FDA approval was extended in 2015 to treat patients with SSSI and CABP who developed bacteremia. Moreover, ceftaroline has also been used off-label to treat other infection types. We evaluated the S. aureus isolates were consecutively collected from 33 US medical centers in 2018-2020 and susceptibility tested by broth microdilution method against ceftaroline and comparators. Results were stratified by infection type and resistance profile. A total of 9,268 50/90, 0.25/1 mg/L) susceptibility (S) ranged from 98.5% (SSSI) to 95.4% . Ceftaroline retained potent activity and broad spectrum against methicillin-resistant S. aureus , with S rates varying from 96.3% (SSSI) to 89.2% . Overall S rate to erythromycin (ERY), levofloxacin (LEV), tetracycline (TET), and trimethoprim-sulfamethoxazole (TMP-SMX) were 44.0%, 67.9%, 94.1%, and 97.5%, respectively. Ceftaroline retained good activity against S. aureus resistant to ERY (94.8%S), LEV (91.4%S), TET (92.3%S), and/or TMP-SMX (98.7%S). Among the resistant subsets, ceftaroline S rates were generally highest among isolates from SSSI (93.1-100.0%), followed by other infections (81.8-100.0%), bloodstream infections , and pneumonia (86.6-98.1%); overall susceptibility was highest among TMP-SMX-R isolates (98.7%), followed by ERY-R (94.8%), MRSA (93.4%), TET-R (92.3%), and LEV-R (91.4%) isolates. Dalbavancin , teicoplanin , and vancomycin  exhibited complete activity (100.0%S), whereas daptomycin  and linezolid  were active against >99.9% of isolates.Ceftaroline  Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Qpex Biopharma (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, Affinity Biosensors  Involved: Self): Research Grant or Support; Allergan  Involved: Self): Research Grant or Support; Amicrobe, Inc  Involved: Self): Research Grant or Support; Amplyx Pharma  Involved: Self): Research Grant or Support; Artugen Therapeutics USA, Inc.  Involved: Self): Research Grant or Support; Astellas  Involved: Self): Research Grant or Support; Basilea  Involved: Self): Research Grant or Support; Beth Israel Deaconess Medical Center  Involved: Self): Research Grant or Support; BIDMC  Involved: Self): Research Grant or Support; bioMerieux Inc.  Involved: Self): Research Grant or Support; BioVersys Ag  Involved: Self): Research Grant or Support; Bugworks  Involved: Self): Research Grant or Support; Cidara  Involved: Self): Research Grant or Support; Cipla  Involved: Self): Research Grant or Support; Contrafect  Involved: Self): Research Grant or Support; Cormedix  Involved: Self): Research Grant or Support; Crestone, Inc.  Involved: Self): Research Grant or Support; Curza  Involved: Self): Research Grant or Support; CXC7  Involved: Self): Research Grant or Support; Entasis  Involved: Self): Research Grant or Support; Fedora Pharmaceutical  Involved: Self): Research Grant or Support; Fimbrion Therapeutics  Involved: Self): Research Grant or Support; Fox Chase  Involved: Self): Research Grant or Support; GlaxoSmithKline  Involved: Self): Research Grant or Support; Guardian Therapeutics  Involved: Self): Research Grant or Support; Hardy Diagnostics  Involved: Self): Research Grant or Support; IHMA  Involved: Self): Research Grant or Support; Janssen Research & Development  Involved: Self): Research Grant or Support; Johnson & Johnson  Involved: Self): Research Grant or Support; Kaleido Biosceinces  Involved: Self): Research Grant or Support; KBP Biosciences  Involved: Self): Research Grant or Support; Luminex  Involved: Self): Research Grant or Support; Matrivax  Involved: Self): Research Grant or Support; Mayo Clinic  Involved: Self): Research Grant or Support; Medpace  Involved: Self): Research Grant or Support; Meiji Seika Pharma Co., Ltd.  Involved: Self): Research Grant or Support; Melinta  Involved: Self): Research Grant or Support; Menarini  Involved: Self): Research Grant or Support; Merck  Involved: Self): Research Grant or Support; Meridian Bioscience Inc.  Involved: Self): Research Grant or Support; Micromyx  Involved: Self): Research Grant or Support; MicuRx  Involved: Self): Research Grant or Support; N8 Medical  Involved: Self): Research Grant or Support; Nabriva  Involved: Self): Research Grant or Support; National Institutes of Health  Involved: Self): Research Grant or Support; National University of Singapore  Involved: Self): Research Grant or Support; North Bristol NHS Trust  Involved: Self): Research Grant or Support; Novome Biotechnologies  Involved: Self): Research Grant or Support; Paratek  Involved: Self): Research Grant or Support; Pfizer  Involved: Self): Research Grant or Support; Prokaryotics Inc.  Involved: Self): Research Grant or Support; QPEX Biopharma  Involved: Self): Research Grant or Support; Rhode Island Hospital  Involved: Self): Research Grant or Support; RIHML  Involved: Self): Research Grant or Support; Roche  Involved: Self): Research Grant or Support; Roivant  Involved: Self): Research Grant or Support; Salvat  Involved: Self): Research Grant or Support; Scynexis  Involved: Self): Research Grant or Support; SeLux Diagnostics  Involved: Self): Research Grant or Support; Shionogi  Involved: Self): Research Grant or Support; Specific Diagnostics  Involved: Self): Research Grant or Support; Spero  Involved: Self): Research Grant or Support; SuperTrans Medical LT  Involved: Self): Research Grant or Support; T2 Biosystems  Involved: Self): Research Grant or Support; The University of Queensland  Involved: Self): Research Grant or Support; Thermo Fisher Scientific  Involved: Self): Research Grant or Support; Tufts Medical Center  Involved: Self): Research Grant or Support; Universite de Sherbrooke  Involved: Self): Research Grant or Support; University of Iowa  Involved: Self): Research Grant or Support; University of Iowa Hospitals and Clinics  Involved: Self): Research Grant or Support; University of Wisconsin  Involved: Self): Research Grant or Support; UNT System College of Pharmacy  Involved: Self): Research Grant or Support; URMC  Involved: Self): Research Grant or Support; UT Southwestern  Involved: Self): Research Grant or Support; VenatoRx  Involved: Self): Research Grant or Support; Viosera Therapeutics  Involved: Self): Research Grant or Support; Wayne State University  Involved: Self): Research Grant or Support Leonard R. Duncan, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services Shionogi (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)


Scientific Reportshttps://doi.org/10.1038/s41598-021-81759-7, published online 22 January 2021Correction to: In the original version of this Article, the Acknowledgements section was incomplete.“This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2019R1A6A1A1105566012).”now reads:“This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2019R1A6A1A1105566012). This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2020R1C1C1003289). This work was supported by the Technology Innovation Program  funded By the Ministry of Trade, Industry & Energy .”The original Article has been corrected.


Scientific Reports 10.1038/s41598-021-94887-x, published online 28 July 2021Correction to: The Acknowledgements section in the original version of this Article was incomplete.“Yolanda Hartman, Sheila Bright, Catherine Langford, Sharon Samuel, Erika McMillian, Brian Wright, Lauren Radford, Charlotte Jeffers, Jennifer Bartels, Tolulope Aweda, Jonathan McConathy, Jinda Fan, Norio Yasui, Dattatray Devalankar, Himani Modi, Morgan Richardson, and staff of the University of Alabama Cyclotron Facility are gratefully acknowledged for their contributions and informative discussions. Funding was provided by the National Institutes of Health/National Institute of Neurological Disorders and Stroke T32 UAB Training Program in Brain Tumor Biology (T32 NS048039), the UAB Brain Tumor Core Facility (USPHS NCI P20CA151129), the National Center for Advancing Translational Research of the National Institutes of Health (UL1TR001417), the American Cancer Society (RSG-18-006-01-CCE), National Cancer Institute (R01CA24058) and the Comprehensive Cancer Center at UAB (NIH P30CA013148). JWL is supported by funding from the Department of Defense (W81XWH-18-1-0315) and National Institutes of Health (R01AI148711). JMW is supported by the Department of Defense (RCRP CA170769). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”now reads:“Yolanda Hartman, Sheila Bright, Catherine Langford, Sharon Samuel, Erika McMillian, Brian Wright, Lauren Radford, Charlotte Jeffers, Jennifer Bartels, Tolulope Aweda, Jonathan McConathy, Jinda Fan, Norio Yasui, Dattatray Devalankar, Himani Modi, Morgan Richardson, and staff of the University of Alabama Cyclotron Facility are gratefully acknowledged for their contributions and informative discussions. Funding was provided by the National Institutes of Health/National Institute of Neurological Disorders and Stroke T32 UAB Training Program in Brain Tumor Biology (T32 NS048039), the UAB Brain Tumor Core Facility (USPHS NCI P20CA151129), the National Center for Advancing Translational Research of the National Institutes of Health (UL1TR001417), the American Cancer Society (RSG-18-006-01-CCE), National Cancer Institute (R01CA24058). This was supported by the Preclinical Imaging Facility at the O’Neal Comprehensive Cancer Center at UAB (NIH P30CA013148). JWL is supported by funding from the Department of Defense (W81XWH-18-1-0315) and National Institutes of Health (R01AI148711). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”The original Article has been corrected.


E. cloacae species complex (ECL), S. marcescens (SM), C. freundii species complex (CF), and P. aeruginosa (PSA) are common pathogens in a variety of clinical infections. These organisms can overexpress the chromosomal AmpC that encodes resistance to several β-lactams. We evaluated the activity of ceftazidime-avibactam (CAZ-AVI) and comparators against these organisms.Enterobacterales [ENT] and ≥16 mg/L for PSA) and considered probable AmpC hyperproducers. Isolates were susceptibility tested by broth microdilution method. 17,650 isolates, including 4,400 ECL, 2,074 SM, 1,644 CF, and 9,532 PSA, were consecutively collected from 88 US medical centers in 2016-2020. Among these isolates, 3,127 were ceftazidime-nonsusceptible  and CAZ-AVI was more active than MEM  against these organisms. C-T  and PIP-TAZ  exhibited limited activity against CAZ-NS ENT. Among comparator agents, only amikacin (99.0%S), tigecycline (95.6%S), and imipenem (92.1%S) showed good activity against CAZ-NS ENT. Also, CAZ-AVI retained activity against 86.7% of ENT isolates that were NS to CAZ and MEM (n=113). CAZ-AVI  and C-T  were the most active compounds tested against PSA and both retained activity against CAZ-NS PSA. CAZ-AVI  and C-T  activity against CAZ-NS PSA was comparable to tobramycin . Susceptibility to CAZ ranged from 73.6% (ECL) to 97.5% . Overall, 99.8% of ENT (99.7-99.9%) and 97.1% of PSA were CAZ-AVI-S; whereas 84.3% (79.0-97.7%) of ENT and 97.4% of PSA were ceftolozane-tazobactam (C-T)-S, 83.0% (78.5-94.8%) of ENT and 80.0% of PSA were piperacillin-tazobactam (PIP-TAZ)-S, and 98.4% (98.3-98.7%) of ENT and 79.5% of PSA were meropenem (MEM)-S. CAZ-AVI retained potent activity and broad spectrum against CAZ-NS ENT  (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Qpex Biopharma (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, Affinity Biosensors  Involved: Self): Research Grant or Support; Allergan  Involved: Self): Research Grant or Support; Amicrobe, Inc  Involved: Self): Research Grant or Support; Amplyx Pharma  Involved: Self): Research Grant or Support; Artugen Therapeutics USA, Inc.  Involved: Self): Research Grant or Support; Astellas  Involved: Self): Research Grant or Support; Basilea  Involved: Self): Research Grant or Support; Beth Israel Deaconess Medical Center  Involved: Self): Research Grant or Support; BIDMC  Involved: Self): Research Grant or Support; bioMerieux Inc.  Involved: Self): Research Grant or Support; BioVersys Ag  Involved: Self): Research Grant or Support; Bugworks  Involved: Self): Research Grant or Support; Cidara  Involved: Self): Research Grant or Support; Cipla  Involved: Self): Research Grant or Support; Contrafect  Involved: Self): Research Grant or Support; Cormedix  Involved: Self): Research Grant or Support; Crestone, Inc.  Involved: Self): Research Grant or Support; Curza  Involved: Self): Research Grant or Support; CXC7  Involved: Self): Research Grant or Support; Entasis  Involved: Self): Research Grant or Support; Fedora Pharmaceutical  Involved: Self): Research Grant or Support; Fimbrion Therapeutics  Involved: Self): Research Grant or Support; Fox Chase  Involved: Self): Research Grant or Support; GlaxoSmithKline  Involved: Self): Research Grant or Support; Guardian Therapeutics  Involved: Self): Research Grant or Support; Hardy Diagnostics  Involved: Self): Research Grant or Support; IHMA  Involved: Self): Research Grant or Support; Janssen Research & Development  Involved: Self): Research Grant or Support; Johnson & Johnson  Involved: Self): Research Grant or Support; Kaleido Biosceinces  Involved: Self): Research Grant or Support; KBP Biosciences  Involved: Self): Research Grant or Support; Luminex  Involved: Self): Research Grant or Support; Matrivax  Involved: Self): Research Grant or Support; Mayo Clinic  Involved: Self): Research Grant or Support; Medpace  Involved: Self): Research Grant or Support; Meiji Seika Pharma Co., Ltd.  Involved: Self): Research Grant or Support; Melinta  Involved: Self): Research Grant or Support; Menarini  Involved: Self): Research Grant or Support; Merck  Involved: Self): Research Grant or Support; Meridian Bioscience Inc.  Involved: Self): Research Grant or Support; Micromyx  Involved: Self): Research Grant or Support; MicuRx  Involved: Self): Research Grant or Support; N8 Medical  Involved: Self): Research Grant or Support; Nabriva  Involved: Self): Research Grant or Support; National Institutes of Health  Involved: Self): Research Grant or Support; National University of Singapore  Involved: Self): Research Grant or Support; North Bristol NHS Trust  Involved: Self): Research Grant or Support; Novome Biotechnologies  Involved: Self): Research Grant or Support; Paratek  Involved: Self): Research Grant or Support; Pfizer  Involved: Self): Research Grant or Support; Prokaryotics Inc.  Involved: Self): Research Grant or Support; QPEX Biopharma  Involved: Self): Research Grant or Support; Rhode Island Hospital  Involved: Self): Research Grant or Support; RIHML  Involved: Self): Research Grant or Support; Roche  Involved: Self): Research Grant or Support; Roivant  Involved: Self): Research Grant or Support; Salvat  Involved: Self): Research Grant or Support; Scynexis  Involved: Self): Research Grant or Support; SeLux Diagnostics  Involved: Self): Research Grant or Support; Shionogi  Involved: Self): Research Grant or Support; Specific Diagnostics  Involved: Self): Research Grant or Support; Spero  Involved: Self): Research Grant or Support; SuperTrans Medical LT  Involved: Self): Research Grant or Support; T2 Biosystems  Involved: Self): Research Grant or Support; The University of Queensland  Involved: Self): Research Grant or Support; Thermo Fisher Scientific  Involved: Self): Research Grant or Support; Tufts Medical Center  Involved: Self): Research Grant or Support; Universite de Sherbrooke  Involved: Self): Research Grant or Support; University of Iowa  Involved: Self): Research Grant or Support; University of Iowa Hospitals and Clinics  Involved: Self): Research Grant or Support; University of Wisconsin  Involved: Self): Research Grant or Support; UNT System College of Pharmacy  Involved: Self): Research Grant or Support; URMC  Involved: Self): Research Grant or Support; UT Southwestern  Involved: Self): Research Grant or Support; VenatoRx  Involved: Self): Research Grant or Support; Viosera Therapeutics  Involved: Self): Research Grant or Support; Wayne State University  Involved: Self): Research Grant or Support


S. aureus has been well established. We evaluated the in vitro activity of lefamulin against S. aureus from patients with cystic fibrosis (CF). Lefamulin is a first-in-class, oral and IV pleuromutilin antibiotic approved in the US, EU, and Canada for the treatment of community-acquired bacterial pneumonia (CABP) in adults. Lefamulin inhibits bacterial protein synthesis via a unique mechanism of action and its potency against n=224) were collected from the lower respiratory tract (LRT) of children (≤17 years old) with CF and LRT infection. Organisms were from qualified respiratory specimens and determined to be the probable cause of infection by the participant center. The isolates were collected in 2018-2020 from 22 medical centers in 11 countries and tested by broth microdilution methods at JMI Laboratories. Most isolates were from the US (43.3%), Spain (24.1%), France (20.5%), and Costa Rica (7.1%). Unique isolates , with 99.6% of isolates inhibited at ≤0.25 mg/L, consistent with the susceptible [S] breakpoint published by the US FDA, CLSI, and EUCAST. Only 1 lefamulin-non-S  isolate was observed, a methicillin-susceptible (MSSA) collected in Costa Rica in 2018 and carrying a vga(A) gene. Lefamulin retained potent activity against methicillin-resistant (R) S. aureus , azithromycin-R , levofloxacin-R , clindamycin-R , and gentamicin-R  isolates as well as those isolates with multiple resistance phenotypes. Against MRSA, susceptibility to azithromycin was 23.5% and to levofloxacin 64.7%. All isolates were susceptible to vancomycin, linezolid and ceftaroline (Table). Among isolates from the US (n=97), the MRSA rate was 30.9% and all isolates were Lefamulin-S .Lefamulin was highly active against the CF in vitro antibacterial activity against S. aureus from children with CF, regardless of resistance phenotype. Lefamulin may represent a valuable treatment option for CF patients with S. aureus LRT infections. Lefamulin demonstrated potent Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Susanne Paukner, PhD, Nabriva Therapeutics GmbH (Employee) Steven P. Gelone, PharmD, Nabriva Therapeutics US, Inc. (Employee) S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)


E. coli causing UTI in U.S. patients and evaluated the in vitro activity of GEP and comparators against various drug resistance (R) subsets.Gepotidacin (GEP) is a novel bacterial type II topoisomerase inhibitor in Phase 3 clinical trials for the treatment of gonorrhea and uncomplicated urinary tract infections (UTI). This study characterized fluoroquinolone (FQ)-not susceptible (not S) E. coli collected from 38 U.S. sites were included as part of the GEP Global UTI Surveillance Program (2019). Isolates were tested for susceptibility by broth microdilution. E. coli with MICs ≥0.5 mg/L for ciprofloxacin (not S) and/or ≥1 mg/L for levofloxacin (not S) were selected for screening of FQ-R mechanisms, and subjected to genome sequencing, followed by screening of FQ-R genes and QRDR mutations in GyrA, GyrB, ParC and ParE.1,035 E. coli met the screening criteria for FQ-not S (Table). Overall, GEP had MIC90 values of 2 mg/L and 4 mg/L against FQ-S and FQ-not S isolates, respectively. Nitrofurantoin had activity against the FQ-S and FQ-not S subsets , whereas amoxicillin-clavulanate (86.5% and 59.6%S) and trimethoprim-sulfamethoxazole (75.8% and 37.0%S) had limited activity. Most FQ-not S isolates  had double mutations in GyrA and ParC, followed by those isolates  with double mutations in GyrA and single mutations in ParC and ParE. The third most common genotype was represented by isolates  with double mutations in GyrA and a single mutation in ParC. GEP had MIC50 values of 1 mg/L or 2 mg/L and MIC90 values of 2 mg/L or 4 mg/L when tested against isolates with various combinations of QRDR mutations. 4.3% (12/277) of FQ-not S E. coli carried qnrB (6) or qnrS (6), and GEP  had MICs of 0.5–32 mg/L against this subset.A total of 26.8%  E. coli causing UTI in the U.S. In addition, GEP MIC did not seem to be affected by any combinations of FQ-R genes and QRDR mutations tested, except against the rare presence of qnrB/S genes. These data support the clinical development of GEP as a treatment option for UTI caused by FQ-S and FQ-not S E. coli isolates.GEP demonstrated potent activity against FQ-S and FQ-not S TableRodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Timothy B. Doyle, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Deborah Butler, n/a, GlaxoSmithKline, LLC (Employee) Nicole Scangarella-Oman, MS, GlaxoSmithKline, LLC (Employee) Jennifer M. Streit, BS, GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Qpex Biopharma (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, Affinity Biosensors  Involved: Self): Research Grant or Support; Allergan  Involved: Self): Research Grant or Support; Amicrobe, Inc  Involved: Self): Research Grant or Support; Amplyx Pharma  Involved: Self): Research Grant or Support; Artugen Therapeutics USA, Inc.  Involved: Self): Research Grant or Support; Astellas  Involved: Self): Research Grant or Support; Basilea  Involved: Self): Research Grant or Support; Beth Israel Deaconess Medical Center  Involved: Self): Research Grant or Support; BIDMC  Involved: Self): Research Grant or Support; bioMerieux Inc.  Involved: Self): Research Grant or Support; BioVersys Ag  Involved: Self): Research Grant or Support; Bugworks  Involved: Self): Research Grant or Support; Cidara  Involved: Self): Research Grant or Support; Cipla  Involved: Self): Research Grant or Support; Contrafect  Involved: Self): Research Grant or Support; Cormedix  Involved: Self): Research Grant or Support; Crestone, Inc.  Involved: Self): Research Grant or Support; Curza  Involved: Self): Research Grant or Support; CXC7  Involved: Self): Research Grant or Support; Entasis  Involved: Self): Research Grant or Support; Fedora Pharmaceutical  Involved: Self): Research Grant or Support; Fimbrion Therapeutics  Involved: Self): Research Grant or Support; Fox Chase  Involved: Self): Research Grant or Support; GlaxoSmithKline  Involved: Self): Research Grant or Support; Guardian Therapeutics  Involved: Self): Research Grant or Support; Hardy Diagnostics  Involved: Self): Research Grant or Support; IHMA  Involved: Self): Research Grant or Support; Janssen Research & Development  Involved: Self): Research Grant or Support; Johnson & Johnson  Involved: Self): Research Grant or Support; Kaleido Biosceinces  Involved: Self): Research Grant or Support; KBP Biosciences  Involved: Self): Research Grant or Support; Luminex  Involved: Self): Research Grant or Support; Matrivax  Involved: Self): Research Grant or Support; Mayo Clinic  Involved: Self): Research Grant or Support; Medpace  Involved: Self): Research Grant or Support; Meiji Seika Pharma Co., Ltd.  Involved: Self): Research Grant or Support; Melinta  Involved: Self): Research Grant or Support; Menarini  Involved: Self): Research Grant or Support; Merck  Involved: Self): Research Grant or Support; Meridian Bioscience Inc.  Involved: Self): Research Grant or Support; Micromyx  Involved: Self): Research Grant or Support; MicuRx  Involved: Self): Research Grant or Support; N8 Medical  Involved: Self): Research Grant or Support; Nabriva  Involved: Self): Research Grant or Support; National Institutes of Health  Involved: Self): Research Grant or Support; National University of Singapore  Involved: Self): Research Grant or Support; North Bristol NHS Trust  Involved: Self): Research Grant or Support; Novome Biotechnologies  Involved: Self): Research Grant or Support; Paratek  Involved: Self): Research Grant or Support; Pfizer  Involved: Self): Research Grant or Support; Prokaryotics Inc.  Involved: Self): Research Grant or Support; QPEX Biopharma  Involved: Self): Research Grant or Support; Rhode Island Hospital  Involved: Self): Research Grant or Support; RIHML  Involved: Self): Research Grant or Support; Roche  Involved: Self): Research Grant or Support; Roivant  Involved: Self): Research Grant or Support; Salvat  Involved: Self): Research Grant or Support; Scynexis  Involved: Self): Research Grant or Support; SeLux Diagnostics  Involved: Self): Research Grant or Support; Shionogi  Involved: Self): Research Grant or Support; Specific Diagnostics  Involved: Self): Research Grant or Support; Spero  Involved: Self): Research Grant or Support; SuperTrans Medical LT  Involved: Self): Research Grant or Support; T2 Biosystems  Involved: Self): Research Grant or Support; The University of Queensland  Involved: Self): Research Grant or Support; Thermo Fisher Scientific  Involved: Self): Research Grant or Support; Tufts Medical Center  Involved: Self): Research Grant or Support; Universite de Sherbrooke  Involved: Self): Research Grant or Support; University of Iowa  Involved: Self): Research Grant or Support; University of Iowa Hospitals and Clinics  Involved: Self): Research Grant or Support; University of Wisconsin  Involved: Self): Research Grant or Support; UNT System College of Pharmacy  Involved: Self): Research Grant or Support; URMC  Involved: Self): Research Grant or Support; UT Southwestern  Involved: Self): Research Grant or Support; VenatoRx  Involved: Self): Research Grant or Support; Viosera Therapeutics  Involved: Self): Research Grant or Support; Wayne State University  Involved: Self): Research Grant or Support


Enterobacterales isolates. The use of these agents led to an increase of carbapenem resistance among Enterobacterales. Monitoring isolates that carry β-lactamases is important to understand their prevalence and susceptibility to clinically available antimicrobial agents. We evaluated the prevalence of β-lactamases and the activity of antimicrobial agents against 1,209 isolates collected in 69 US hospitals.Carbapenems are broadly used for the treatment of ESBL-producing Enterobacterales isolates collected during 2019 were susceptibility (S) tested by reference broth microdilution methods. Isolates submitted to whole genome sequencing were: (1) Escherichia coli (EC) and Klebsiella pneumoniae  displaying MIC values ≥2 mg/L for at least 2 of the following β-lactams: ceftazidime, ceftriaxone, aztreonam, or cefepime; (2) Enterobacter cloacae (ECL) and Citrobacter spp.  displaying MIC values ≥16 mg/L for ceftazidime and/or ≥2 mg/L for cefepime; and (3) Enterobacterales (n=118) displaying elevated carbapenem (meropenem and/or imipenem) MIC results at >1 mg/L.A total of 9,686 blaCTX-M-15 (n=516), followed by blaCTX-M-14 (n=153). Most of these isolates were EC (278/147 for blaCTX-M-15/blaCTX-M-14), but 220 KPN harbored blaCTX-M-15. A total of 302 EC and KPN isolates carried blaOXA-1. Among ECL and CIT, blaCTX-M-15 and SHV genes encoding ESBLs were noted among 18 and 18 isolates. Carbapenemase genes were noted among 77 isolates, including 65 blaKPC, 3 blaSME, 6 blaOXA-48-like, and 3 blaNDM. Ceftazidime-avibactam (CAZ-AVI) was the only agent active against all ESBL-producers that did not carry carbapenemases (Table). CAZ-AVI was active against 90.9% of the isolates producing carbapenemases. Isolates resistant to this combination included 3 NDM-producers and 1 isolate harboring blaKPC-31.A total of 723 isolates harbored ESBL genes but did not carry carbapenemases. The most common ESBL gene was Enterobacterales isolates carrying ESBLs, mainly blaCTX-M-15, were very prevalent in this collection of US isolates. CAZ-AVI was very active against isolates tested, including isolates producing carbapenemases that displayed resistance to many comparator agents.Mariana Castanheira, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Qpex Biopharma (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, Affinity Biosensors  Involved: Self): Research Grant or Support; Allergan  Involved: Self): Research Grant or Support; Amicrobe, Inc  Involved: Self): Research Grant or Support; Amplyx Pharma  Involved: Self): Research Grant or Support; Artugen Therapeutics USA, Inc.  Involved: Self): Research Grant or Support; Astellas  Involved: Self): Research Grant or Support; Basilea  Involved: Self): Research Grant or Support; Beth Israel Deaconess Medical Center  Involved: Self): Research Grant or Support; BIDMC  Involved: Self): Research Grant or Support; bioMerieux Inc.  Involved: Self): Research Grant or Support; BioVersys Ag  Involved: Self): Research Grant or Support; Bugworks  Involved: Self): Research Grant or Support; Cidara  Involved: Self): Research Grant or Support; Cipla  Involved: Self): Research Grant or Support; Contrafect  Involved: Self): Research Grant or Support; Cormedix  Involved: Self): Research Grant or Support; Crestone, Inc.  Involved: Self): Research Grant or Support; Curza  Involved: Self): Research Grant or Support; CXC7  Involved: Self): Research Grant or Support; Entasis  Involved: Self): Research Grant or Support; Fedora Pharmaceutical  Involved: Self): Research Grant or Support; Fimbrion Therapeutics  Involved: Self): Research Grant or Support; Fox Chase  Involved: Self): Research Grant or Support; GlaxoSmithKline  Involved: Self): Research Grant or Support; Guardian Therapeutics  Involved: Self): Research Grant or Support; Hardy Diagnostics  Involved: Self): Research Grant or Support; IHMA  Involved: Self): Research Grant or Support; Janssen Research & Development  Involved: Self): Research Grant or Support; Johnson & Johnson  Involved: Self): Research Grant or Support; Kaleido Biosceinces  Involved: Self): Research Grant or Support; KBP Biosciences  Involved: Self): Research Grant or Support; Luminex  Involved: Self): Research Grant or Support; Matrivax  Involved: Self): Research Grant or Support; Mayo Clinic  Involved: Self): Research Grant or Support; Medpace  Involved: Self): Research Grant or Support; Meiji Seika Pharma Co., Ltd.  Involved: Self): Research Grant or Support; Melinta  Involved: Self): Research Grant or Support; Menarini  Involved: Self): Research Grant or Support; Merck  Involved: Self): Research Grant or Support; Meridian Bioscience Inc.  Involved: Self): Research Grant or Support; Micromyx  Involved: Self): Research Grant or Support; MicuRx  Involved: Self): Research Grant or Support; N8 Medical  Involved: Self): Research Grant or Support; Nabriva  Involved: Self): Research Grant or Support; National Institutes of Health  Involved: Self): Research Grant or Support; National University of Singapore  Involved: Self): Research Grant or Support; North Bristol NHS Trust  Involved: Self): Research Grant or Support; Novome Biotechnologies  Involved: Self): Research Grant or Support; Paratek  Involved: Self): Research Grant or Support; Pfizer  Involved: Self): Research Grant or Support; Prokaryotics Inc.  Involved: Self): Research Grant or Support; QPEX Biopharma  Involved: Self): Research Grant or Support; Rhode Island Hospital  Involved: Self): Research Grant or Support; RIHML  Involved: Self): Research Grant or Support; Roche  Involved: Self): Research Grant or Support; Roivant  Involved: Self): Research Grant or Support; Salvat  Involved: Self): Research Grant or Support; Scynexis  Involved: Self): Research Grant or Support; SeLux Diagnostics  Involved: Self): Research Grant or Support; Shionogi  Involved: Self): Research Grant or Support; Specific Diagnostics  Involved: Self): Research Grant or Support; Spero  Involved: Self): Research Grant or Support; SuperTrans Medical LT  Involved: Self): Research Grant or Support; T2 Biosystems  Involved: Self): Research Grant or Support; The University of Queensland  Involved: Self): Research Grant or Support; Thermo Fisher Scientific  Involved: Self): Research Grant or Support; Tufts Medical Center  Involved: Self): Research Grant or Support; Universite de Sherbrooke  Involved: Self): Research Grant or Support; University of Iowa  Involved: Self): Research Grant or Support; University of Iowa Hospitals and Clinics  Involved: Self): Research Grant or Support; University of Wisconsin  Involved: Self): Research Grant or Support; UNT System College of Pharmacy  Involved: Self): Research Grant or Support; URMC  Involved: Self): Research Grant or Support; UT Southwestern  Involved: Self): Research Grant or Support; VenatoRx  Involved: Self): Research Grant or Support; Viosera Therapeutics  Involved: Self): Research Grant or Support; Wayne State University  Involved: Self): Research Grant or Support Lalitagauri M. Deshpande, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Pfizer, Inc. (Research Grant or Support) Timothy B. Doyle, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)


Scientific Reports 10.1038/s41598-021-93017-x, published on 2 July 2021Correction to: The original version of this Article contained an error in Affiliation 1, which was incorrectly given as ‘Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology (GAIHST), Gachon University, Seongnam-si 13120, South Korea’. The correct affiliation is listed below.Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Korea.Additionally, this Article contained an error in the Acknowledgments section."This work was supported by Institute of Information & Communications Technology Planning & Evaluation (IITP) Grant funded by the Korea Government (MSIT) , and the GRRC program of Gyeonggi province. , and the Gachon Program (GCU-202008440010)."now reads:"This work was supported by Institute of Information & Communications Technology Planning & Evaluation (IITP) Grant funded by the Korea Government (MSIT) , and the GRRC program of Gyeonggi province. [GRRC-Gachon2020(B01)], AI-based Medical Image Analysis], and the Gachon Program (GCU-202106290001)."The original Article has been corrected.


Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), Haemophilus parainfluenzae (HP), methicillin-susceptible Staphylococcus aureus (MSSA), Escherichia coli (EC), Klebsiella pneumoniae (KPN), Pseudomonas aeruginosa (PSA), Chlamydia pneumoniae, Mycoplasma pneumoniae and L. pneumophila. In this study, the in vitro susceptibilities of DLX and comparator quinolones were determined for clinical isolates from CAP and CA-lower respiratory tract infections (LRTIs).Delafloxacin (DLX) is a broad-spectrum fluoroquinolone antibacterial approved in the US for the treatment of community-acquired bacterial pneumonia (CABP). DLX is indicated to treat CABP caused by CAP and CA-LRTI isolates were consecutively collected at 67 US medical centers participating in the SENTRY Surveillance Program during 2014-2020. Sites submitted 1 isolate per patient per infection episode. Isolate identification was determined at each site and confirmed using standard biochemical or molecular methods at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology. CLSI (2021) interpretive criteria were applied, FDA criteria were used for DLX. The susceptibility results for DLX, levofloxacin (LEV), moxifloxacin (MOX), and ciprofloxacin (CIP) for the indicated species are shown in the table. As MOX does not have CLSI breakpoints for EC, KPN, or PSA, CIP was tested for those species instead. DLX had the highest percent susceptibility against MSSA (91.8%). SPN and HI were >97% susceptible, and HP was >91% for all 3 drugs. KPN susceptibility ranged from 86.4% for LEV to 76.9% for DLX. Susceptibilities for EC and PSA were similar for the 3 drugs, EC varied from 59.8% for LEV to 57.0% for DLX, and PSA varied from 71.6% for CIP to 64.0% to LEV. in vitro results suggest that DLX may be a useful therapeutic option for CABP caused by Gram-positive, Gram-negative and fastidious pathogens.DLX had good activity against recent CAP and CA-LRTI isolates from US hospitals. DLX had the highest susceptibility of the quinolones tested against MSSA. Quinolone-resistant SPN and HI were uncommon. These Dee Shortridge, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support) Jennifer M. Streit, BS, GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Michael D. Huband, BS, AbbVie (formerly Allergan) (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support) Mariana Castanheira, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Qpex Biopharma (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, Affinity Biosensors  Involved: Self): Research Grant or Support; Allergan  Involved: Self): Research Grant or Support; Amicrobe, Inc  Involved: Self): Research Grant or Support; Amplyx Pharma  Involved: Self): Research Grant or Support; Artugen Therapeutics USA, Inc.  Involved: Self): Research Grant or Support; Astellas  Involved: Self): Research Grant or Support; Basilea  Involved: Self): Research Grant or Support; Beth Israel Deaconess Medical Center  Involved: Self): Research Grant or Support; BIDMC  Involved: Self): Research Grant or Support; bioMerieux Inc.  Involved: Self): Research Grant or Support; BioVersys Ag  Involved: Self): Research Grant or Support; Bugworks  Involved: Self): Research Grant or Support; Cidara  Involved: Self): Research Grant or Support; Cipla  Involved: Self): Research Grant or Support; Contrafect  Involved: Self): Research Grant or Support; Cormedix  Involved: Self): Research Grant or Support; Crestone, Inc.  Involved: Self): Research Grant or Support; Curza  Involved: Self): Research Grant or Support; CXC7  Involved: Self): Research Grant or Support; Entasis  Involved: Self): Research Grant or Support; Fedora Pharmaceutical  Involved: Self): Research Grant or Support; Fimbrion Therapeutics  Involved: Self): Research Grant or Support; Fox Chase  Involved: Self): Research Grant or Support; GlaxoSmithKline  Involved: Self): Research Grant or Support; Guardian Therapeutics  Involved: Self): Research Grant or Support; Hardy Diagnostics  Involved: Self): Research Grant or Support; IHMA  Involved: Self): Research Grant or Support; Janssen Research & Development  Involved: Self): Research Grant or Support; Johnson & Johnson  Involved: Self): Research Grant or Support; Kaleido Biosceinces  Involved: Self): Research Grant or Support; KBP Biosciences  Involved: Self): Research Grant or Support; Luminex  Involved: Self): Research Grant or Support; Matrivax  Involved: Self): Research Grant or Support; Mayo Clinic  Involved: Self): Research Grant or Support; Medpace  Involved: Self): Research Grant or Support; Meiji Seika Pharma Co., Ltd.  Involved: Self): Research Grant or Support; Melinta  Involved: Self): Research Grant or Support; Menarini  Involved: Self): Research Grant or Support; Merck  Involved: Self): Research Grant or Support; Meridian Bioscience Inc.  Involved: Self): Research Grant or Support; Micromyx  Involved: Self): Research Grant or Support; MicuRx  Involved: Self): Research Grant or Support; N8 Medical  Involved: Self): Research Grant or Support; Nabriva  Involved: Self): Research Grant or Support; National Institutes of Health  Involved: Self): Research Grant or Support; National University of Singapore  Involved: Self): Research Grant or Support; North Bristol NHS Trust  Involved: Self): Research Grant or Support; Novome Biotechnologies  Involved: Self): Research Grant or Support; Paratek  Involved: Self): Research Grant or Support; Pfizer  Involved: Self): Research Grant or Support; Prokaryotics Inc.  Involved: Self): Research Grant or Support; QPEX Biopharma  Involved: Self): Research Grant or Support; Rhode Island Hospital  Involved: Self): Research Grant or Support; RIHML  Involved: Self): Research Grant or Support; Roche  Involved: Self): Research Grant or Support; Roivant  Involved: Self): Research Grant or Support; Salvat  Involved: Self): Research Grant or Support; Scynexis  Involved: Self): Research Grant or Support; SeLux Diagnostics  Involved: Self): Research Grant or Support; Shionogi  Involved: Self): Research Grant or Support; Specific Diagnostics  Involved: Self): Research Grant or Support; Spero  Involved: Self): Research Grant or Support; SuperTrans Medical LT  Involved: Self): Research Grant or Support; T2 Biosystems  Involved: Self): Research Grant or Support; The University of Queensland  Involved: Self): Research Grant or Support; Thermo Fisher Scientific  Involved: Self): Research Grant or Support; Tufts Medical Center  Involved: Self): Research Grant or Support; Universite de Sherbrooke  Involved: Self): Research Grant or Support; University of Iowa  Involved: Self): Research Grant or Support; University of Iowa Hospitals and Clinics  Involved: Self): Research Grant or Support; University of Wisconsin  Involved: Self): Research Grant or Support; UNT System College of Pharmacy  Involved: Self): Research Grant or Support; URMC  Involved: Self): Research Grant or Support; UT Southwestern  Involved: Self): Research Grant or Support; VenatoRx  Involved: Self): Research Grant or Support; Viosera Therapeutics  Involved: Self): Research Grant or Support; Wayne State University  Involved: Self): Research Grant or Support


Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral prodrug that is converted to tebipenem (TBP), the active moiety. TBP is a carbapenem with activity against multidrug-resistant Gram-negative pathogens, including extended-spectrum-β-lactamase-producing Enterobacterales and is being developed for treating complicated urinary tract infections (cUTI) and acute pyelonephritis (AP). Data from three Phase 1 studies and one Phase 3 study in patients with cUTI/AP were used to develop a population pharmacokinetic (PPK) model for TBP and identify covariates that described the variability in TBP pharmacokinetics (PK).The PPK model was developed using TBP plasma and urine concentration-time data from the above-described Phase 1 and 3 studies. TBPPI-HBr doses, which ranged from 100 to 900 mg, were administered as single or multiple doses every 8 hours. After development of the structural model, stepwise forward and backward selection procedures were used to identify significant covariate relationships. The robustness of the final PPK model was assessed using a prediction-corrected visual predictive check (PC-VPC).The final dataset included 3448 plasma concentrations from 99 Phase 1 subjects and 647 Phase 3 patients and urine concentrations from 128 Phase 1 subjects. A two-compartment model with linear, first-order elimination and transit compartments to describe the rate of drug absorption after oral administration of TBP-PI-HBr best described TBP PK. The most clinically significant covariate effect, which would warrant dose adjustment, was the relationship between apparent oral clearance and creatinine clearance. In contrast, age, body size, sex, and fed status each had a minimal impact on TBP exposure. The PC-VPC showed good agreement between median simulated plasma concentrations based on the final PPK model and the median observed plasma concentrations for the pooled dataset .Figure 1. Prediction-corrected visual predictive check plot for the final population PK model using the pooled analysis datasetA robust description of TBP plasma PK in subjects and patients with cUTI/AP was achieved, such that derived measures of TBP plasma exposure are expected to be both accurate and precise. The population PK model was considered appropriate for model-based simulations and the assessment of PK-PD relationships for TBP.Harish Ganesan, M.S., 3-V Biosciences (Grant/Research Support)Achogen (Grant/Research Support)Amplyx Pharmaceuticals, Inc. (Grant/Research Support)Arixa Pharmaceuticals (Grant/Research Support)Arsanis Inc. (Grant/Research Support)B. Braun Medical Inc. (Grant/Research Support)Basilea Pharmaceutica (Grant/Research Support)BLC USA (Grant/Research Support)Boston Pharmaceuticals (Grant/Research Support)Bravos Biosciences, LLC (Grant/Research Support)Cidara Therapeutics Inc. (Grant/Research Support)Cipla, USA (Grant/Research Support)Corcept Therapeutics (Grant/Research Support)Cumberland Pharmaceuticals (Grant/Research Support)Debiopharm International SA (Grant/Research Support)Discuva Limited (Grant/Research Support)Emerald Lake Technologies (Grant/Research Support)Enhanced Pharmacodynamics (Grant/Research Support)Entasis Therapeutics (Grant/Research Support)E-Scape Bio (Grant/Research Support)Genentech (Grant/Research Support)Geom Therapeutics, Inc. (Grant/Research Support)GlaxoSmithKline (Grant/Research Support)Hoffmann-La Roche (Grant/Research Support)Horizon Orphan LLC (Grant/Research Support)ICPD Biosciences, LLC (Grant/Research Support)Indalo Therapeutics (Grant/Research Support)Insmed Inc. (Grant/Research Support)Institute for Clinical Pharmacodynamics (Employee)Iterum (Grant/Research Support)KBP Biosciences USA (Grant/Research Support)Kyoto Biopharma, Inc. (Grant/Research Support)Matinas (Grant/Research Support)Meiji Seika Pharma Co., Ltd. (Grant/Research Support)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche S.p.A. (Grant/Research Support)Merck & Co., Inc (Grant/Research Support)Mutabilis (Grant/Research Support)Nabriva Therapeutics AG (Grant/Research Support)Naeja-RGM Pharmaceuticals (Grant/Research Support)Nosopharm SAS (Grant/Research Support)Novartis Pharmaceuticals Corp. (Grant/Research Support)NuCana Biomed (Grant/Research Support)Paratek Pharmaceuticals, Inc. (Grant/Research Support)Polyphor, Ltd. (Grant/Research Support)Prothena Corporation (Grant/Research Support)PTC Therapeutics (Grant/Research Support)Rempex Pharmaceuticals (Grant/Research Support)Roche TCRC (Grant/Research Support)Sagimet (Grant/Research Support)scPharmaceuticals Inc. (Grant/Research Support)Scynexis (Grant/Research Support)Spero Therapeutics (Grant/Research Support)TauRx Therapeutics (Grant/Research Support)Tetraphase Pharmaceuticals (Grant/Research Support)Theravance Biopharma Pharmaceutica (Grant/Research Support)USCAST (Grant/Research Support)VenatoRx (Grant/Research Support)Vical Incorporated (Grant/Research Support)Wockhardt Bio AG (Grant/Research Support)Zavante Therapeutics (Grant/Research Support)Zogenix International (Grant/Research Support) Vipul Kumar, PhD, Spero Therapeutics  Sujata M. Bhavnani, Pharm.D., M.S., FIDSA, 3-V Biosciences (Grant/Research Support)Achogen (Grant/Research Support)Amplyx Pharmaceuticals, Inc. (Grant/Research Support)Arixa Pharmaceuticals (Grant/Research Support)Arsanis Inc. (Grant/Research Support)B. Braun Medical Inc. (Grant/Research Support)Basilea Pharmaceutica (Grant/Research Support)BLC USA (Grant/Research Support)Boston Pharmaceuticals (Grant/Research Support)Bravos Biosciences, LLC Cidara Therapeutics Inc. (Grant/Research Support)Cipla, USA (Grant/Research Support)Corcept Therapeutics (Grant/Research Support)Cumberland Pharmaceuticals (Grant/Research Support)Debiopharm International SA (Grant/Research Support)Discuva Limited (Grant/Research Support)Emerald Lake Technologies (Grant/Research Support)Enhanced Pharmacodynamics (Grant/Research Support)Entasis Therapeutics (Grant/Research Support)E-Scape Bio (Grant/Research Support)Genentech (Grant/Research Support)Geom Therapeutics, Inc. (Grant/Research Support)GlaxoSmithKline (Grant/Research Support)Hoffmann-La Roche (Grant/Research Support)Horizon Orphan LLC (Grant/Research Support)ICPD Biosciences, LLC Indalo Therapeutics (Grant/Research Support)Insmed Inc. (Grant/Research Support)Institute for Clinical Pharmacodynamics (Employee)Iterum (Grant/Research Support)KBP Biosciences USA (Grant/Research Support)Kyoto Biopharma, Inc. (Grant/Research Support)Matinas (Grant/Research Support)Meiji Seika Pharma Co., Ltd. (Grant/Research Support)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche S.p.A. (Grant/Research Support)Merck & Co., Inc (Grant/Research Support)Mutabilis (Grant/Research Support)Nabriva Therapeutics AG (Grant/Research Support)Naeja-RGM Pharmaceuticals (Grant/Research Support)Nosopharm SAS (Grant/Research Support)Novartis Pharmaceuticals Corp. (Grant/Research Support)NuCana Biomed (Grant/Research Support)Paratek Pharmaceuticals, Inc. (Grant/Research Support)Polyphor, Ltd. (Grant/Research Support)Prothena Corporation (Grant/Research Support)PTC Therapeutics (Grant/Research Support)Rempex Pharmaceuticals (Grant/Research Support)Roche TCRC (Grant/Research Support)Sagimet (Grant/Research Support)scPharmaceuticals Inc. (Grant/Research Support)Scynexis (Grant/Research Support)Spero Therapeutics (Grant/Research Support)TauRx Therapeutics (Grant/Research Support)Tetraphase Pharmaceuticals (Grant/Research Support)Theravance Biopharma Pharmaceutica (Grant/Research Support)USCAST (Grant/Research Support)VenatoRx (Grant/Research Support)Vical Incorporated (Grant/Research Support)Wockhardt Bio AG (Grant/Research Support)Zavante Therapeutics (Grant/Research Support)Zogenix International (Grant/Research Support) David Melnick, MD, Spero Therapeutics  Christopher M. Rubino, Pharm.D., 3-V Biosciences (Grant/Research Support)Achogen (Grant/Research Support)Amplyx Pharmaceuticals, Inc. (Grant/Research Support)Arixa Pharmaceuticals (Grant/Research Support)Arsanis Inc. (Grant/Research Support)B. Braun Medical Inc. (Grant/Research Support)Basilea Pharmaceutica (Grant/Research Support)BLC USA (Research Grant or Support)Boston Pharmaceuticals (Grant/Research Support)Bravos Biosciences, LLC Cidara Therapeutics Inc. (Grant/Research Support)Cipla, USA (Grant/Research Support)Corcept Therapeutics (Grant/Research Support)Cumberland Pharmaceuticals (Grant/Research Support)Debiopharm International SA (Grant/Research Support)Discuva Limited (Grant/Research Support)Emerald Lake Technologies (Grant/Research Support)Enhanced Pharmacodynamics (Grant/Research Support)Entasis Therapeutics (Grant/Research Support)E-Scape Bio (Grant/Research Support)Genentech (Grant/Research Support)Geom Therapeutics, Inc. (Grant/Research Support)GlaxoSmithKline (Grant/Research Support)Hoffmann-La Roche (Grant/Research Support)Horizon Orphan LLC (Grant/Research Support)ICPD Biosciences, LLC Indalo Therapeutics (Grant/Research Support)Insmed Inc. (Grant/Research Support)Institute for Clinical Pharmacodynamics (Employee)Iterum (Grant/Research Support)KBP Biosciences USA (Grant/Research Support)Kyoto Biopharma, Inc. (Grant/Research Support)Matinas (Grant/Research Support)Meiji Seika Pharma Co., Ltd. (Grant/Research Support)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche S.p.A. (Grant/Research Support)Merck & Co., Inc (Grant/Research Support)Mutabilis (Grant/Research Support)Nabriva Therapeutics AG (Grant/Research Support)Naeja-RGM Pharmaceuticals (Grant/Research Support)Nosopharm SAS (Grant/Research Support)Novartis Pharmaceuticals Corp. (Grant/Research Support)NuCana Biomed (Grant/Research Support)Paratek Pharmaceuticals, Inc. (Grant/Research Support)Polyphor, Ltd. (Grant/Research Support)Prothena Corporation (Grant/Research Support)PTC Therapeutics (Grant/Research Support)Rempex Pharmaceuticals (Grant/Research Support)Roche TCRC (Grant/Research Support)Sagimet (Grant/Research Support)scPharmaceuticals Inc. (Grant/Research Support)Scynexis (Grant/Research Support)Spero Therapeutics (Grant/Research Support)TauRx Therapeutics (Grant/Research Support)Tetraphase Pharmaceuticals (Grant/Research Support)Theravance Biopharma Pharmaceutica (Grant/Research Support)USCAST (Grant/Research Support)VenatoRx (Grant/Research Support)Vical Incorporated (Grant/Research Support)Wockhardt Bio AG (Grant/Research Support)Zavante Therapeutics (Grant/Research Support)Zogenix International (Grant/Research Support)


The authors regret that there was an error in the calculation of the PF-10 score used in analysis. The affected the data presented in Tables 2 and 4, which have been updated below.The authors would like to apologise for any inconvenience caused.Table 2 Linear regression association of HRQOL measured using the PF-10 and HAQ-DI with gout and co-morbid characteristicsTable 4 Linear regression association of HRQOL measured using the PF-10 and HAQ-DI with sociodemographic characteristics.Abbreviations: CI: Confidence Interval; TIA: Transient Ischaemic Attack; MI: Myocardial Infarction; BMI: Body Mass Index; PF-10: Physical Function 10; HAQ-DI: Health Assessment Questionnaire Disability Index; CI: Confidence Interval.aAdjusted for comorbid and socio-demographic characteristics; b Adjusted for gout and socio-demographic characteristics; c Adjusted for gout and comorbid characteristics.


FFC-AL-EIT was implemented by a Research Nurse Facilitator working with a community champion and stakeholder team for 12 months to increase function and physical activity among residents. FFC-AL-EIT included four steps: (Step I) Environment and Policy Assessments; (Step II) Education; (Step III) Establishing Resident Function Focused Care Service Plans; and (Step IV) Mentoring and Motivating. A total of 85 communities and 794 residents were included. The age of participants was 89.48 (SD=7.43), the majority was female  and white . Resident measures, obtained at baseline, four and 12 months, included function, physical activity, and performance of function focused care. Setting outcomes, obtained at baseline and 12 months, included environment and policy assessments and service plans. Effectiveness was based on less decline in function (p<.001), more function focused care (p=.012) and better environment (p=.032) and policy (p=.003) support for function focused care in treatment sites.


Scientific Reportshttps://doi.org/10.1038/s41598-021-00144-6, published online 19 October 2021Correction to: The Funding section in the original version of this Article was omitted. The Funding section now reads:“The following authors are supported by grants from the British Heart Foundation (BHF): YL & KR (grant number: FS/PhD/21/29110) and KR & DC (grant number: PG/18/65/33872); KR is also in receipt of funding from the UKRI’s Global Challenges Research Fund (GCRF), Grant Ref ES/P0110551/1, Oxford NIHR Biomedical Research Centre and the Oxford Martin School (OMS), University of Oxford. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and not necessarily those of the OMS, the BHF, the GCRF, the NIHR or the Department of Health and Social Care.”The original Article has been corrected.


The correct citation is: Hao S, Snyder RA, Irish W, Parikh AA (2021) Association of race and health insurance in treatment disparities of colon cancer: A retrospective analysis utilizing a national hospital-based database in the United States. PLoS Med 18(10): e1003842.


Following the publication of the original article , errors bold typeface.The changes have been highlighted in Reference26642: 2010(E).[20] Food Products-Determination of the glycaemic index (GI) and recommendation for food classification. ISO


In the original article, we neglected to include the grant number for the funder Fundamental Research Funds for the Central Universities. The grant number is SWU020014 to Hongyan Xu. The corrected funding statement appears below.FUNDING“This research work was supported by grants from the National Natural Science Foundation of China (31873035), the Fundamental Research Funds for the Central Universities (SWU020014 to HX) (2021), Science and Technology Program of Guangzhou (201904010172), Social Public Welfare Research (2019HY-XKQ02), Open Project of State Key Laboratory of Freshwater Ecology and Biotechnology (2019FB01), Central Public-interest Scientific Institution Basal Research Fund, CAFS , Guangdong Agricultural Research System, Grant/Award Number (2019KJ150), China-ASEAN Maritime Cooperation Fund (CAMC-2018F), International Agricultural Exchange and Cooperation (2130114), Science and Technology Program of Guangdong Provincial, Grant/Award Number (2019B030316029), and National Freshwater Genetic Resource Center (NFGR-2020).”2, Yulin Li2, Xinping Zhu1,” it should be “Xiaoli Liu1,2, Wei Li2, Yanping Yang2, Kaili Chen1, Yulin Li1, Xinping Zhu2, Hua Ye1 and Hongyan Xu1,2.”In the published article, there was an error in affiliations for authors Kaili Chen, Yulin Li, and Xinping Zhu. Instead of “Kaili ChenThe authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.


Enterobacter spp. are part of the ESKAPE pathogens that have been recognized as a threat to human health. Among this genus, E. cloacae species complex (ECL) is the most common species that causes human infections. ECL can develop resistance to ß-lactams and other antimicrobial classes due to alterations in gene regulatory pathways. We evaluated the activity of meropenem-vaborbactam, ceftazidime-avibactam, and comparator agents against 235 multidrug resistant (MDR) ECL isolates collected in Europe and the US during 2017-2019.A total of 2,459 ECL clinical isolates were collected in 40 European and 33 US hospitals. Isolates were susceptibility tested by reference broth microdilution methods and results were interpreted using CLSI, EUCAST, and US FDA breakpoints. MDR was defined as resistant to 3 or more drug classes when applying the CLSI breakpoints.MDR ECL were observed among 9.6% of the overall isolates. The MDR rate in Europe  was considerably higher than in the US . Meropenem-vaborbactam inhibited 94.5% and 97.4% of the MDR ECL isolates applying CLSI and EUCAST breakpoints, respectively (Table). Meropenem inhibited 77.9%/85.5% of the isolates (CLSI/EUCAST breakpoints). Cefepime inhibited only 26.0%/16.2% of the MDR ECL isolates while piperacillin-tazobactam inhibited only 13.2%/6.4%. Ceftazidime-avibactam inhibited 93.6% of the MDR ECL isolates. Amikacin and tigecycline were the most active non-beta-lactam comparators, inhibiting 91.9% and 80.0% of these isolates using CLSI/US FDA breakpoints. A total of 93.1% of the isolates were intermediate to colistin applying CLSI breakpoints or susceptible using the EUCAST criteria. Meropenem-vaborbactam inhibited 73.5% and 87.8% of the MDR ECL isolates nonsusceptible to meropenem and cefepime, the main therapeutic option against ECL isolates. Ceftazidime-avibactam inhibited 73.5% of these isolates.Enterobacterales species/species complex displaying MDR and carbapenem-resistance phenotypes, behind only Klebsiella pneumoniae. Meropenem-vaborbactam and ceftazidime-avibactam can be important options to treat infections caused by MDR ECL.In a global surveillance, ECL is the second most common Mariana Castanheira, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Qpex Biopharma (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, Affinity Biosensors  Involved: Self): Research Grant or Support; Allergan  Involved: Self): Research Grant or Support; Amicrobe, Inc  Involved: Self): Research Grant or Support; Amplyx Pharma  Involved: Self): Research Grant or Support; Artugen Therapeutics USA, Inc.  Involved: Self): Research Grant or Support; Astellas  Involved: Self): Research Grant or Support; Basilea  Involved: Self): Research Grant or Support; Beth Israel Deaconess Medical Center  Involved: Self): Research Grant or Support; BIDMC  Involved: Self): Research Grant or Support; bioMerieux Inc.  Involved: Self): Research Grant or Support; BioVersys Ag  Involved: Self): Research Grant or Support; Bugworks  Involved: Self): Research Grant or Support; Cidara  Involved: Self): Research Grant or Support; Cipla  Involved: Self): Research Grant or Support; Contrafect  Involved: Self): Research Grant or Support; Cormedix  Involved: Self): Research Grant or Support; Crestone, Inc.  Involved: Self): Research Grant or Support; Curza  Involved: Self): Research Grant or Support; CXC7  Involved: Self): Research Grant or Support; Entasis  Involved: Self): Research Grant or Support; Fedora Pharmaceutical  Involved: Self): Research Grant or Support; Fimbrion Therapeutics  Involved: Self): Research Grant or Support; Fox Chase  Involved: Self): Research Grant or Support; GlaxoSmithKline  Involved: Self): Research Grant or Support; Guardian Therapeutics  Involved: Self): Research Grant or Support; Hardy Diagnostics  Involved: Self): Research Grant or Support; IHMA  Involved: Self): Research Grant or Support; Janssen Research & Development  Involved: Self): Research Grant or Support; Johnson & Johnson  Involved: Self): Research Grant or Support; Kaleido Biosceinces  Involved: Self): Research Grant or Support; KBP Biosciences  Involved: Self): Research Grant or Support; Luminex  Involved: Self): Research Grant or Support; Matrivax  Involved: Self): Research Grant or Support; Mayo Clinic  Involved: Self): Research Grant or Support; Medpace  Involved: Self): Research Grant or Support; Meiji Seika Pharma Co., Ltd.  Involved: Self): Research Grant or Support; Melinta  Involved: Self): Research Grant or Support; Menarini  Involved: Self): Research Grant or Support; Merck  Involved: Self): Research Grant or Support; Meridian Bioscience Inc.  Involved: Self): Research Grant or Support; Micromyx  Involved: Self): Research Grant or Support; MicuRx  Involved: Self): Research Grant or Support; N8 Medical  Involved: Self): Research Grant or Support; Nabriva  Involved: Self): Research Grant or Support; National Institutes of Health  Involved: Self): Research Grant or Support; National University of Singapore  Involved: Self): Research Grant or Support; North Bristol NHS Trust  Involved: Self): Research Grant or Support; Novome Biotechnologies  Involved: Self): Research Grant or Support; Paratek  Involved: Self): Research Grant or Support; Pfizer  Involved: Self): Research Grant or Support; Prokaryotics Inc.  Involved: Self): Research Grant or Support; QPEX Biopharma  Involved: Self): Research Grant or Support; Rhode Island Hospital  Involved: Self): Research Grant or Support; RIHML  Involved: Self): Research Grant or Support; Roche  Involved: Self): Research Grant or Support; Roivant  Involved: Self): Research Grant or Support; Salvat  Involved: Self): Research Grant or Support; Scynexis  Involved: Self): Research Grant or Support; SeLux Diagnostics  Involved: Self): Research Grant or Support; Shionogi  Involved: Self): Research Grant or Support; Specific Diagnostics  Involved: Self): Research Grant or Support; Spero  Involved: Self): Research Grant or Support; SuperTrans Medical LT  Involved: Self): Research Grant or Support; T2 Biosystems  Involved: Self): Research Grant or Support; The University of Queensland  Involved: Self): Research Grant or Support; Thermo Fisher Scientific  Involved: Self): Research Grant or Support; Tufts Medical Center  Involved: Self): Research Grant or Support; Universite de Sherbrooke  Involved: Self): Research Grant or Support; University of Iowa  Involved: Self): Research Grant or Support; University of Iowa Hospitals and Clinics  Involved: Self): Research Grant or Support; University of Wisconsin  Involved: Self): Research Grant or Support; UNT System College of Pharmacy  Involved: Self): Research Grant or Support; URMC  Involved: Self): Research Grant or Support; UT Southwestern  Involved: Self): Research Grant or Support; VenatoRx  Involved: Self): Research Grant or Support; Viosera Therapeutics  Involved: Self): Research Grant or Support; Wayne State University  Involved: Self): Research Grant or Support Jennifer M. Streit, BS, GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Dee Shortridge, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support)


Correction to: BMC Geriatr 21, 105 (2021)https://doi.org/10.1186/s12877-020-01976-zhttps://me-we.eu/the-project/), as follows:Funding: “The study was conducted in the framework of the ME-WE project, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 754702. This work was also partially supported by Ricerca Corrente funding from Italian Ministry of Health to IRCCS INRCA. This funding body did not play any role in designing the study nor in data collection, analysis and interpretation, nor in writing this paper”.www.me-we.eu), namely: Linnaeus University (Sweden), coordinator; Eurocarers (Belgium); University of Sussex (United Kingdom); Carers Trust (United Kingdom); Kalaidos University of Applied Sciences (Switzerland); Netherlands Institute for Social Research (Netherlands); Vilans (Netherlands); National Institute of Health and Science on Ageing (IRCCS INRCA) ; Anziani e Non Solo ; University of Ljubljana (Slovenia).”Acknowledgements: “The authors would like to thank researchers, professionals and organisations who contributed to the ME-WE project. In particular, the authors thank the partner organisations of the ME-WE project (After publication of this article , the autThe original article  has been


Scientific Reports 10.1038/s41598-021-85489-8, published online 15 March 2021Correction to: The Acknowledgements section in the original version of this Article was incomplete.“This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2018R1D1A1B07044100) and the Institute of Information & Communications, Technology Planning & Evaluation (IITP) grant funded by the Korean government (2017-0-00855).”now reads:“This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2018R1D1A1B07044100) and the Institute of Information & Communications, Technology Planning & Evaluation (IITP) grant funded by the Korean government (2017-0-00855). This work was supported by the Research Grant of Kwangwoon University in 2020."The original Article has been corrected.


Nature Communications 10.1038/s41467-020-16741-4, published online 05 June 2020.Correction to: In the original version of the published article, several funding sources were omitted from the “Acknowledgements” section. The correct acknowledgement paragraph is:This work is based upon research conducted at the Northeastern Collaborative Access Team beamlines, which are funded by the National Institute of General Medical Sciences from the National Institutes of Health (P30 GM124165). The Eiger 16M detector on 24-ID-E is funded by an NIH-ORIP HEI grant (S10OD021527). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. We would also like to thank Dr. Laura Murray for help in cloning and crystallizing the G and U mutants, Gabriele Drews for technical assistance, and Dr. Olga Fedorova for the critical reading of the manuscript. We also thank all members of the Marcia, Pyle, and De Vivo labs for helpful discussion. Work in the Marcia lab is partly funded by the Agence Nationale de la Recherche (ANR-15-CE11-0003-01), by the Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) (ECTZ18552), by ITMO Cancer (18CN047-00), and by the Fondation ARC pour la recherche sur le cancer (PJA20191209284). The Marcia lab uses the platforms of the Grenoble Instruct Center (ISBG: UMS 3518 CNRS-CEA-UJF-EMBL) with support from FRISBI (ANR-10-INSB-05-02) and GRAL (ANR-10-LABX-49-01) within the Grenoble Partnership for Structural Biology (PSB). M.D.V. thanks the Italian Association for Cancer Research (AIRC) for financial support (IG 23679). A.M.P. is a Howard Hughes Medical Institute investigator.This has now been corrected in both the PDF and HTML versions of the Article.


Scientific Reports 10.1038/s41598-020-78814-0, published online 13 January 2021Correction to: The Acknowledgements section in this Article is incomplete."National Science Foundation of China (NSFC) (11604079); Science and Technology Program of Henan Province (192102210198); China Postdoctoral Science Foundation funded project (2018M632793); Foundation for University Young Key Teacher Program by Henan Province, China (2017GGJS155); Doctoral Fund Project of Henan Institute of Engineering (D2017023); the Key Scientific Research Projects of Institutions of Higher Learning in Henan Province (20A140006)."should read:"National Science Foundation of China (NSFC) (11604079); Science and Technology Program of Henan Province (192102210198 and 212102310903); China Postdoctoral Science Foundation funded project (2018M632793); Foundation for University Young Key Teacher Program by Henan Province, China (2017GGJS155); Doctoral Fund Project of Henan Institute of Engineering (D2017023); the Key Scientific Research Projects of Institutions of Higher Learning in Henan Province (20A140006)."


Scientific Reports 10.1038/s41598-021-02404-x, published online 30 November 2021Correction to: The Acknowledgements section in the original version of this Article was incomplete.“This work was supported by Open Research Fund of Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs (ZJK202101), Central Public-interest Scientific Institution Basal Research Fund, .”now reads:“This work was supported by Open Research Fund of Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs (ZJK202101), Central Public-interest Scientific Institution Basal Research Fund,  and National Key Research and Development Program of China (No. 2017YFC1600704)."The original Article has been corrected.


Enterobacterales (CNSE) produce carbapenemases, but some isolates do not carry these enzymes. Ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MBV), and imipenem-relebactam (IMR) have activity against CNSE isolates producing serine-carbapenemases, but these agents might have variable activity against isolates that do not produce these enzymes. We evaluated the activity of these agents against a collection of 170 carbapenemase-negative CNSE collected during 5 years in US hospitals.Most carbapenem-nonsusceptible Enterobacterales isolates  collected in US hospitals from 2016-2020 were susceptibility (S) tested by reference broth microdilution methods. Results were interpreted using CLSI 2020 breakpoints. CNSE displayed nonsusceptible (NS) MICs for imipenem or meropenem. CNSE isolates were screened for carbapenemase genes using whole genome sequencing.K. aerogenes (n=42), K. pneumoniae (32), and E. cloacae (32), but 13 other species also were carbapenemase negative. CAZ-AVI inhibited all carbapenemase-negative CNSE isolates . MBV and IMR inhibited 97.6% and 92.3% of the isolates. Amikacin (AMK) and tigecycline (TIG) inhibited 97.1% and 93.5%, while levofloxacin and meropenem (MEM) inhibited 63.5% and 64.7%. A total of 141 (82.9%) isolates were nonsusceptible (NS) to imipenem. When MEM NS isolates (n=60) were analysed separately, the S rates were lower for all agents except CAZ-AVI. CAZ-AVI inhibited all MEM NS carbapenemase-negative CNSE isolates. MBV and IMR inhibited 93.1% and 89.7% of these isolates, respectively. AMK and TIG inhibited 93.3% and 88.3%, respectively. Only 8.3% of the isolates were resistant to colistin.Among 685 (1.4% of the isolates) CNSE, 170 (24.8% of the CNSE) isolates did not produce carbapenemases. Most of these isolates were CAZ-AVI displayed good activity against carbapenemase-negative CNSE isolates, including all MEM NS that displayed greater resistance rates against all comparator agents. High-risk patients with infections caused by CNSE have an increased mortality rate compared to isolates susceptible to these agents. Implementation of appropriate therapy for these isolates is critical.Mariana Castanheira, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Qpex Biopharma (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, Affinity Biosensors  Involved: Self): Research Grant or Support; Allergan  Involved: Self): Research Grant or Support; Amicrobe, Inc  Involved: Self): Research Grant or Support; Amplyx Pharma  Involved: Self): Research Grant or Support; Artugen Therapeutics USA, Inc.  Involved: Self): Research Grant or Support; Astellas  Involved: Self): Research Grant or Support; Basilea  Involved: Self): Research Grant or Support; Beth Israel Deaconess Medical Center  Involved: Self): Research Grant or Support; BIDMC  Involved: Self): Research Grant or Support; bioMerieux Inc.  Involved: Self): Research Grant or Support; BioVersys Ag  Involved: Self): Research Grant or Support; Bugworks  Involved: Self): Research Grant or Support; Cidara  Involved: Self): Research Grant or Support; Cipla  Involved: Self): Research Grant or Support; Contrafect  Involved: Self): Research Grant or Support; Cormedix  Involved: Self): Research Grant or Support; Crestone, Inc.  Involved: Self): Research Grant or Support; Curza  Involved: Self): Research Grant or Support; CXC7  Involved: Self): Research Grant or Support; Entasis  Involved: Self): Research Grant or Support; Fedora Pharmaceutical  Involved: Self): Research Grant or Support; Fimbrion Therapeutics  Involved: Self): Research Grant or Support; Fox Chase  Involved: Self): Research Grant or Support; GlaxoSmithKline  Involved: Self): Research Grant or Support; Guardian Therapeutics  Involved: Self): Research Grant or Support; Hardy Diagnostics  Involved: Self): Research Grant or Support; IHMA  Involved: Self): Research Grant or Support; Janssen Research & Development  Involved: Self): Research Grant or Support; Johnson & Johnson  Involved: Self): Research Grant or Support; Kaleido Biosceinces  Involved: Self): Research Grant or Support; KBP Biosciences  Involved: Self): Research Grant or Support; Luminex  Involved: Self): Research Grant or Support; Matrivax  Involved: Self): Research Grant or Support; Mayo Clinic  Involved: Self): Research Grant or Support; Medpace  Involved: Self): Research Grant or Support; Meiji Seika Pharma Co., Ltd.  Involved: Self): Research Grant or Support; Melinta  Involved: Self): Research Grant or Support; Menarini  Involved: Self): Research Grant or Support; Merck  Involved: Self): Research Grant or Support; Meridian Bioscience Inc.  Involved: Self): Research Grant or Support; Micromyx  Involved: Self): Research Grant or Support; MicuRx  Involved: Self): Research Grant or Support; N8 Medical  Involved: Self): Research Grant or Support; Nabriva  Involved: Self): Research Grant or Support; National Institutes of Health  Involved: Self): Research Grant or Support; National University of Singapore  Involved: Self): Research Grant or Support; North Bristol NHS Trust  Involved: Self): Research Grant or Support; Novome Biotechnologies  Involved: Self): Research Grant or Support; Paratek  Involved: Self): Research Grant or Support; Pfizer  Involved: Self): Research Grant or Support; Prokaryotics Inc.  Involved: Self): Research Grant or Support; QPEX Biopharma  Involved: Self): Research Grant or Support; Rhode Island Hospital  Involved: Self): Research Grant or Support; RIHML  Involved: Self): Research Grant or Support; Roche  Involved: Self): Research Grant or Support; Roivant  Involved: Self): Research Grant or Support; Salvat  Involved: Self): Research Grant or Support; Scynexis  Involved: Self): Research Grant or Support; SeLux Diagnostics  Involved: Self): Research Grant or Support; Shionogi  Involved: Self): Research Grant or Support; Specific Diagnostics  Involved: Self): Research Grant or Support; Spero  Involved: Self): Research Grant or Support; SuperTrans Medical LT  Involved: Self): Research Grant or Support; T2 Biosystems  Involved: Self): Research Grant or Support; The University of Queensland  Involved: Self): Research Grant or Support; Thermo Fisher Scientific  Involved: Self): Research Grant or Support; Tufts Medical Center  Involved: Self): Research Grant or Support; Universite de Sherbrooke  Involved: Self): Research Grant or Support; University of Iowa  Involved: Self): Research Grant or Support; University of Iowa Hospitals and Clinics  Involved: Self): Research Grant or Support; University of Wisconsin  Involved: Self): Research Grant or Support; UNT System College of Pharmacy  Involved: Self): Research Grant or Support; URMC  Involved: Self): Research Grant or Support; UT Southwestern  Involved: Self): Research Grant or Support; VenatoRx  Involved: Self): Research Grant or Support; Viosera Therapeutics  Involved: Self): Research Grant or Support; Wayne State University  Involved: Self): Research Grant or Support Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)


Volume 5 of Learning Health Systems. An open access publication, the journal has advanced research and scholarship on learning health systems in partnership with our reviewers. With indexing in multiple major sources, we believe the journal is now on a sustainable, positive trajectory.The publication of Issue 4 marks the completion of The journal has also published five Special Issues: “Patient Empowerment and the Learning Health System” (v.1); “Ethical, Legal, and Social Implications of Learning Health Systems” (v.2); “Learning Health Systems: Connecting Research To Practice Worldwide” (v.3); “Human Phenomics and the Learning Health System” (v.4); and “Collaborative Learning Health Systems: Science and Practice” (v.5). Our talented guest editors have been instrumental in helping these Special Issues come to fruition.We are keenly aware that these achievements would not have happened without the dedicated efforts and insightful comments of all those individuals who accepted invitations to review submitted articles. With busy schedules and full commitments in the midst of the Covid‐19 pandemic, these individuals found the time and energy to contribute their expertise to our authors to help ensure that their papers met (and often exceeded) the journal's high standards for publication.Please accept our sincere gratitude for your outstanding efforts.Charles P. Friedman, Editor in Chief.The following list also includes reviewers of rejected manuscripts.Julia Adler‐Milstein (United States)John Ainsworth (United Kingdom of Great Britain and Northern Ireland)Jill Allison (Canada)Holt Anderson (United States)Anna Andreasson (Sweden)Patrick Archambault (Canada)Panagiotis Balatsoukas (United Kingdom of Great Britain and Northern Ireland)Maren Batalden (United States)Marc Berger (United States)Jeff Brown (United States)Julie Bynum (United States)Elizabeth Cohn (United States)Heather Colvin (United States)Derek Corrigan (Ireland)Benoit Cossette (Canada)Mary Costello (United States)Susan Cronin (United States)Jennie David (United States)Brendan Delaney (United Kingdom of Great Britain and Northern Ireland)Jordan Everson (United States)Rhonda Facile (United States)Marcy Fitz‐Randolph (United States)Thomas Foley (United Kingdom of Great Britain and Northern Ireland)Masanori Fukushima (Japan)Sarah Greene (United States)W. Ed Hammond (United States)Lamiece Hassan (United Kingdom of Great Britain and Northern Ireland)Frank Hulstaert (Belgium)Michael Ibara (United States)Amy Kilbourne (United States)Harold Lehmann (United States)Leslie Lenert (United States)David McCallie (United States)Loretta McCormick (Canada)Marianne McPherson (United States)Subha Madhavan (United States)Laura Merson (United Kingdom of Great Britain and Northern Ireland)Stephanie Morain (United States)Jessica Moreau (United States)Mark Musen (United States)Eileen Navarro (United States)Sally Okun (United States)Nancy Pandhi (United States)Richard Platt (United States)David Purcell (United States)Rohit Ramaswamy (United States)Barbara Rath (United States)Joshua Rubin (United States)Elin Salmiranta (Sweden)Edgar Schein (United States)Madeline Schmitt (United States)Michael Seid (United States)Archana Tapuria (United Kingdom of Great Britain and Northern Ireland)Jody Traver (United States)Robert Verheij (Netherlands)Jim Walker (United States)Chris Webb (United States)John Wilbanks (United States)David Williams (United States)Tracy Ziolek (United States)


N-tert-butyloxycarbonyl (N-Boc) group using oxalyl chloride’ by Nathaniel George et al., RSC Adv., 2020, 10, 24017–24026, DOI: 10.1039/D0RA04110F.Correction for ‘Mild deprotection of the  The authors regret the omission of a funding acknowledgement in the original article. This acknowledgement is given below.The authors acknowledge support of the Center for Pharmaceutical Research and Innovation (NIH P20 GM130456).The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.