% of isolates from either species. 90.7% of collected K. pneumoniae isolates were IMI/REL-susceptible, ranging from 56.8% in India and ~80% in Thailand and Vietnam (~16% MBL-positive) to ≥97% in 7 countries (0-2% MBL-positive). 28.6% (202/707) of IMI-nonsusceptible K. pneumoniae were IMI/REL-susceptible. Of the 425 molecularly characterized IMI-nonsusceptible K. pneumoniae, 187 (44.0%) were MBL/OXA-48-like negative and 83.4% of these (156/187) were IMI/REL-susceptible; 82 isolates (19.3%) were KPC-positive and 91.5% of these (75/82) were IMI/REL-susceptible.
The table shows percent susceptible and percent MBL-positive among all collected P. aeruginosa isolates. 74.3% of IMI-nonsusceptible P. aeruginosa (n=1236) were IMI/REL-susceptible.
Table

Conclusion
IMI/REL was active against 91% of K. pneumoniae and 89% of P. aeruginosa isolates collected in Asia/Pacific overall, with higher activity in countries with lower MBL-positive rates. IMI/REL promises to be an important treatment option for IMI-nonsusceptible MBL-negative isolates, including KPC-producing K. pneumoniae.

Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Tsz Kin Khan, PhD, Merck, Sharp & Dohme, Hong Kong (Employee) 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)
1591. Antibiotic Utilization Trends in Veterans Affairs (VA) Patients with Carbapenem Resistant Enterobacteriaceae (CRE) Infections
Authors: Traversa Alfredo , Poggensee Linda , Wilson Geneva M , Suda Katie J , Evans Charlesnika T , Patel Ursula , Fitzpatrick Margaret A 
Published: January 2021

Abstract

Background
Carbapenem-resistant Enterobacteriaceae (CRE) are classified as an “urgent threat” to public health. Historically, colistin and tigecycline had been considered the drugs of choice for CRE infections, while other agents such as aminoglycosides and carbapenems had been used as adjunctive therapy. However, the FDA approval of ceftazidime-avibactam in 2015, meropenem-vaborbactam in 2017, and plazomicin in 2018 has expanded treatment options. Our purpose was to assess trends in CRE treatment for “new” antibiotics (ceftazidime-avibactam, meropenem-vaborbactam, plazomicin) as compared with other antibiotics with CRE activity.

Methods
This was a retrospective cohort study describing treatment of CRE blood stream infections (BSI) across 134 VA facilities from 2012-2018. Patients were censored at their first positive blood culture with CRE. Categorical data was assessed with a Fisher’s exact test or chi-square test. Trends test and logistic regression were used to describe changes in CRE treatment over time.

Results
724 patients with positive blood cultures for CRE were identified during the study period. Most patients were male (94%), white (32%) or Hispanic (38%), and the mean age was 71.5+11.9. Of those patients that received antibiotics (N=697), 53.4% carbapenems, 40.3% received aminoglycosides, 39.3% received polymyxins, 32.9% penicillins, 32.6% extended spectrum cephalosporins, 26.1% fluoroquinolones, 11.6% ceftazidime/avibactam, and 0.4% ceftolazone/tazobactam. Over the study period, there was decreased utilization of aminoglycosides (P &lt; 0.0026) and colistin (P&lt; 0.002) and increases in extended spectrum cephalosporins (P &lt; 0.001) and ceftazidime/avibactam (P &lt; 0.001).

Conclusion
Utilization of “older” agents such as aminoglycosides and polymyxins for the treatment of CRE blood stream infections is decreasing in the VA. Treating CRE with ceftazidime/avibactam, a newly approved antibiotic, and extended spectrum cephalosporins are increasing.

Disclosures
All Authors: No reported disclosures
1593. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against OXA-48 β-lactamase–Producing Enterobacterales Collected in International Medical Centers, Including the United States, in 2017–2018
Authors: Lin Lynn-Yao , Debabov Dmitri , Chang William 
Published: January 2021

Abstract

Background
OXA-48 is a carbapenemase with low-level hydrolytic activity toward cephalosporins. This study evaluated in vitro activities of ceftazidime-avibactam (CAZ-AVI), meropenem (MEM), meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T), and other antimicrobial agents against 113 OXA-48-producing Enterobacterales with multiple resistance mechanisms collected in a 2017–2018 global surveillance program.

Methods
Nonduplicate clinical isolates of 113 Enterobacterales were collected from medical centers in 25 countries in 2017–2018. In vitro susceptibility tests were performed by broth microdilution with a custom-made panel consisting of CAZ-AVI, ceftazidime (CAZ), MEM, MVB, C/T, colistin (COL), gentamicin (GEN), levofloxacin (LEV), and amikacin (AMK). Whole genome sequencing or quantitative PCR data were used to analyze resistance mechanisms, such as OXA-48, extended-spectrum β-lactamase (ESBL), original-spectrum β-lactamase (OSBL), and AmpC β-lactamase. Clinical and Laboratory Standards Institute breakpoints were applied for susceptibility interpretations.

Results
Of 113 OXA-48–producing clinical isolates, 20 carried OXA-48 alone. The remaining 93 isolates carried additional β-lactamases, including 63 with ESBL (CTX-M-15) + OSBL (SHV, TEM), 15 with AmpC (DHA, AAC, CMY) + ESBL (CTX-M-15), and 15 with OSBL (SHV, TEM). 99.1% (all but 1) of all isolates tested were susceptible to CAZ-AVI, whereas 71.7%, 17.7%, and 14.2% were susceptible to MVB, MEM, and C/T, respectively. Among isolates harboring multiple resistance mechanisms (OXA-48 + ESBL + OSBL; n=63), 98.4%, 69.8%, 11.1%, and 7.9% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively. Among isolates carrying OXA-48 + AmpC + ESBL + OSBL (n=15), 100%, 66.7%, 13.3%, and 13.3% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively (Table). Aminoglycosides (AMK and GEN) and other β-lactams (eg, CAZ) were 20%–90% active against these isolates. COL was the second most effective comparator, inhibiting 83.2% of these isolates.
Table

Conclusion
CAZ-AVI was the most effective agent in this study compared with other antibiotics, including β-lactams, β-lactam–β-lactamase inhibitor combinations, aminoglycosides, and COL, against OXA-48-producing Enterobacterales carrying multiple β-lactamases.

Disclosures
Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee)
1594. Antimicrobial Resistance Monitoring through the ATLAS Global Surveillance Program 2012-2018
Authors: Hackel Meredith , Sahm Daniel F , Dowzicky Michael 
Published: January 2021

Abstract

Background
Antimicrobial resistance is an increasingly serious threat to global public health. The Antimicrobial Testing Leadership and Surveillance (ATLAS) program has provided reliable, global, regional and local in vitro susceptibility data, including mechanisms of resistance, since 2004. In this analysis, data from the ATLAS program are used to measure the in vitro activity of several key gram-negative/gram-positive agents against major global pathogens.

Methods
A total of 251,837 gram-negative and 132,363 gram-positive non-duplicate, clinical isolates were collected from multiple infection sources from 743 unique sites in 74 countries during 2012-2018 in the ATLAS program. Identification was confirmed to the species level using MALDI-TOF spectrometry. Only one clinically relevant causative isolate per patient was accepted into the study. MICs were determined by broth microdilution following CLSI guidelines and interpreted using 2020 CLSI breakpoints. Phenotypic ESBL screening and confirmatory testing were performed using the CLSI M100 method.

Results
The in vitro activities of selected antimicrobial agents are provided in the table below. Based on percent susceptibility, ceftazidime-avibactam, amikacin, tigecycline, meropenem, and ceftolozane-tazobactam were the most active agents against most gram-negative isolates. The CRE rate among Enterobacterales isolates was 3.2%, with tigecycline and ceftazidime-avibactam the most active among this resistant subgroup. Ceftazidime-avibactam, ceftolozane-tazobactam, and amikacin were the most active agents against Pseudomonas aeruginosa. Ceftaroline, linezolid, tigecycline and vancomycin all showed good activity against gram-positive isolates.
Table

Conclusion
Ceftazidime-avibactam, ceftolozane-tazobactam, tigecycline, meropenem, and amikacin all showed good activity against a global collection of Enterobacterales. Ceftaroline, tigecycline, linezolid and vancomycin all exhibited excellent activity against gram-positive isolates. Continued monitoring of susceptibility patterns among common pathogens will provide useful information for determining treatment strategies.

Disclosures
Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor) Michael Dowzicky, MS, M.T. A.S.C.P., Pfizer, Inc. (Employee)
1596. Ceftolozane/tazobactam (Zerbaxa) for the Treatment of Pseudomonas aeruginosa (PSA) Bacteremia: A Systematic Literature Review (SLR)
Authors: Dillon Ryan J , Khankhel Zarmina S , De Anda Carisa , Bruno Christopher , Puzniak Laura A 
Published: January 2021

Abstract

Background
Bacteremia is a significant cause of morbidity and mortality. Several studies have shown this burden to increase among patients with multidrug resistant (MDR) PSA, and in those treated with inappropriate empiric therapy. Ceftolozane/tazobactam (C/T) is a combination of a novel antipseudomonal cephalosporin and an established β-lactamase inhibitor approved for the treatment of complicated urinary tract infection, complicated intra-abdominal infection and hospital-acquired and ventilator-associated bacterial pneumonia. In the absence of specific bacteremia clinical trial data; the aim of this study is to describe all published evidence relating to C/T for the treatment of Gram negative bacteremia.

Methods
This SLR includes all published evidence from December 2015 to March 2020 searched via the OVID platform: EMBASE, MEDLINE, and MEDLINE In-Process. In addition, data published (2018-2019) from the European Society of Clinical Microbiology and Infectious Diseases and Infectious Disease Week Congresses were included. Eligible publications were on adult patients treated with C/T reporting any clinical outcome where data were reported specifically for the bacteremia population.

Results
The SLR identified 1,455 citations, of which 24 publications representing 23 unique studies met eligibility criteria. This included primary and secondary bacteremia. Ten studies included patients with primary bacteremia, only 7 of which reported results specific to primary bacteremia patients. Despite heterogeneity in study design, patient and treatment characteristics, and a lack of detailed reporting; the majority of studies focused on MDR/ extensively drug resistant (XDR) infections (range: 68.3%-100%). Clinical success/ cure ranged from 33%-100%, with 6/7 studies at &gt;85%; 30-day mortality from 0%-67%, with 3/7 studies at 0% (Table 1).
Table 1. Clinical Outcomes reported among Primary Bacteremia population(s)

Conclusion
Although the number of C/T treated patients was small, favorable clinical outcomes were observed, even among highly resistant PSA infections. Heterogeneity was ubiquitous, with diverse and complex patient profiles identified. Further studies where outcomes are stratified by bacteremia status and by timing of C/T treatment are needed.

Disclosures
Ryan J. Dillon, MSc, Merck & Co., Inc., (Employee) Carisa De Anda, PharMD, Merck & Co Inc, (Employee) Christopher Bruno, MD, Merck & Co., Inc. (Employee) Laura A. Puzniak, PhD, Merck (Employee)
1599. Clinical Outcomes for Patients Treated with Fluoroquinolones for Bacteremia Caused by Enterobacteriaceae Reclassified as Not Susceptible by Updated CLSI Breakpoints
Authors: Fleischner Zachary , Szymczak Wendy , Weston Gregory 
Published: January 2021

Abstract

Background
Antibiotic resistance remains a pressing public health challenge. Antibiotic susceptibility testing is crucial to identify resistance and predict which antibiotics are most likely to be effective. In vitro minimum inhibitory concentrations (MICs) are interpreted using MIC breakpoints set for the United States by The Clinical and Laboratory Standards Institute (CLSI). In 2019 CLSI updated fluroquinolone (FQ) breakpoints for Enterobacteriaceae. Previously any isolate with an MIC ≤ 1 µg/mL of ciprofloxacin would be considered susceptible but based largely on pharmacokinetic/pharmacodynamic simulations the susceptibility breakpoint was revised to ≤ 0.25 µg/mL. However, the clinical relevance of this decision remains unclear.

Methods
All cases of Enterobacteriaceae bacteremia with isolates previously considered susceptible but reclassified as resistant (MIC = 1 µg/mL) in adults treated with FQs between 08/01/2018 and 07/31/2019 were identified. Demographics, clinical characteristics and outcomes were compared with an equal number of randomly selected isolates with an automated MIC reported as ≤ 0.5 µg/mL. Available stored isolates with a reported MIC of ≤ 0.5 µg/mL had manual E-testing performed to identify a more precise MIC.

Results
29 cases with an MIC = 1 μg/mL were compared with 29 controls with a MIC of ≤ 0.5. Only 3 cases and 1 control received FQs as empiric therapy, the remaining patients in each group were transitioned to FQ after a median of 4 days of other antibiotics. No significant difference was found for predetermined outcomes including 30 day mortality, escalation after starting FQ, length of hospital stay, and readmission in 30 days (see Table). No primary outcome was thought to be related to antibiotic failure. E-testing found no isolates with an MIC = 0.5 μg/mL.
Table 1

Conclusion
Patients with Enterobacteriaceae bacteremia treated with FQs for isolates reclassified as resistant had similar outcomes to those with lower MICs. While FQs are generally not recommended as first line empiric antibiotics, FQs may still be safe to use as stepdown therapy for isolates with a ciprofloxacin MIC = 1 μg/mL, particularly if the only alternative may be IV antibiotics. A larger study is needed to confirm this.

Disclosures
Gregory Weston, MD MSCR, Allergan (Grant/Research Support)
133. Creation of an Emergency Department (ED)-Specific Urine Antibiogram and Evaluation of Urinary Tract Infection (UTI) Prescribing Practices at a Tertiary Academic Medical Center
Authors: Broadbent Eleanor K , Caitlin Schanz , Boeser Kimberly D , Mason Jocelyn , Norton Laura E , Hirsch Elizabeth B 
Published: January 2021

Abstract

Background
Inpatient settings have been the focus of most antimicrobial stewardship (AS) practices; however, the Joint Commission has now published requirements for accredited ambulatory healthcare organizations to implement AS. This analysis aimed to create a urine isolate antibiogram and to evaluate microbiological data and prescribing practices for UTI patients in the ED.

Methods
This retrospective cohort study included adults admitted to either of two EDs at University of Minnesota Medical Center and diagnosed with a UTI between 1/1/2018 and 12/31/2018. Patients were excluded if subsequently admitted to an inpatient unit or if they had a repeat culture growing the same organism as the index isolate. Diagnosis of cystitis versus pyelonephritis was based on ICD-10 coding. Data including urinalysis and culture results, susceptibilities, empiric antibiotic selection, and readmissions were collected.

Results
Data from 350 isolates were collected for inclusion in the antibiogram. Patient characteristics corresponding to this isolate collection included 78.9% female, median age of 41 years, and 64.6% diagnosed with pyelonephritis. Escherichia coli was the most common organism (70%), followed by Klebsiella pneumoniae (5.4%) and Proteus mirabilis (4%). Combined susceptibilities of E. coli isolates from both EDs were: 49.4% ampicillin, 55.7% ampicillin/sulbactam, 69.8% sulfamethoxazole/trimethoprim, 83.7% ciprofloxacin (CIP), 85.7% cefazolin, 93.9% ceftriaxone, and 94.3% nitrofurantoin (NIT). The most common discharge antibiotics prescribed for cystitis patients were NIT (29.8%) and cephalexin (25%). Pyelonephritis patients were most frequently prescribed CIP (32.3%) and cefdinir (14.2%). Drug-bug mismatches occurred in 19.1% of patients (10.5% cystitis vs. 23.9% pyelonephritis). The rates of ED readmission within 96-hours and inpatient admission within 30 days, for any reason, were 4.3% and 9.1% respectively.

Conclusion
Based on the ED-specific urine antibiogram generated, NIT (cystitis) and CIP (pyelonephritis) could be considered first-line agents for empiric treatment of UTI at our institution. Drug-bug mismatches were more common in pyelonephritis patients. These data will be used to develop a treatment algorithm aimed at improving treatment of UTI in the ED.

Disclosures
Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)
1602. Comparative Activity of Ceftolozane-Tazobactam (C/T) and Ceftazidime-Avibactam (CZA) against Pseudomonas aeruginosa (PSA) from Patients with Cystic Fibrosis (CF)
Authors: Lasko Maxwell J , Nicolau David P , Kuti Joseph L 
Published: January 2021

Abstract

Background
Acute pulmonary exacerbations (APE) are a frequent cause of hospitalization for patients with CF. PSA is among the most common pathogen implicated in CF APE. Due to repetitive antibiotic courses, multidrug resistance (MDR) must be considered leaving few available intravenous antibiotic options. CZA and C/T are newer anti-PSA antibiotics that have been used to treat CF APE, but little data are available to compare their in vitro activity.

Methods
Non-duplicate, contemporary, clinical PSA (n=105) isolates were acquired from 85 patients during CF APE from 3 US hospital systems. MICs were assessed in at least triplicate by reference broth microdilution for C/T, CZA, aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), ciprofloxacin (CIP), levofloxacin (LVX), meropenem (MEM), piperacillin/tazobactam (TZP), and tobramycin (TOB). Current CLSI breakpoints were used to define susceptibility. Activity was further assessed in MDR, CAZ and MEM non-susceptible (NS) phenotypes.

Results
The mean patient age at isolate retrieval was 31 years (IQR: 21-43), and 20% were under 18 years. Mucoid morphology was observed in 48 (46%) isolates, and MDR defined in 41 (39%). Rates of susceptibility (MIC50/MIC90/%S) were: C/T (1/4/92%), CZA (2/8/90%), CAZ (4/64/68%), TZP (8/256/67%), TOB (2/32/63%), MEM (1/32/58%), ATM (8/64/57%), FEP (8/≥128/50%), CIP (2/8/27%), and LVX (4/16/24%). A mucoid phenotype did not alter %S (non-mucoid vs. mucoid) for C/T (93 vs. 92%) or CZA (91 vs. 88%). Among the 41 MDR PSA, activity was 2/16/83% and 4/16/76% for C/T and CZA, respectively. C/T, CZA, and MEM %S was 77, 69, and 23% for the 35 CAZ-NS isolates. C/T, CZA, and CAZ %S was 84, 77, and 39% for MEM-NS isolates.

Conclusion
These contemporary PSA from patients with CF displayed low susceptibility rates to most β-lactams, fluoroquinolones, and tobramycin, and MDR was common. C/T and CZA retained similarly high susceptibility against these isolates, including MDR strains and CAZ-NS/MEM-NS phenotypes. These data justify that both CT and CZA may be considered for CF APE due to PSA non-susceptible to current standard of care treatment options.

Disclosures
David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support) Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials))