scholarly journals 1443. Activity of Ceftazidime-Avibactam against Carbapemenase-negative Carbapenem-resistant Enterobacterales (CRE) Isolates from US Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S725-S725
Author(s):  
Mariana Castanheira ◽  
Timothy B Doyle ◽  
Cory Hubler ◽  
Rodrigo E Mendes ◽  
Helio S Sader
Keyword(s):  
Resistance Mechanisms ◽  
Chemical Diversity ◽  
Services Research ◽  
New Agents ◽  
E Coli ◽  
Department Of Health ◽  
Carbapenem Resistant ◽  
Center Research ◽  
Research Grant

Abstract Background Most CRE isolates in US hospitals produce KPC enzymes, but some do not carry carbapenemases. We investigated the prevalence, resistance mechanisms and activity of ceftazidime-avibactam and comparator agents against CRE that did not carry carbapenemase genes from US hospitals. Additionally, meropenem-resistant isolates were tested for meropenem-vaborbactam. Methods A total of 28,904 Enterobacterales isolates were collected in 70 US hospitals during 2016-2018, and susceptibility tested by reference broth microdilution. Meropenem-vaborbactam was tested using lyophilized panels following the manufacturer’s instructions. CRE isolates were submitted to whole genome sequencing for the screening of b-lactamase genes, multilocus sequence typing, changes in outer membrane protein (OMP) genes and AmpC expression levels. Results A total of 304 (1.1%) CREs were observed in the study period and 45 (14.8%) isolates did not carry carbapenemases. These isolates were mainly Klebsiella aerogenes, Enterobacter cloacae and Klebsiella pneumoniae (11, 11 and 10 isolates, respectively), but also included 5 other species. Acquired b-lactamase genes were detected among 17 isolates and blaCTX-M-15 was the most common (13 isolates). All K. aerogenes and 10 E. cloacae did not carry acquired b-lactamase genes. Ceftazidime-avibactam (100% susceptible) inhibited all isolates at the current breakpoint, followed by tigecycline and amikacin (> 80% susceptible). Other comparators were not active against non-carbapenemase-producing CRE. Nine of 35 meropenem-resistant isolates displayed meropenem-vaborbactam MIC values of ≥ 8 mg/L (nonsusceptible). Further analysis showed that 23 isolates had disruption of OmpC/OmpK36, 4 had disrupted OmpF/OmpK35 and 13 had both OMP genes disrupted. Additionally, 7 isolates had elevated AmpC expression among 17 isolates tested. Among 7 E. coli, 4 were ST131 and only 2 of 10 K. pneumoniae were clonal complex 11. Conclusion Therapy options for treatment of infections caused by CRE were very limited until recent approval of new agents with activity against these isolates. Ceftazidime-avibactam demonstrated full in vitro activity against all carbapenemase-negative CRE carrying multiple resistance mechanisms. Disclosures Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Cory Hubler, Allergan (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals 1629. Vancomycin Resistance in Enterococcus faecium Clinical Isolates Responsible for Bloodstream Infections in US Hospitals Over Ten Years (2010-2019) and Activity of Oritavancin

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S806-S807
Author(s):  
Cecilia G Carvalhaes ◽  
Helio S Sader ◽  
Jennifer M Streit ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes
Keyword(s):  
Enterococcus Faecium ◽  
Bloodstream Infections ◽  
Chemical Diversity ◽  
Intrinsic Resistance ◽  
Services Research ◽  
Vana Gene ◽  
Department Of Health ◽  
Common Phenotype ◽  
Center Research ◽  
Research Grant

Abstract Background Enterococcus faecium (EFM) causes difficult-to-treat infections due to its intrinsic resistance (R) and ability to acquire R to many antimicrobials. This study evaluated the vancomycin (VAN)-R rates over time and the activity of oritavancin (ORI) against a collection of EFM causing bloodstream infections (BSI). Methods A total of 1,081 BSI EFM isolates collected from 36 US hospitals in a prevalence mode design during 2010-2019 were evaluated. Bacterial identification was confirmed by MALDI-TOF MS. Susceptibility testing was performed by reference broth microdilution. For comparison, the ORI breakpoint for VAN-susceptible E. faecalis was applied to EFM. Isolates were characterized as VanA or VanB phenotypes based on their susceptibility (S) to VAN and teicoplanin (TEC). The VanB phenotype was confirmed by PCR and/or whole genome sequencing. Results Overall, 72.3% (782/1,081) of EFM were VAN-R (Table). VanA was the most common phenotype (97.7%; 764/782). The yearly VAN-R rates decreased from 81.8% in 2010 to 58.7% in 2019. A total of 18 (2.3%) isolates exhibited a VanB phenotype (TEC MIC, 0.5-8 mg/L); however, the vanB gene only was confirmed in 9 EFM isolates (TEC MIC, 0.5-1 mg/L), which were all collected in 2010-2012. The remaining 9 (50.0%) VanB phenotype EFM isolates carried a vanA gene (TEC MIC, 4-8 mg/L). ORI was very active against VAN-susceptible EFM (MIC50/90, ≤ 0.008/≤0.008/mg/L), VanA (MIC50/90, 0.03/0.12 mg/L; MIC100, 0.5 mg/L), and VanB (MIC50/90, ≤ 0.008/0.015 mg/L; MIC100, 0.03 mg/L) subsets. Only linezolid (LZD) and ORI (MIC, ≤ 0.12 mg/L) showed > 95.0%S against EFM and VAN-R subsets. Daptomycin (DAP)-R rarely was observed (0.8%), but it was more frequently found in the last 5 years. However, 49.9% of EFM isolates showed elevated DAP MICs (2 and 4 mg/L). ORI inhibited 77.8%, and 100.0% of DAP-R and LZD-nonsusceptible EFM isolates at ≤ 0.12 mg/L, respectively. Conclusion VAN-R rates among EFM causing BSI in the US decreased during 2010-2019. VanA remains the most common phenotype, whereas vanB-carrying isolates became rarer in later years. Interestingly, half of VanB-phenotype isolates carried a vanA gene. ORI was very active against EFM causing BSI, including isolates R to VAN, DAP, and/or nonsusceptible to LZD. Table 1 Disclosures Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals 1260. Activity of Manogepix (APX001A) against 2,669 Fungal Isolates from the SENTRY Surveillance Program (2018-2019) Stratified by Infection Type

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S646-S647
Author(s):  
Michael D Huband ◽  
Michael A Pfaller ◽  
Robert K Flamm ◽  
Shawn A Messer ◽  
Beth A Schaefer ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Infection Type ◽  
Chemical Diversity ◽  
Candida Spp ◽  
Services Research ◽  
Fungal Isolates ◽  
Infection Types ◽  
Center Research ◽  
Research Grant

Abstract Background Existing antifungal agents are active against many common fungal pathogens; however, breakthrough fungal infections occur and often involve less frequently encountered yeast and mould isolates. These rarer isolates tend to exhibit diminished susceptibility to current agents. Manogepix (MGX, APX001A) is a novel inhibitor of the fungal Gwt1 enzyme. The prodrug (fosmanogepix), is being evaluated in Phase 2 clinical trials for invasive candidiasis/candidemia, Candida auris infections, and invasive aspergillosis. In this study, we evaluated the in vitro activity of MGX and comparators against 2,669 clinical fungal isolates collected worldwide (2018-2019) and stratified by infection type. Methods Fungal isolates were collected from medical centers located in North America (34 sites; 42.3%), Europe (30 sites; 37.9%), Asia-Pacific (11 sites; 12.3%), and Latin America (7 sites; 7.6%). Isolates were collected from bloodstream infections (BSI; 51.7%), pneumonia in hospitalized patients (PIHP; 21.1%), skin and skin structure infections (SSSI; 5.5%), urinary tract infections (UTI; 2.3%), intraabdominal infections (IAI; 1.9%), and other infection types (17.5%). Results MGX demonstrated potent in vitro activity against 1,887 Candida spp. isolates from BSI, PIHP, SSSI, and all infection types (MIC50/90, 0.008/0.03-0.06 mg/L) outperforming all comparator agents (Table). Similarly, MGX was equally active against 578 Aspergillus spp. isolates (MEC50/90, 0.015/0.03 mg/L), regardless of infection type. MGX was active against Cryptococcus neoformans var. grubii isolates from BSI and ALL infection types with MIC50/90 values of 0.5/2 mg/L. Scedosporium spp. isolates from PIHP and all infection types were inhibited by low concentrations of MGX (MEC50/90, 0.03/0.03 mg/L). Table 1 Conclusion MGX demonstrated potent antifungal activity against Candida spp., Aspergillus spp., C. neoformans var. grubii, and non-Aspergillus moulds, including Scedosporium spp. isolates. Notable activity was seen against C. auris, echinocandin-resistant Candida spp., azole-resistant Aspergillus, and Scedosporium spp. isolates. Further clinical development of fosmanogepix in difficult-to-treat resistant fungal infections is warranted. Disclosures Michael A. Pfaller, MD, Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Shawn A. Messer, PhD, Amplyx Pharmaceuticals (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support) Beth A. Schaefer, n/a, Amplyx Pharmaceuticals (Research Grant or Support) Paul Bien, MS, Amplyx Pharmaceuticals (Employee) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

scholarly journals 166. Activity of a Novel β-lactamase Inhibitor QPX7728 Combined With β-lactams Against st258 klebsiella Pneumoniae and st131 escherchia Coli Isolates Producing β-lactamases

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S212-S213
Author(s):  
Mariana Castanheira ◽  
Jill Lindley ◽  
Timothy B Doyle ◽  
Andrew P Davis ◽  
Olga Lomovskaya
Keyword(s):  
Multidrug Resistant ◽  
Chemical Diversity ◽  
Sequencing Analysis ◽  
E Coli ◽  
Escherchia Coli ◽  
Global Spread ◽  
Encoding Genes ◽  
Center Research ◽  
Lactamase Inhibitor ◽  
Research Grant

Abstract Background ST258 K. pneumoniae and ST131 E. coli clones are considered vectors for the global spread of multidrug resistance. We evaluated the activity of β-lactams in combination with QPX7728, a novel β-lactamase inhibitor active against all β-lactamase classes, against a collection of 210 isolates belonging to these clones collected from a worldwide surveillance study. Methods A total of 118 ST258 K. pneumoniae and 92 ST131 E. coli (single loci variant also included) were susceptibility tested by reference broth microdilution against various β-lactams ± QPX7728 and comparator agents. All isolates were screened for β-lactamases using whole genome sequencing analysis. Results All β-lactam agents had limited activity against 118 ST258 K. pneumoniae (1.7–7.6% susceptible). Among these, 104 carried carbapenemase-encoding genes: 66 KPC variants, 20 NDM and 17 OXA-48-like. One isolate carried 2 carbapenemases. The addition of QPX7728 at 4 mg/L or 8 mg/L lowered the MICs for cefepime (MIC50/90, 0.25/1 mg/L and MIC50/90, 0.12/0.5 mg/L), ceftolozane (MIC50/90, 0.5/ > 32 mg/L and MIC50/90, 0.25/16 mg/L), ertapenem (MIC50/90, 0.12/2 mg/L and MIC50/90, 0.06/0.5 mg/L), and meropenem (MIC50/90, 0.06/0.5 mg/L and MIC50/90, 0.03/0.12 mg/L; Table). QPX7728 at 4 mg/L reduced the ceftibuten (MIC50/90, 0.25/8 mg/L) or tebipenem (MIC50/90, 0.12/2 mg/L) MICs for ST258 isolates. E. coli ST131 carried mainly CTX-M variant (85 isolates), but 6 isolates harbored carbapenemases. Carbapenems were the only β-lactams displaying > 80.0% activity against ST131 E. coli, followed by piperacillin-tazobactam (79.3% susceptible). Only 5.4%and 41.3% ST131 isolates were susceptible to cefepime and ceftibuten, respectively. MIC50/MIC90 values for these agents with QPX7728 were ≤ 0.015/≤ 0.015 mg/L for cefepime and ≤ 0.015/0.06 mg/L for ceftolozane with the inhibitor at 8 mg/L and ≤ 0.015/0.03 mg/L for ceftibuten with the inhibitor at 4 mg/L. Conclusion QPX7728 lowered the MICs for all agents tested to clinically achievable levels when tested against isolates multidrug resistant belonging to important clones responsible to the dissemination of KPC, CTX variants, and metallo-β-lactamases. The development of this broad β-lactamase inhibitor should be pursued. Table 1 Disclosures Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Jill Lindley, Allergan (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Olga Lomovskaya, PhD, Qpex Biopharma (Employee)

scholarly journals 1258. Activity of a Series of Investigational Compounds Tested Against Invasive Fungal Isolates

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S645-S646
Author(s):  
Paul R Rhomberg ◽  
Shawn A Messer ◽  
Richard W Scott ◽  
Simon D P Baugh ◽  
Michael A Pfaller ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Chemical Diversity ◽  
Candida Auris ◽  
Services Research ◽  
Defense Proteins ◽  
Fungal Isolates ◽  
Wide Range ◽  
Cryptococcus Spp ◽  
Center Research ◽  
Research Grant

Abstract Background Fox Chase Chemical Diversity Center (FCC) is developing non-peptide analogs of host defense proteins for the treatment of invasive fungal infections mainly caused by Candida (CAN) and Aspergillus (ASP). We evaluated the activity of 6 novel compounds and 2 comparators against 150 isolates from 15 fungal groups. Methods Susceptibility testing was performed per CLSI broth microdilution methods for investigational compounds and comparators against 70 CAN and 40 ASP isolates in addition to 10 Cryptococcus spp. (CRYP), 10 Fusarium spp. (FUS), 10 Mucorales, and 10 Scedosporium spp. (SCED) isolates from recent (2017-2019) clinical infections. MIC results were determined as ≥ 50% reduction at 24 and 72 hours for CAN and CRYP respectively, and 100% reduction at 24, 72, and 48 hours for Mucorales, SCED, and other moulds, respectively. CLSI clinical breakpoint (CBP) and epidemiological cutoff value (ECV) interpretive criteria were applied for comparators. Results Compounds FC10790, FC11083, FC11212, and FC11275 had MIC50 results at ≤ 0.015 mg/L and MIC90 results at ≤ 0.015 to 0.12 mg/L against CRYP, ASP, and FUS isolates. Compounds FC5096 and FC11022 were 2- to 4-fold less active while demonstrating MIC50 and MIC90 results of 0.03 to 0.5 mg/L against CAN, CRYP, ASP, and FUS isolates. The Mucorales isolate set showed the widest range of MIC results for FC compounds. FC10790 exhibited the greatest potency with a MIC50/90 at 0.5/2 mg/L. FC compounds showed potent activity against SCED with MIC90 results of 0.03 to 0.25 mg/L. Fluconazole showed a wide range of MIC results, from 0.06 to >64 mg/L, but the highest results observed were for Candida auris (MIC50/90, 64/ > 64 mg/L) and Candida krusei (MIC50/90; 16/32 mg/L). Itraconazole was active against all ASP (MIC50/90, 1/1 mg/L), but showed poor activity against FUS (MIC50/90, > 8/ > 8 mg/L). Amphotericin B showed a narrow range of MIC results (0.5 to 2 mg/L) for all isolates except 1 ASP and most SCED. Conclusion Novel FCC compounds showed equal or greater activity than comparators against most CAN, ASP, SCED, and FUS. FC10790, FC11212, and FC11275 showed the greatest activity against all tested fungal isolates. development of this series of compounds for clinical studies. Table 1 Disclosures Paul R. Rhomberg, n/a, Cidara Therapeutics (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Merck (Research Grant or Support) Shawn A. Messer, PhD, Amplyx Pharmaceuticals (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support) Richard W. Scott, PhD, Fox Chase Chemical Diversity Center (Employee) Simon DP Baugh, PhD, Fox Chase Chemical Diversity Center (Employee) Michael A. Pfaller, MD, Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals 327. Oritavancin Activity against Staphylococcus aureus Isolates Causing Bone and Joint Infections in European Hospitals (2010–2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S235-S236
Author(s):  
Cecilia G Carvalhaes ◽  
Jennifer M Streit ◽  
Helio S Sader ◽  
Rodrigo E Mendes
Keyword(s):  
Staphylococcus Aureus ◽  
Western Europe ◽  
Methicillin Resistance ◽  
Chemical Diversity ◽  
Surveillance Program ◽  
Services Research ◽  
Joint Infections ◽  
Bone And Joint Infections ◽  
Research Grant

Abstract Background Bone and joint infections (BJI) frequently are caused by Staphylococcus aureus (SA), and since prolonged therapy courses typically are required, agents with convenient administration are preferred. Oritavancin (ORI) is a long-acting lipoglycopeptide approved as a single dose regimen for treating skin and skin structure infections. This study evaluates the activity of ORI and comparators against SA causing BJI in European (EU) hospitals. Methods A total of 575 SA isolates from the SENTRY Antimicrobial Surveillance Program causing BJI in 15 EU countries from 2010 to 2019 were included. Bacterial identification was confirmed by MALDI-TOF MS. Broth microdilution susceptibility (S) testing and interpretation was performed following current CLSI guidelines. The activities of ORI and comparators were evaluated across the years and by EU region: western Europe (W-EU; 491 isolates) and eastern EU/Mediterranean region (E-EU; 84 isolates). Results Methicillin resistance (MRSA) was observed in 20.5% of SA (18.5% in W-EU and 32.1% in E-EU), ranging from 31.1% in 2011 to 14.6% in 2016. MRSA rates were slightly lower in 2016–2019 (14.6%-19.2%) than previous years (2011–2013; 24.4%-31.1%). ORI exhibited 100.0% susceptibility across the entire SA collection with yearly MIC50 and MIC90 variations within 1 doubling dilutions (MIC50 and MIC90, 0.015–0.03 and 0.03–0.06 mg/L, respectively), regardless the MRSA phenotype or EU region. Daptomycin, vancomycin, teicoplanin, and linezolid also showed complete coverage against SA. Clindamycin (CLI; >99.0%S) and levofloxacin (> 95.0%S) were active against methicillin-susceptible SA, but less active against MRSA (67.8%S and 16.1%S, respectively). E-EU MRSA isolates displayed lower S rates than W-EU MRSA isolates to ceftaroline (83.3% vs. 90.6%), CLI (44.4% vs. 74.7%) and tetracycline (66.7% vs. 89.0%), respectively. Conclusion MRSA rates among isolates causing BJI varied within regions. Although several drugs were in vitro active against MSSA, options remained limited against MRSA. ORI showed in vitro activity against the entire collection of European SA isolates and may be a consideration for treating BJI with the convenience of drug administration. Table 1 Disclosures Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals 37. Bloodstream Infections in the United States and Europe: Etiology and Antimicrobial Susceptibility Results from the SENTRY Antimicrobial Surveillance Program (2016–2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S20-S20
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Michael D Huband ◽  
Dee Shorttidge ◽  
Cecilia G Carvalhaes ◽  
...  
Keyword(s):  
Bloodstream Infections ◽  
The United States ◽  
Chemical Diversity ◽  
Surveillance Program ◽  
E Coli ◽  
Antimicrobial Surveillance ◽  
The Us ◽  
Resistance Rates ◽  
Center Research ◽  
Research Grant

Abstract Background The SENTRY Antimicrobial Surveillance Program monitored the etiology of bloodstream infections (BSI) and other infections worldwide since 1997. We evaluated the results for BSI in the United States (US) and Europe (EU). Methods Organisms were consecutively collected (1/patient) from 79 medical centers located in the US (n=12,748; 35 centers), western EU (W-EU; n=12,198; 29 centers from 10 nations: Belgium, France, Germany, Ireland, Italy, Portugal, Spain, Sweden, Switzerland, and the United Kingdom), and eastern EU (E-EU; n=3,297; 15 centers from 12 nations: Belarus, Croatia, Czech Republic, Greece, Hungary, Israel, Poland, Romania, Russia, Slovakia, Slovenia, and Turkey). Organisms were susceptibility tested by reference broth microdilution methods in a central laboratory. Results The most common organism found was S. aureus in the US and E. coli in W-EU and E-EU (Table). E. coli, S. aureus, and K. pneumoniae represented the top 3 organisms in all 3 regions and accounted for 53.9–54.8% of the collection. Gram-negative bacilli (GNB) represented 48.8% of organisms in the US, 59.8% in W-EU, and 65.6% in E-EU. MRSA rates were higher in US (41.6%) compared to W-EU (24.4%) and E-EU (24.6%). In contrast, susceptibility to ceftriaxone and levofloxacin among E. coli were lower in E-EU (66.4% and 55.8%, respectively) compared to W-EU (83.3% and 73.5%, respectively) and the US (83.0% and 65.8%, respectively). Among K. pneumoniae, susceptibility to ceftriaxone and meropenem were 86.6% and 98.7% in US, 64.3% and 84.7% in W-EU, and 30.2% and 72.5% in E-EU, respectively. CRE rates were lower in US (0.5%) compared to W-EU (2.8%) and very high in E-EU (10.4%). P. aeruginosa susceptibility to piperacillin-tazobactam and meropenem were 84.8% and 83.7% in US, 81.4% and 82.3% in W-EU, and 64.6% and 57.6% in E-EU, respectively. Vancomycin-nonsusceptibility (VRE) rates in the US, W-EU, E-EU were 3.2%, 0.9%, and 2.7% among E. faecalis, and 64.6%, 18.2%, and 30.6% among E. faecium, respectively. Table 1 Conclusion The frequency of GNB was lower in the US compared to W-EU and E-EU. Antimicrobial resistance rates among Gram-positive cocci were higher in the US compared to W-EU and E-EU; whereas, among GNB, resistance rates generally were higher in E-EU compared to W-EU and the US. Disclosures Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals 1253. In Vitro Activity of Omadacycline against 7000 Bacterial Pathogens from the United States Stratified by Infection Type (2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S644-S644
Author(s):  
Michael D Huband ◽  
Michael A Pfaller ◽  
Jennifer M Streit ◽  
Helio S Sader ◽  
Mariana Castanheira
Keyword(s):  
United States ◽  
The United States ◽  
Chemical Diversity ◽  
Vitro Activity ◽  
Multiple Infection ◽  
In Vitro Activity ◽  
Infection Types ◽  
Center Research ◽  
Research Grant

Abstract Background Omadacycline (OMC) is a new aminomethylcycline antibacterial drug belonging to the tetracycline class, for intravenous or oral administration. It is well tolerated and has proven effective in the treatment of a variety of bacterial infections. OMC is active against bacterial strains expressing the most common clinically relevant tetracycline resistance mechanisms, namely efflux and ribosomal protection. Methods 7,000 clinical isolates were collected during 2019 in the SENTRY Surveillance Program from 31 medical centers in the United States (US). Isolates were obtained from bloodstream infection (23.8%), skin and skin structure infection (21.6%), pneumonia in hospitalized patients (22.7%), urinary tract infection (14.5%), intraabdominal infection (6.2%), community acquired respiratory tract infection (10.3%) and other infection types (0.9%). Identifications were confirmed by MALDI-TOF. One isolate/patient/infection episode was tested. Broth microdilution susceptibility testing was conducted according to CLSI M07 (2018) and M100 (2020) guidelines. Results were interpreted using US FDA and CLSI breakpoint criteria. Results OMC demonstrated potent in vitro activity against Staphylococcus aureus isolates representing multiple infection types (MIC90, 0.12-0.25 mg/L; 94.7%-99.0% susceptible [S]) including MRSA (MIC90, 0.25 mg/L; 96.5% S) (Table). All S. lugdunensis (MIC90, 0.06 mg/L), Enterococcus faecalis (MIC90, 0.12-0.25 mg/L), and Haemophilus influenzae (MIC90, 1 mg/L) isolates were S to OMC. OMC was active against Streptococcus pyogenes isolates from SSSI (MIC90, 0.12 mg/L; 93.3%-98.5%S) including macrolide-resistant (R) strains. Similarly, S. pneumoniae isolates from RTI were S to OMC (MIC90, 0.06-0.12 mg/L; 98.8%-100%S) regardless of resistance to tetracycline or penicillin. Overall, 90.2%-93.6% of Enterobacter cloacae (MIC90, 4 mg/L) and 89.7%-94.7% of Klebsiella pneumoniae (MIC90, 4-8 mg/L) isolates from multiple infection types were S to OMC. Conclusion OMC demonstrated potent in vitro activity against Gram-positive and -negative bacterial pathogens from multiple infection types including SSSI and RTI and isolates displaying resistance to tetracycline, macrolides, and penicillin. Table 1 Disclosures Michael A. Pfaller, MD, Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

scholarly journals 1378. Evaluation of the In vitro Activity of Meropenem-Vaborbactam Against Carbapenem-Resistant Enterobacteriaceae, Including Isolates Resistant to Ceftazidime–Avibactam

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S422-S422
Author(s):  
William R Wilson ◽  
Ellen Kline ◽  
Chelsea Jones ◽  
Kristin Morder ◽  
Cornelius J Clancy ◽  
...  
Keyword(s):  
Premature Stop Codon ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Wild Type ◽  
In Vitro Susceptibility ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Research Grant

Abstract Background Meropenem-vaborbactam (M-V) is a novel antibiotic for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections. Our objective was to determine the in vitro activity of meropenem-vaborbactam against genetically-diverse CRE isolates, including those that have developed resistance to Ceftazidime–Avibactam (C-A). Methods Minimum inhibitory concentrations (MICs) were determined for meropenem (MER), M-V, and C-A by reference broth microdilution (BMD) methods in triplicate. Vaborbactam and avibactam were tested at fixed concentrations of 8 and 4 µg/mL, respectively. Quality control strains were used and within expected ranges. Polymerase chain reaction (PCR) with DNA sequencing was used to detect resistance determinants, including Klebsiella pneumoniae carbapenemase (KPC) subtypes and porin mutations. Results A total of 117 CRE isolates were tested, including K. pneumoniae (Kp; n = 83), E. cloacae (n = 17), E. coli (n = 10), and E. aerogenes (n = 7). Seventy-nine percent harbored blaKPC. KPC subtypes included KPC-2 (n = 32), KPC-3 (n = 41), KPC-3 variants (n = 16), and KPC [not typed] (n = 4, all E. coli). Among 74 K. pneumoniae, 95% had a premature stop codon in ompk35 and ompK36 genotypes included wild type (n = 48), IS5 insertion (n = 13), 135–136 DG duplication (n = 9), and other mutations (n = 4). The median (range) MICs for MER, C-A, and M-V were 8 (0.06 to ≥128), 1 (0.25 to ≥512), and 0.03 (0.015––16), respectively. Corresponding rates of susceptibility were 23, 84, and 98%, respectively. Fifty-three percent and 95% of C-A-resistant isolates were susceptible to MER and M-V, respectively. Among Kp, C-A MICs did not vary by KPC subtype or porin genotype. On the other hand, median M-V MICs were higher among KPC-2 than KPC-3 Kp (0.12 vs. 0.03; P = 0.002), and among Kp with ompK36 porin mutations compared with wild type (0.25 vs. 0.03; P < 0.001). Among Kp with KPC-3 variants (n = 16), the median M-V MIC was 0.03 (0.015––2); 100% were M-V susceptible. Median M-V MICs did not vary by CRE species. Only two isolates were M-V resistant, both were E. cloacae that did not harbor blaKPC. Conclusion M-V demonstrates high rates of in vitro susceptibility against diverse CRE isolates, including those that are resistant to C-A. As this agent is introduced into the clinic, it will be important to identify K. pneumoniae isolates harboring KPC-2 with ompK36 porin mutations that demonstrate higher MICs. Disclosures M. H. Nguyen, Merck: Grant Investigator, Research grant. Astellas: Grant Investigator, Research grant.

scholarly journals 1454. Plazomicin Activity against Enterobacterales Isolates Producing Extended-Spectrum β-Lactamases (ESBLs), Carbapenemases, and Aminoglycoside-Modifying Enzymes (AMEs) from United States (US) Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S729-S730
Author(s):  
Mariana Castanheira ◽  
Rodrigo E Mendes ◽  
Timothy B Doyle ◽  
Valerie Kantro ◽  
Helio S Sader ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Chemical Diversity ◽  
Services Research ◽  
Aminoglycoside Resistance ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Genes Encoding ◽  
Resistance Rates ◽  
Research Grant

Abstract Background Limited therapeutic options are available for the treatment of multidrug resistant (MDR) organisms. Plazomicin (PLZ) is an aminoglycoside developed to overcome common aminoglycoside-resistance mechanisms. We evaluated the activity of PLZ and comparators against Enterobacterales isolates collected in 2018-2019 carrying genes encoding ESBLs, carbapenemases, and AMEs. Methods Among 3,899 Enterobacterales isolates from US hospitals susceptibility (S) tested using reference broth microdilution method, 619 isolates from selected species displaying elevated MIC values for cephalosporins, carbapenems and/or resistance (CLSI criteria) to amikacin (AMK), gentamicin (GEN) and tobramycin (TOB) were submitted to whole genome sequencing for detection of resistance genes. Results Most isolates producing ESBLs (n= 418) carried blaCTX-M (n= 386). The activity of PLZ (99.3% susceptible [S]) was comparable to that of colistin and higher than other comparators against ESBL isolates (Figure). AMK inhibited 96.4% of the isolates and GEN and TOB inhibited 57.9% and 43.5%, respectively. Only 34 isolates produced carbapenemases, including 19 KPC-2, 10 KPC-3, 1 each with VIM-1, OXA-181, NDM-5 and KPC-2-like plus 1 isolate carrying the genes encoding NDM-1 and OXA-232. These isolates displayed higher resistance rates to comparators and only PLZ, and tigecycline inhibited >90% of these isolates. AMK and GEN inhibited 67.6% and 55.9% of these isolates, respectively. PLZ was active against 97.7% of isolates carrying AME genes (n= 306) that carried aac(6’)-Ib-cr (n =177), aac(3)-IIa (n = 159) and aac(3)-IId (n =81), among others. Most of these isolates were resistant to GEN and TOB (only 10.8-14.1% S), but 92.8% were S to AMK. Three K. pneumoniae isolates carried 16S rRNA methyltransferases, 1 armA (also harboring NDM-1) and 2 rmtB1. Conclusion The activity of PLZ against Enterobacteriaceae isolates carrying AMEs, ESBLs, and carbapenemases was greater than the activity of other aminoglycosides tested and comparable to those of tigecycline and colistin against carbapenemase-producing organisms. Isolates carrying genes encoding ESBLs, AMEs and carbapenemases are usually MDR and PLZ had activity against these organisms collected in the US. Figure 1 Disclosures Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Valerie Kantro, n/a, Cipla Ltd. (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Jaideep Gogtay, n/a, Cipla Ltd. (Employee) Sandhya Das, n/a, Cipla Ltd. (Research Grant or Support)

scholarly journals 1547. Activity of Tedizolid and Comparator Agents against Gram-Positive Bacterial Isolates Causing Skin and Skin Structure Infections in Pediatric Patients during 2015-2019 in the US

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S773-S773
Author(s):  
Cecilia G Carvalhaes ◽  
Helio S Sader ◽  
Paul R Rhomberg ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes
Keyword(s):  
Pediatric Patients ◽  
Chemical Diversity ◽  
Services Research ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Skin Structure ◽  
Broth Microdilution Method ◽  
The Us ◽  
Center Research ◽  
Research Grant

Abstract Background New strategies to treat acute bacterial skin and skin structure infections (ABSSSI) are needed due to the spread of methicillin-resistant Staphylococcus aureus (MRSA), a common multidrug resistant pathogen of ABSSSIs. Tedizolid (TZD) was approved by the US FDA for treating ABSSSI in adults and is under evaluation for treating pediatric patients. Accordingly, the activity of TZD and comparators was evaluated against clinical surveillance isolates collected from pediatric patients with SSSI in the US. Methods A total of 2,758 Gram-positive isolates were collected from pediatric patients with SSSIs in 33 sites in the US between 2015 and 2019 as part of the Surveillance of Tedizolid Activity and Resistance (STAR) Program. Bacterial identification was confirmed by MALDI-TOF MS and susceptibility (S) testing performed by the CLSI reference broth microdilution method. Current CLSI interpretative criteria was applied. Results S. aureus (SA; n=2,163; 78.4%) was the most frequent pathogen recovered from all age groups (≤ 1y; 2-5y; 6-12y; 13-17y), followed by β-hemolytic streptococci (BHS; n=460; 16.7%), and coagulase-negative staphylococci (CoNS; n=70; 2.5%). TZD was active against all SA (MIC50/90, 0.12/0.25 mg/L; 100% S). Equivalent TZD MIC50/90 values (0.12/0.25 mg/L) were observed against MRSA (n=886; 41.0%; MIC50/90, 0.12/0.25 mg/L) and methicillin susceptible (MSSA; MIC50/90, 0.12/0.25 mg/L) isolates, regardless the age group. TZD also was very active against BHS (MIC50/90, 0.12/0.25 mg/L; 100% S, regardless of species). TZD, linezolid, and daptomycin had 100.0% S rates against the main Gram-positive species and organism groups (Figure). Ceftaroline and clindamycin showed S rates of >90% against MRSA, MSSA, S. pyogenes and S. dysgalactiae. Lower S rates were observed for clindamycin against VGS (88.2%) and S. agalactiae (64.1%). TZD was the most potent agent (MIC90, 0.25 mg/L) against Enterococcus faecalis (n=30, 1.1%), and a vancomycin-resistance phenotype was observed in 1 (3.3%) isolate. Conclusion TZD was highly active against Gram-positive clinical isolates responsible for SSSI in pediatric patients across US hospitals from a 5-year period. TZD was equipotent or more potent than comparators against MSSA and MRSA isolates. Table 1 Disclosures Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Paul R. Rhomberg, n/a, Cidara Therapeutics (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Merck (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

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