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 Antimicrobial Activity of High-Proportion Cefepime-Tazobactam (WCK 4282) against a Large Number of Gram-Negative Isolates Collected Worldwide in 2014

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Bloodstream Infections ◽  
The United States ◽  
Clinical Development ◽  
Surveillance Program ◽  
Content Type ◽  
E Coli ◽  
Highly Active ◽  
Microdilution Method ◽  
Antimicrobial Surveillance ◽  
Broth Microdilution Method

ABSTRACT Cefepime-tazobactam (WCK 4282) is currently under clinical development for use at a dosage of 2 g/2 g every 8 h. A total of 7,981 isolates were collected from 146 medical centers (39 countries) in 2014 as a part of the SENTRY Antimicrobial Surveillance Program, and their susceptibilities to cefepime-tazobactam (with tazobactam at fixed concentrations of 4 and 8 μg/ml) were tested by a reference broth microdilution method. Isolates were mainly from patients with pneumonia (29.5%) and bloodstream infections (26.9%). Cefepime-tazobactam (with tazobactam at a fixed concentration of 8 μg/ml) and cefepime inhibited 96.9 and 87.9% of Enterobacteriaceae strains at ≤8 μg/ml. The activity of cefepime-tazobactam against Enterobacteriaceae strains was comparable to that of meropenem (96.7% of isolates were susceptible) and greater than that of piperacillin-tazobactam (87.7% susceptible). All Enterobacteriaceae species from the United States except Klebsiella pneumoniae had >99.0% of isolates inhibited by cefepime-tazobactam at ≤8/8 μg/ml. The prevalence of the extended-spectrum β-lactamase (ESBL)-screening-positive phenotype was the highest among Escherichia coli isolates in China (66.3%) and among K. pneumoniae isolates (58.0%) in Latin America. Cefepime-tazobactam at ≤8/8 μg/ml inhibited 98.7 and 71.3% of ESBL-screening-positive phenotype E. coli strains and K. pneumoniae strains, respectively. Meropenem showed limited activity against ESBL-screening-positive phenotype K. pneumoniae strains (69.6% susceptible). Cefepime-tazobactam was active against Enterobacter spp. (MIC50 and MIC90, 0.06 and 0.5 μg/ml, respectively), including ceftazidime-nonsusceptible isolates (96.1% of isolates were inhibited by cefepime-tazobactam at ≤8/8 μg/ml). The activity of cefepime-tazobactam against Pseudomonas aeruginosa (82.4 and 91.6% of isolates were inhibited by cefepime-tazobactam at ≤8/8 and ≤16/8 μg/ml, respectively) was comparable to that of meropenem and piperacillin-tazobactam (79.2% susceptible). In summary, cefepime-tazobactam was highly active against P. aeruginosa and Enterobacteriaceae strains, including ESBL-screening-positive phenotype E. coli strains and ceftazidime-nonsusceptible Enterobacter spp. These results support the further clinical development of the cefepime-tazobactam combination.

scholarly journals 1472. Frequency of Occurrence and Antimicrobial Susceptibility of Bacteria Isolated from Patients Hospitalized with Bacterial Pneumonia in the United States, Western Europe, and Eastern Europe: Results from the SENTRY Program (2016-2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S737-S738
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Dee Shorttidge ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Bacterial Pneumonia ◽  
Western Europe ◽  
Rank Order ◽  
The United States ◽  
Chemical Diversity ◽  
Frequency Of Occurrence ◽  
The Us ◽  
Center Research ◽  
Research Grant

Abstract Background The SENTRY Antimicrobial Surveillance Program monitors the frequency of occurrence and antimicrobial susceptibility of organisms from various infection types worldwide. In this investigation, we evaluate the results for organisms isolated from patients hospitalized with bacterial pneumonia. Methods 28,918 bacterial isolates were consecutively collected (1/patient) in 2016-2019 from 121 medical centers located in the United States (US; n=17,770; 82 centers), western Europe (W-EU; n=7,966; 25 centers from 10 nations), and eastern Europe (E-EU; n=3,182; 14 centers from 11 nations). Organisms were tested for susceptibility by reference broth microdilution methods in a central laboratory. Results The rank order of organisms varied markedly among geographic regions (Table). Gram-negative bacilli (GNB) represented 69.1%, 76.3%, and 88.6% of organisms; and non-fermentative (NF) GNB represented 34.6%, 26.9%, and 51.8% of organisms in US, W-EU, and E-EU, respectively. Among NF-GNB, P. aeruginosa ranked first in W-EU and E-EU and second in the US, A. baumannii ranked third in E-EU, and S. maltophilia was among the top 8 in all 3 regions (fifth in the US). P. aeruginosa susceptibility to piperacillin-tazobactam and meropenem (MEM) were 76.1% and 74.8% in the US, 75.4% and 76.9% in W-EU, and 57.4% and 48.3% in E-EU, respectively. Only 10.4% of A. baumannii isolates from E-EU were MEM-susceptible compared to 45.8% in W-EU and 58.7% in the US. MRSA rates in the US improved from 44.8% in 2016 to 40.2% in 2019 (p< 0.05). Overall MRSA rates were 21.4% in W-EU, and 28.7% in E-EU. CRE rates decreased continuously in the US from 3.0% in 2016 to 1.7% in 2019 (p < 0.05; 2.4% overall) and were higher E=EU (16.6%) than W-EU (2.2%). Among K. pneumoniae, susceptibility to ceftriaxone and MEM were 80.7% and 94.9% in the US, 70.1% and 90.7% in W-EU, and 34.5% and 70.4% in E-EU, respectively. Among E. coli, susceptibility to ceftriaxone and levofloxacin were 71.4% and 55.0% in the US, 79.2% and 71.2% in W-EU, and 62.6% and 55.9% in E-EU, respectively. Table 1 Conclusion Rank order and antimicrobial susceptibility of bacteria isolated from patients with pneumonia varied widely by geographic region. Multidrug-resistant NF-GNB represented an important cause of pneumonia in US and Europe. 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) 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) 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) 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 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 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 1226. In Vitro Activity of Tebipenem and Comparators Against Enterobacterales Collected from Patients with Bloodstream Infections as Part of the 2019 Global STEWARD Surveillance Program

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S702-S702
Author(s):  
Ian A Critchley ◽  
Nicole Cotroneo ◽  
Rodrigo E Mendes ◽  
Michael J Pucci
Keyword(s):  
Bloodstream Infections ◽  
Clinical Development ◽  
Asia Pacific ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Medical Centers ◽  
Oral Agents ◽  
The Us ◽  
Research Grant

Abstract Background Bloodstream infections (BSI) are a significant cause of morbidity and mortality. Enterobacterales (ENT) are frequently implicated in BSI with an increase in organisms producing extended-spectrum β-lactamase (ESBL). This challenges a possible transition to current oral agents due to co-resistance. Carbapenems are active against ESBL-ENT and tebipenem (TBP) is a new oral carbapenem in clinical development. The aim of the study was to assess resistance (R) among BSI isolates and activity of TBP and comparators against ENT collected in a 2019 surveillance study. Methods 2612 ENT from BSI were centrally tested by reference broth microdilution. Isolates were from medical centers in the US, Europe (EU), Latin America (LA) and Asia Pacific (AP). MIC results were interpreted according to CLSI, including ESBL assignment. CRE were sequenced to identify carbapenemase genes. Results Among the ENT, non-susceptibility (NS) rates to ceftazidime, levofloxacin were 20.4 and 27.0%, respectively, and R to trimethoprim-sulfamethoxazole was 31.1%. NS rates for ertapenem (ETP) and MER were 4.9 and 2.7%, respectively. MIC90s for TBP, ETP and MER were 0.12, 0.12 and 0.06 µg/mL, respectively. The MIC90 for TBP was 0.06 µg/mL for ENT from the US and 0.12 µg/mL for isolates from EU, LA and AP. Escherichia coli (EC) was the most prevalent (52% of ENT isolates) and the MIC90 for TBP ranged from 0.015 µg/mL for isolates in the US/EU to 0.03 µg/mL for isolates in LA/AP. ESBL-EC ranged from 15.7% in US to 34.3% in LA. TBP was active against ESBL-EC with an MIC90 of 0.03 µg/mL. Klebsiella pneumoniae (KP) accounted for 22.7% of BSI caused by ENT and TBP MIC90 ranged from 0.06 µg/mL for KP in US to >8 µg/mL in EU, LA and AP. MER-R KP ranged from 2.4% in US to 14.9% in LA. KPC-2, -3 and NDM were the most prevalent carbapenemases. TBP MIC90 values for MER-S ESBL KP in EU, LA and AP were ≤0.12 µg/mL. Conclusion TBP activity was similar to ETP and MER against ENT responsible for BSI. R to oral agents was compromised by ESBL co-resistance. TBP was among the most active agents against EC isolates and ESBL phenotypes. Among KP, TBP was more active against isolates from US where prevalence of CRE was lower than EU, LA and AP. TBP may be considered as an alternative oral option for BSI caused by non-CRE ESBL-producing ENT. Disclosures Ian A. Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) 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)

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 Ceftobiprole Activity When Tested Against Contemporary Bacteria Causing Bloodstream Infections in the US (2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S368-S368 ◽  
Author(s):  
Robert K Flamm ◽  
Leonard R Duncan ◽  
Dee Shortridge ◽  
Jennifer I Smart ◽  
Kamal Hamed ◽  
...  
Keyword(s):  
Bloodstream Infections ◽  
Community Acquired Pneumonia ◽  
Surveillance Program ◽  
Coagulase Negative Staphylococci ◽  
Two Phase ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
The Us ◽  
Research Grant

Abstract Background Ceftobiprole medocaril (prodrug of ceftobiprole) is an advanced cephalosporin, approved for adults in multiple European countries for the treatment of hospital-acquired pneumonia (excluding ventilator-associated pneumonia) or community-acquired pneumonia. It is not approved in the US; however, it has achieved qualified infectious disease product status and two phase 3 studies supported by BARDA are planned to begin in the US in 2017. Methods A total of 2,787 Gram-positive (GP) and -negative (GN) isolates from bloodstream infections (BSI) from 30 medical centers in the SENTRY Antimicrobial Surveillance Program were evaluated. Isolates were collected in the US during 2016. Susceptibility (S) testing was performed by reference broth microdilution method against ceftobiprole and comparators. Isolates included 693 Staphylococcus aureus (SA), 216 coagulase-negative staphylococci (CoNS), 244 enterococci, 63 Streptococcus pneumoniae (SPN), 74 viridans group streptococci (VGS), 138 β-haemolytic streptococci (BHS), 1,105 Enterobacteriaceae (ENT), 129 Pseudomonas aeruginosa (PSA), 41 Acinetobacter spp. (ASP), 30 Stenotrophomonas maltophila, 19 Haemophilus spp. and 35 miscellaneous bacteria. Results Methicillin-resistant S. aureus (MRSA) S rates were lower than for methicillin-susceptible S. aureus (MSSA) for most agents. For levofloxacin (LEV) and erythromycin (ERY), the S rates were LEV: MRSA, 23.2%; MSSA, 86.1%; ERY: MRSA, 9.0%; MSSA, 69.3%. All MSSA and 99.0% of MRSA were S to ceftobiprole, while all MSSA and 96.5% of MRSA were S to ceftaroline (CPT). For CoNS, 98.1% of ceftobiprole MIC values were ≤2mg/L. Ceftobiprole was active against Enterococcus faecalis (96.1% ≤2mg/L) and not against E. faecium (18.9% ≤2mg/L). Against ENT, ceftobiprole (85.0%S) was similar in activity to ceftazidime (CAZ, 87.2%S) and cefepime (FEP, 88.9%S). The MIC50/90 values for ceftobiprole, FEP, and CAZ against PSA were identical at 2/16 mg/L. Conclusion Ceftobiprole exhibited potent in vitro activity against GP and GN isolates from contemporary BSI in the US. These results support further clinical evaluation of ceftobiprole for the treatment of BSI. Disclosures R. K. Flamm, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; L. R. Duncan, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; D. Shortridge, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; J. I. Smart, Basilea Pharmaceutica International Ltd.: Employee, Salary; K. Hamed, Basilea Pharmaceutica International Ltd.: Employee, Salary; R. E. Mendes, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; H. S. Sader, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant

scholarly journals 1589. Activity of Meropenem-Vaborbactam and Comparators against Globally Disseminated Klebsiella pneumoniae Sequence Type 258

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S791-S792
Author(s):  
Dee Shorttidge ◽  
Lalitagauri M Deshpande ◽  
Timothy B Doyle ◽  
Jennifer M Streit ◽  
Mariana Castanheira
Keyword(s):  
Klebsiella Pneumoniae ◽  
Active Agent ◽  
Sequence Type ◽  
Chemical Diversity ◽  
Surveillance Program ◽  
Drug Classes ◽  
The Us ◽  
Abdominal Infections ◽  
Hospital Acquired ◽  
Research Grant

Abstract Background Meropenem-vaborbactam (MVB) is a combination of a carbapenem and a b-lactamase inhibitor active against β-lactamases including serine carbapenemases. MVB recently was approved in the US and Europe for the treatment of complicated UTIs, including acute pyelonephritis, and is approved in Europe for treatment of complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, ventilator-associated pneumonia, and bacteremia. Carbapenemase-producing Enterobacterales (ENT) isolates, particularly Klebsiella pneumoniae (KPN), have disseminated worldwide and are considered endemic in various countries. Carbapenem-resistant (CR) KPN outbreaks have been associated with KPN sequence-type 258 (ST258). Globally, 60-70% of KPC-producing KPN belong to ST258. In this study, we examined the susceptibilities of ST258 isolates collected as a part of the SENTRY global surveillance program. Methods KPN isolates from 2016-2019 were susceptibility tested by reference broth microdilution methods. The results were interpreted using CLSI 2020 breakpoints. The sequence type and presence of carbapenemases were determined by whole genome sequencing and analysis. Results 130 KPN ST258 isolates were identified in 6 countries. All isolates were extremely drug resistant (XDR, susceptible to < = 1 agent in 2 or fewer drug classes). 76.2% were CR, and 71 isolates contained blaKPC-2, 25 blaKPC-3 and 1 blaKPC-12. One isolate contained blaNDM-1. The US had the most ST258 isolates (n=56), of which 22 produced KPC-2 and 19 produced KPC-3. Greece had 32 isolates, with 17 KPC-2 and 5 KPC-3. Brazil had 22 isolates, 17 with KPC-2. The single NDM-1 producing isolate was from Argentina. Susceptibilities to MVB and comparators by country are shown in the table. MVB inhibited 99.2% of the isolates and was the most active agent overall, only 23.1% were meropenem susceptible. Tigecycline was the most active comparator with 98.5% susceptible. Conclusion These results demonstrate MVB has potent activity against the internationally disseminated KPN clone ST258 including those producing KPC. MVB may be useful for the treatment of infections caused by XDR K. pneumoniae. Table 1 Disclosures 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) 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)

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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