bluuebunny/crossref_metadata_2025_split huggingface dataset:
1570. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales from ICU and Non-ICU Wards Collected in Latin America and Globally as part of the ATLAS Surveillance Program 2017-2018
Authors: Lob Sibylle , Kazmierczak Krystyna , 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 with activity against Enterobacterales producing class A, C and some class D β-lactamases. Resistance caused by these β-lactamases is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales isolates from patients in ICU and non-ICU wards.

Methods
Non-duplicate clinical isolates were collected in 2017-2018 from patients in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC &gt;1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC &gt;1 µg/ml.

Results
The activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global Enterobacterales were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI, which inhibited ≥97% of isolates from both ward types. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 66.5% and 68.1% of ICU and non-ICU isolates, respectively (of which 31.8% and 30.8%, respectively, carried metallo-β-lactamases [MBLs]). CAZ-AVI inhibited &gt;97% of MEM-NS MBL-negative isolates collected globally. Antimicrobial activity against all Enterobacterales from both ICU and non-ICU wards in Latin America (LA) was generally similar to the global average. Among MEM-NS isolates, antimicrobial activity of CAZ-AVI and TGC was higher in LA than the global average among isolates from both ward types, at least partly because of a lower proportion of MBL-positive isolates in this subset (15.8% and 17.9% in ICU and non-ICUs, respectively). CAZ-AVI inhibited 100% of MEM-NS MBL-negative isolates from LA.
Table

Conclusion
CAZ-AVI provides a valuable treatment option for infections caused by Enterobacterales that do not carry MBLs, including those among patients in ICU wards, where antimicrobial resistance is typically higher.

Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, 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)
1573. Daptomycin Resistant Enterococcus faecium: Combination Therapy Screening
Authors: Kebriaei Razieh , Stamper Kyle , Lev Katherine , Morrisette Taylor , Arias Cesar A , Rybak Michael J 
Published: January 2021

Abstract

Background
Enterococcus faecium infections are difficult to treat and there is a growing concern regarding the rising occurrence of daptomycin resistance. We have previously demonstrated that only daptomycin plus ampicillin combination was effective against DAP-R E. faecium R497. The efficacy and systematic screening DAP plus β-lactams and DAP plus other combinations against daptomycin-resistant strains of E. faecium has not been investigated. Here, we evaluated 40 selected single, dual and triple combinations of antibacterial regimens against two clinical isolates of DAP-R E. faecium (R497 and R496 (with daptomycin MIC of 16 and 32 µg/ml, respectively).

Methods
E.faecium R497 and R496 were tested against an array of antibacterial agents including daptomycin, tigecycline, linezolid, ertapenem, ceftaroline and ceftriaxone using MIC susceptibility tests and 24h time-kill curves (TKC). All susceptibility tests and TKCs were performed in MHB broth containing 50 mg/L calcium. TKCs were performed at half MIC or free peak concentration of each antibacterial (whichever was lower). Synergy was defined as &gt;2 log10 CFU/ml decrease compared to the most potent antibacterial agent.

Results
Susceptibility tests demonstrated resistance to all listed β-lactams for both organisms. TKCs demonstrated that combination of daptomycin-ertapenem, daptomycin-ceftriaxone and daptomycin-ceftaroline was not effective against R497. However, addition of ceftriaxone or linezolid to either daptomycin-ertapenem or daptomycin-ceftaroline combinations resulted in synergy against this organism. Combinations of daptomycin-ertapenem and daptomycin-ceftaroline were synergistic against R496. Addition of linezolid, ceftriaxone or tigecycline to either daptomycin-ceftaroline or daptomycin-ertapenem combination did not increase killing activity against R496.

Conclusion
Differential affinity of β-lactams to specific PBP isotypes seems to be a key parameter for the success of daptomycin- β-lactam combinations against multi-drug resistant E. faecium . The optimized use of double β-lactam therapy in addition to daptomycin can potentially lead to improved patient outcomes and preserving antibiotic therapy for serious enterococcus infections.

Disclosures
Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)
1577. Real-World, Multicenter Experience with Eravacycline for Various Infections
Authors: Alosaimy Sara , Lagnf Abdalhamid M , Molina Kyle , King Madeline , Pullinger Benjamin , Tart Serina , Jones Bruce M , Claeys Kimberly C , Truong James , Andrade Justin A , Biagi Mark , Pierce Michael , Cosimi Reese , Hobbs Athena L V , Perkins Nicholson , Huang Glen , Veve Michael , Morrisette Taylor , Davis Susan L , Davis Susan L , Rybak Michael J 
Published: January 2021

Abstract

Background
Eravacycline (ERV) is Food and Drug Administration approved in patients for the treatment of adults complicated intra-abdominal infections in 2018. Real-world data regarding the indications for ERV use are is limited. We evaluated the clinical/safety outcomes of patients treated with ERV in FDA and non-FDA approved indications.

Methods
Multicenter, retrospective, observational study from September 2018 to June 2020. Adult patients treated with ERV for ³ 72 hours were included. The primary outcome was 30-day survival. Secondary outcomes included a lack of 30-day infection-recurrence, resolution of signs/symptoms of infection and safety. All outcomes were measured from ERV start date.

Results
Overall, 108 patients were included from 12 geographically-distinct medical centers across the United States. The median(IQR) age was 60(52-67) years and 60% were male. Median(IQR) APACHE II and Charlson Comorbidity scores were 15(11-21) and 3 (2-6), respectively. The most common sources of infection were intra-abdominal (32%), and respiratory (24%). Common pathogens included Acinetobacter baumannii (19%), Klebsiella pneumoniae and Enterococcus faecium (16%). Infectious diseases consultation was obtained in 98%, and surgical interventions in 51% of cases. Patients often received active therapy prior to ERV(40%). Median(IQR) ERV therapy duration was 7.7(4.4-14.0) days. Among cases with documented cultures, ERV was initiated within a median(IQR) of 4.8(2.5-9.9) days. Combination therapy ³ 48 hours was given in 45%. The primary endpoint was achieved in 79%(85/108). Of patients who died(n=23), 57% were on monotherapy, 39% were critically ill, 39% had intra-abdominal as a source, and 30% had positive blood cultures. For secondary outcomes, 94%(102/108) lacked 30-day infection-recurrence and 74%(80/108) resolved signs/symptoms of infection. ERV was selected primarily for consolidation of the regimen(40%). Eight patients experienced a probable ERV-related adverse event, mainly gastrointestinal(87.5%) and none experienced clostridium difficile.

Conclusion
30-day survival was achieved in the majority of patients treated with ERV. Studies with longer follow-up are required to confirm these findings.

Disclosures
Madeline King, PharmD, Tetraphase (Speaker’s Bureau) Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)
131. Antimicrobial Usage for Respiratory Infections in Urgent Care Settings within the University of Washington Medicine Network
Authors: Huang Joanne , Escobar Zahra Kassamali , Jain Rupali , Chan Jeannie D , Lynch John B , D’Angeli Marisa A , Fang Victoria , May Larissa , Bryson-Cahn Chloe 
Published: January 2021

Abstract

Background
In an effort to combat antimicrobial resistance and adverse drug events, The Joint Commission mandated expansion of antimicrobial stewardship programs into ambulatory healthcare settings Jan 2020. The most common diagnoses resulting in inappropriate antimicrobial prescribing are respiratory infections. This study aimed to assess the rate of antibiotic prescribing for viral respiratory tract infections within six urgent care clinics affiliated with University of Washington Medicine health system in Seattle, WA.

Methods
This was a retrospective observational study from Jan 2019-Feb 2020. We used the MITIGATE toolkit; a resource that meets CDC’s core elements for outpatient stewardship. Patients were identified based upon pre-specified ICD-10 codes for viral respiratory infections. The primary outcome was the rate of unnecessary antimicrobial prescriptions for acute viral respiratory infections. Secondary outcomes evaluated inappropriate prescribing practices based on antibiotic selection, diagnosis, and age.

Results
Of 7,313 patients (6078 adults and 1235 pediatric) included, 23% were inappropriately prescribed antibiotics. The most common antibiotics inappropriately prescribed were azithromycin (62%), amoxicillin (13%), and doxycycline (13%). Fluoroquinolone (FQ) utilization was low (2%). Bronchitis (61%) and nonsuppurative otitis media (NSOM) (24%) were the most common viral diagnoses for which antibiotics were prescribed. Overall, unnecessary prescribing was lower in pediatrics than adults at 13% and 25%, respectively (p&lt; 0.001). Adults were more often prescribed antibiotics inappropriately for bronchitis and NSOM compared to pediatrics (p=0.0013).

Conclusion
Inappropriate prescribing practices across six urgent care clinics varied based upon age and diagnosis. Azithromycin is most often inappropriately prescribed but the low rate of FQ prescribing is encouraging. The lower rate of unnecessary prescribing in pediatrics is promising although there is room for improvement as 1 in 8 children were unnecessarily prescribed antibiotics. These findings support the need for antibiotic stewardship in the outpatient setting, targeting areas for azithromycin use and therapeutic management of bronchitis.

Disclosures
All Authors: No reported disclosures
1580. In Vitro Activity of Ceftazidime-Avibactam Against Enterobacterales and Pseudomonas aeruginosa Collected in Latin America as part of the ATLAS Global Surveillance Program, 2017-2019
Authors: Kazmierczak Krystyna , Valente Maria Lavinea , Lemos Elkin , Baudrit Monique , Quintana Alvaro , Irani Paurus , 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 with in vitro activity against Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa) carrying Class A, C and some Class D β-lactamases. We examined the in vitro activity of CAZ-AVI and comparators against isolates collected in Latin America (LA) as part of the ATLAS surveillance program.

Methods
Non-duplicate isolates of Ent (n=8416) and Psa (n=2521) were collected in 10 countries in Central America (CAC; Costa Rica, Dominican Republic, Guatemala, Panama [2018-2019 only]) and South America (SA; Argentina, Brazil, Chile, Colombia, Mexico, Venezuela [2017-2019]). Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2020 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with meropenem (MEM) MICs ≥2 µg/mL (Ent) or ≥4 µg/mL (Psa) were screened for β-lactamase genes.

Results
CAZ-AVI demonstrated potent in vitro activity against Ent collected in LA overall and in the CAC and SA subregions (95-99% susceptible (S)) that was comparable to or exceeded the activity of comparators including MEM, amikacin (AMK) and tigecycline (TGC) (Table). CAZ-AVI retained good activity against MEM non-susceptible (NS) Ent collected in SA (82% S; 6.9% of collected isolates) but activity was reduced against MEM-NS Ent from CAC (10% S; 5.7% of collected isolates), which included a high proportion of isolates carrying NDM-type metallo-β-lactamases (MBL). Among Psa, CAZ-AVI showed greater activity than the tested comparators against both all (86-92% S) and MEM-NS (61-66% S) isolates collected in LA overall and in the two subregions.
Table

Conclusion
CAZ-AVI showed potent in vitro activity against Ent and Psa collected from patients in the CAC and SA subregions of LA. Activity was also good against MEM-NS isolates from SA but was reduced against MEM-NS Ent from CAC that included a high proportion of MBL-positive isolates. The regional and country prevalence of different carbapenem-resistance mechanisms must be considered when evaluating treatment options; however, CAZ-AVI could provide a valuable therapeutic option for treatment of infections caused by Ent and Psa in LA.

Disclosures
Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Maria Lavinea Valente, MD, Pfizer Brazil (Employee) Elkin Lemos, MD, PhD, Pfizer Columbia (Employee) Monique Baudrit, MD, MSc, Pfizer Costa Rica (Employee) Alvaro Quintana, MD MSc, Pfizer, Inc. (Employee) Paurus Irani, MD, Pfizer United Kingdom (Employee) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1581. In Vitro Activity of Ceftolozane/Tazobactam against Pseudomonas aeruginosa from ICU and Non-ICU Patients with Respiratory Tract Infections in the Asia/Pacific region – SMART 2016-2018
Authors: Lob Sibylle , Kazmierczak Krystyna , Chen Wei-Ting , Khoo Yivonne , Balwani Kanchan , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: January 2021

Abstract

Background
Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Elevated antimicrobial resistance rates have been reported among pathogens collected in ICUs. Using isolates collected in Asia/Pacific as part of the global SMART surveillance program, we evaluated the activity of C/T and comparators against P. aeruginosa from patients with respiratory tract infections (RTI) in ICU and non-ICU wards.

Methods
In 2016-2018, 55 clinical laboratories in 11 Asia/Pacific countries collected 2530 P. aeruginosa isolates from RTI. MICs were determined using CLSI broth microdilution and interpreted with CLSI breakpoints. C/T-nonsusceptible isolates (except those from India) were screened by PCR and sequencing for genes encoding β-lactamases.

Results
Susceptibility to C/T in Asia/Pacific was 85.3% in ICUs and 92.2% in non-ICUs, 15-23 percentage points and 13-19 percentage points, respectively, higher than to meropenem, cefepime, and piperacillin-tazobactam. C/T maintained activity against 58.8% and 69.4% of meropenem-nonsusceptible isolates from ICU (n=294) and non-ICU patients (n=346), respectively. Acquired β-lactamases were detected in 64% of C/T-nonsusceptible isolates from ICUs (n=90; 54% MBL-positive, 1% GES carbapenemase-positive, 9% ESBL-positive) and in 47% of C/T-NS isolates from non-ICUs (n=86; 33% MBL-positive, 6% GES-carbapenemase-positive, 8% ESBL-positive). The table presents country-level rates of C/T-susceptible and carbapenemase-positive P. aeruginosa for countries with n &gt;20 in both ICU and non-ICU subsets.
Table

Conclusion
In Asia/Pacific overall, C/T maintained susceptibility rates &gt;85% in both ICU and non-ICU wards against P. aeruginosa isolates from RTI, with rates &gt;91% in most countries. Susceptibility was lower in countries with higher rates of carbapenemase-positive P. aeruginosa. C/T could provide an important treatment option for RTI infections caused by P. aeruginosa in the Asia/Pacific region.

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) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, 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)
1582. In Vitro Activity of Ceftolozane/Tazobactam against Enterobacterales and Pseudomonas aeruginosa Isolates from Geriatric Patients in the Asia/Pacific region – SMART 2016-2018
Authors: Lob Sibylle , Hackel Meredith , Chen Wei-Ting , Khoo Yivonne , Balwani Kanchan , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: January 2021

Abstract

Background
Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract and intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. We evaluated the activity of C/T against isolates collected from patients ≥65 years old as part of the SMART surveillance program in Asia/Pacific.

Methods
In 2016-2018, 49 clinical laboratories in Australia, Hong Kong, Malaysia, New Zealand, Philippines, Singapore, Korea, Taiwan, Thailand, and Vietnam each collected up to 250 consecutive gram-negative pathogens per year. Susceptibility was determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) Enterobacterales (ENT) and P. aeruginosa (PA) isolates were screened by PCR and sequenced for genes encoding β-lactamases (except ENT from 1 site in Taiwan).

Results
2082 PA (68.3% lower respiratory tract, 12.7% intraabdominal, 15.1% urinary tract, and 3.0% bloodstream infection isolates) and 8181 ENT isolates (29.8%, 27.8%, 32.5%, and 9.2%, respectively) were collected from patients ≥65 years old. In vitro susceptibility of PA and ENT stratified by length of hospital stay at time of specimen collection (LOS) is shown (Table).
C/T maintained activity against 75.5% of 518 P/T-NS, 67.9% of 395 cefepime-NS, and 71.6% of 377 meropenem-NS PA isolates. Among 136 C/T-NS PA isolates, 44.9% carried metallo-β-lactamases (MBL), 0.7% KPC, 1.5% GES carbapenemases, 5.9% only ESBL, and in 47.1% no acquired β-lactamases were detected. Among 878 characterized C/T-NS ENT, 14.1% carried MBL, 5.2% KPC, 3.3% OXA-48-like carbapenemases, and 53.5% AmpC and/or ESBL; no acquired β-lactamases were detected in 23.8% of isolates, of which 89.5% were species with intrinsic AmpC.
Table

Conclusion
Susceptibility of PA and ENT to all studied agents was lower for isolates collected ≥48 than &lt; 48 hours post-admission. C/T was active against &gt;92% of PA in both strata, 7-29 percentage points higher than the studied comparators except amikacin, and against &gt;84% of ENT, 4-30% higher than the comparators except meropenem and amikacin. C/T is a potential new treatment option for older patients with infections caused by ENT and PA in Asia/Pacific.

Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, 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)
1586. A Comparative Analysis of In Vitro Susceptibilities of Vancomycin-Resistant Enterococci Against Doxycycline, Minocycline, Tigecycline, Eravacycline and Omadacycline
Authors: Chua Mary Francine P , Nida Syeda Sara , Lawhorn Jerry , Sundareshan Vidya 
Published: January 2021

Abstract

Background
Vancomycin-resistant Enterococci (VRE) are nosocomial pathogens that cause significant morbidity and mortality especially among patients with chronic medical conditions, critical illness and prolonged hospitalizations. Majority of human infections are caused by two species— E. faecium and E. faecalis, and which can acquire resistance to ampicillin, aminoglycosides, and vancomycin. Our aim was to study the susceptibility profile of the VRE strains to the tetracycline group of antibiotics on isolates collected from our local hospital. Older tetracyclines and their novel derivatives are included in this study.

Methods
Eighty preserved isolates of VRE were tested against five tetracyclines, i.e. doxycycline, minocycline, tigecycline, eravacycline and omadacycline. Antimicrobial susceptibility testing was performed using the E-test method in accordance to CLSI guidelines. Isolates were then classified as either susceptible, intermediately susceptible or resistant based on established breakpoints.

Results
Eighty isolates (54 VRE. faecium and 26 VRE. faecalis) were included in the study. Out of 54 E. faecium isolates, 52 (96.3%) were susceptible to tigecycline, 15 (27.8%) were susceptible to minocycline, 14 (25.9%) were susceptible to doxycycline, 42 (77.8 %) were susceptible to omadacycline, and 52 (96.3%) were susceptible to eravacycline. Out of 26 E. faecalis isolates, 26 (100%) were susceptible to tigecycline, 2 (7.6%) were susceptible to minocycline, 2 (7.6%) were susceptible to doxycycline, 2 (7.6%) were susceptible to omadacycline, and 25 (96.15%) were susceptible to eravacycline.

Conclusion
Tigecycline and eravacycline exhibited better in vitro antimicrobial activity against vancomycin-resistant E. faecium and E. faecalis when compared to doxycycline and minocycline. Omadacycline showed a relatively favorable susceptibility profile for E. faecium, but less favorable for E. faecalis. Results of this study will be useful to incorporate in the local antibiogram and will guide antimicrobial stewardship efforts. These findings will not only add to existing knowledge on susceptibility profiles of the novel tetracyclines, i.e. eravacycline and omadacycline, but also on their applicability in the clinical setting.

Disclosures
All Authors: No reported disclosures