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 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 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 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 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)

scholarly journals 1449. Frequency and Antimicrobial Susceptibility of Coagulase-Negative Staphylococcal (CoNS) Species Isolated from Clinical Specimens in United States and European Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S727-S727
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
Jennifer M Streit ◽  
S J Ryan Arends ◽  
Rodrigo E Mendes
Keyword(s):  
United States ◽  
Antimicrobial Susceptibility ◽  
Bloodstream Infections ◽  
The United States ◽  
Common Species ◽  
Chemical Diversity ◽  
Services Research ◽  
Clinically Significant ◽  
Research Grant

Abstract Background CoNS represent an important cause of bloodstream infections, osteoarticular infections, foreign-body-associated infections and endocarditis. We evaluated the frequency of CoNS species and the activity of dalbavancin (DALB) in comparison to vancomycin (VAN), daptomycin (DAP) and other agents against a large collection of CoNS isolates. Methods 5,088 CoNS isolates causing clinically significant infection were consecutively collected from 122 medical centers located in the United States (79 centers) and Europe (43 centers in 21 nations) over 6 years (2014-2019) and susceptibility tested by CLSI broth microdilution methods against DALB and comparators. Species identification was confirmed by MALDI-TOF. Results Most isolates were from bloodstream (BSI; 53.5%) or skin/skin structure infections (28.5%). S. epidermidis was the most common species overall (54.6%; Table) and for BSI (61.3%). The second most common species were S. lugdunensis overall (12.3%) and S. hominis for BSI (14.7%). DALB (MIC50/90, 0.03/0.06 mg/L) inhibited > 99.9% of CoNS isolates at the susceptible (S) breakpoint established by CLSI for S. aureus (≤ 0.25 mg/L) and was 8-fold more active than DAP (MIC50/90, 0.25/0.5 mg/L; 99.9% S) and 32-fold more active than VAN (MIC50/90, 1/2 mg/L; > 99.9% S). Linezolid was active against 98.7% of isolates (MIC50/90, 0.5/1 mg/L). All species were inhibited at ≤0.25 mg/L of DALB, except S. epidermidis (> 99.9%) and S. warneri (98.9%; Table). The most DALB-S species were S. capitis and S. simulans (MIC50/90, 0.015/0.03 mg/L for both species), whereas the highest DALB MIC50/90 values were observed with S. haemolyticus and S. saprophyticus (MIC50/90, 0.06/0.12 mg/L and highest MIC of 0.25 mg/L for both species). In contrast, 47.8% of S. epidermidis and 34.7% S. haemolyticus exhibited decreased susceptibility to VAN (MIC ≥ 2 mg/L), and 23.2% of S. capitis and 28.4% of S. warneri showed decreased susceptibility to DAP (MIC ≥ 1 mg/L). Overall oxacillin-S rate was 39.3%, varying from 3.0% for S. saprophyticus to 95.4% for S. lugdunensis. In general, BSI isolates were slightly less S than non-BSI isolates. Conclusion Antimicrobial susceptibility varied widely among CoNS species. DALB exhibited potent in vitro activity against all CoNS species. Table 1 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) S. J. Ryan Arends, PhD, Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (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 25. Update on Prevalence Of mcr-like Genes Among enterobacterales in a Global Surveillance Program: Decline in Occurrence of mcr-1.1 and Emergence of mcr-9.1 and mcr-10.1

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S13-S13
Author(s):  
Lalitagauri M Deshpande ◽  
Andrew P Davis ◽  
Rodrigo E Mendes ◽  
Mariana Castanheira
Keyword(s):  
Antimicrobial Agents ◽  
De Novo ◽  
Multidrug Resistant ◽  
Chemical Diversity ◽  
Surveillance Program ◽  
Services Research ◽  
Department Of Health ◽  
Antimicrobial Surveillance ◽  
Type Population ◽  
Research Grant

Abstract Background Increase in occurrence of infections caused by multidrug resistant organisms has prompted the usage of polymyxins and consequentially, resistance (R) to these antimicrobial peptides has risen. We have previously reported prevalence of mcr alleles from colistin (COL) non-susceptible (non-S) Enterobacterales (ENT) isolates from the SENTRY Antimicrobial Surveillance Program and in this study, we expand that knowledge by screening ENT isolates for this R mechanism collected during 2017 and 2018. Methods A total of 4,659 ENT isolates from 33 countries were S tested for COL and comparator antimicrobial agents by reference broth microdilution and sequenced using MiSeq as part of SENTRY Program. Most isolates were sequenced due to R to cephalosporins, carbapenems and/or aminoglycosides, but were not selected due to COL R. Sequences were de novo assembled and blasted against a local database for the mcr alleles: mcr-1.1 through mcr-10.1 and subtypes. Results COL R rate was 8.1% (MIC50/90, 0.12/0.5 mg/L) and mcr-like alleles were detected in 128 (2.8%) isolates. mcr-1.1 was present in 12 isolates (9.4%), 8 other mcr-variants were detected in 1 or 2 isolates each while majority of the isolates carried the newly described mcr-9.1 (92; 71.9%, 16 countries) or mcr-10.1 (16; 12.5%, Table). mcr-9.1 (73/92) and mcr-10.1 (15/16) were predominantly detected in Enterobacter cloacae. Isolates carrying mcr-9.1 showed COL MIC distributions similar to wild-type population (MIC50/90, 0.12/0.25 mg/L), while mcr-10.1 MIC distribution was higher (MIC50/90, 8/ > 8 mg/L). Conclusion A decline in the prevalence of mcr-1.1 was observed in this study period when compared to our prior studies. In contrast, mcr-9.1 and mcr-10.1 were observed in many isolates collected during 2017–18. Other mcr-variants were detected sporadically among ENT. Evaluating genetic context of these alleles to understand its dissemination and screening of COL non-S isolates for mcr is warranted. Table 1 Disclosures 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 1261. Antimicrobial Activity of Aztreonam-Avibactam against Gram-negative Bacteria Isolated from Patients Hospitalized with Pneumonia in Europe, Latin America, and Asia in 2019

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S647-S647
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Cecilia G Carvalhaes ◽  
Timothy B Doyle ◽  
Rodrigo E Mendes
Keyword(s):  
Latin America ◽  
Western Europe ◽  
Clinical Development ◽  
Chemical Diversity ◽  
Asia Pacific ◽  
Gram Negative Bacteria ◽  
Services Research ◽  
Gram Negative ◽  
Center Research ◽  
Research Grant

Abstract Background Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBL). Avibactam (AVI) is a non-β-lactam β-lactamase inhibitor that inhibits serine carbapenemases (CPEs), such as ESBLs, KPCs, AmpC, and some OXAs. ATM-AVI is under clinical development for treatment of serious infections caused by Gram-negative bacteria (GNB), including MBL-producers. Methods 2,582 GNB (1,630 Enterobacterales [ENT] and 952 nonfermentative-GNB) were consecutively collected (1/patient) from 56 medical centers located in Western Europe (W-EU; 22 centers in 10 nations), Eastern Europe (E-EU; 12 centers in 9 nations), Latin America (LATAM; 10 centers 6 nations), and the Asia-Pacific region (APAC; 12 centers in 8 nations) in 2019 and susceptibility (S) tested against ATM-AVI and comparators at a central laboratory by reference broth microdilution methods. Results Overall, 99.9% of ENT (MIC50/90, 0.06/0.25 mg/L), including 99.1% of carbapenem-resistant ENT (CRE; MIC50/90, 0.25/0.5 mg/L), were inhibited at an ATM-AVI MIC of ≤ 8 mg/L (Table). CRE rates were 1.4%, 23.7%, 6.3%, and 9.6% in W-EU, E-EU, LATAM, and APAC, respectively (6.9% overall). A CPE was identified in 95 of 113 CRE isolates (84.1%). These CPEs included NDM-like (31.0% of CRE), KPC-like (26.5%), OXA-48-like (24.8%), and VIM-like (7.1%). Six isolates produced 2 CPEs. The highest ATM-AVI MIC value among MBL-producers (n=43; MIC50/90, 0.12/0.5 mg/L) was 4 mg/L. Among P. aeruginosa, 75.1% were inhibited at ≤ 8 mg/L of ATM-AVI; S to meropenem (MEM), piperacillin-tazobactam, and ceftazidime were 69.4%, 72.5%, and 75.7%, respectively, and ranged from 64.3% in E-EU to 82.0% in W-EU. MEM non-S P. aeruginosa varied from 22.2% in W-EU to 54.8% in E-EU. ATM-AVI was highly active against S. maltophilia, inhibiting 95.0%, 100.0%, 100.0%, and 90.0% of isolates from W-EU, E-EU, LATAM, and APAC, respectively, at ≤8 mg/L. S. maltophilia S to cotrimoxazole were 90.0%, 97.7%, 85.7%, and 100.0% in W-EU, E-EU, LATAM, and APAC, respectively. ATM-AVI also was very active against Burkholderia spp. (highest MIC, 8 mg/L). Conclusion Our results support clinical development of ATM-AVI to treat pneumonia caused by ENT (including MBL-producers), P. aeruginosa, S. maltophilia, and Burkholderia spp. Table 1 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) 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) 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 1148. Activity of Posaconazole and Comparator Antifungal agents Tested Against Filamentous Fungi

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S601-S601
Author(s):  
Mariana Castanheira ◽  
Cecilia G Carvalhaes ◽  
Mary Motyl ◽  
Seongah Han ◽  
Havilland Campbell
Keyword(s):  
Amphotericin B ◽  
Filamentous Fungi ◽  
Antifungal Agents ◽  
Chemical Diversity ◽  
Aspergillus Species ◽  
Asia Pacific ◽  
Broth Microdilution Method ◽  
Center Research ◽  
Scedosporium Species ◽  
Research Grant

Abstract Background Posaconazole (POS) is a broad-spectrum triazole antifungal that exhibits potent antifungal activity against a variety of yeasts and molds. We evaluated the in vitro activities of posaconazole and comparator antifungal agents against 2,554 isolates of filamentous fungi including 2,100 Aspergillus species and 454 non-Aspergillus moulds (98 Fusarium, 81 Mucorales and 76 Scedosporium species isolates) collected worldwide in 2010-2018 from clinically significant infections. Methods Isolates were identified using sequencing and/or MALDI-TOF MS methods. Posaconazole, itraconazole, voriconazole, caspofungin, anidulafungin, micafungin, and amphotericin B were tested using the reference broth microdilution method according to CLSI guidelines. Results Posaconazole showed comparable activity to itraconazole and voriconazole against A. fumigatus. Categorical agreement between posaconazole and the other azoles tested against A. fumigatus ranged from 98.2-98.7%. Most of the Aspergillus species isolates tested (>90%) were WT to all azoles and echinocandins. Among the isolates of A. fumigatus, the rate of NWT strains varied across the different geographic regions. The frequency of azole NWT strains of A. fumigatus from Europe increased steadily from 2010 to 2018. There was no consistent trend for an increased frequency of NWT strains from other geographic areas. The azoles and echinocandins showed poor activity against Fusarium and Scedosporium species. Posaconazole (MIC50/90, 1/2 mg/L) and amphotericin B (MIC50/90, 1/2 mg/L) were the most active agents against the Mucorales isolates. Conclusion Posaconazole exhibited excellent activity against most species of Aspergillus and was comparable to itraconazole and voriconazole. Most Aspergillus species remain susceptible to triazoles. Although there was no evidence for an increasing frequency of NWT strains among A. fumigatus isolates from North America, Latin America or the Asia-Pacific region, we confirm an increase in the rate of NWT strains to all three triazoles among isolates from Europe. 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) 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) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Seongah Han, PhD, Merck & Co, Inc. (Employee) Havilland Campbell, BS, Merck & Co, Inc. (Employee)

scholarly journals 1590. Activity of Meropenem-Vaborbactam and Single-Agent Comparators against Enterobacterales Isolates Including KPC-Producing Isolates, from European Patients Hospitalized with Pneumonia Including Ventilator-Associated Pneumonia (2014-2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S792-S792
Author(s):  
Dee Shorttidge ◽  
Lalitagauri M Deshpande ◽  
Leonard R Duncan ◽  
Jennifer M Streit ◽  
Mariana Castanheira
Keyword(s):  
Single Agent ◽  
Chemical Diversity ◽  
Ventilator Associated Pneumonia ◽  
Services Research ◽  
Icu Patients ◽  
Active Comparator ◽  
Extended Spectrum Beta Lactamase ◽  
Abdominal Infections ◽  
Hospital Acquired ◽  
Research Grant

Abstract Background Meropenem-vaborbactam (MVB) was recently approved in Europe for the treatment of complicated UTIs, including acute pyelonephritis, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP), and bacteremia. KPC-producing Enterobacterales (ENT) isolates have disseminated worldwide. We analysed the activity of MVB and single-agent comparators against 6,846 ENT isolates from patients hospitalised with pneumonia (PHP) including VAP in European hospitals (2014–2019). Methods Among 6,846 ENT clinical isolates from PHP collected in 40 European hospitals located in 20 countries that were susceptibility (S) tested using reference broth microdilution methods. Of the carbapenem-resistant isolates submitted to whole genome sequencing, 75 carried blaKPC. ENT isolates were also characterized for an extended spectrum beta-lactamase (ESBL) phenotype as described (CLSI, 2020). EUCAST (2020) interpretive criteria were used. %S from patients in the intensive care unit (ICU), ICU patients with VAP, and non-ICU isolates were also analysed. Results The most common ENT pathogens isolated from PHP were Klebsiella pneumoniae (KPN; n=1,877) and Escherichia coli (EC; n=1,646). The %S of MVB and comparators to ENT, ICU, ICU/VAP, and non-ICU are shown in the table. Overall, 98.2% of ENT were S to MVB. For 3,218 ENT isolates from ICU patients, MVB %S was 96.6% and for 2,627 non-ICU isolates MVB %S was 98.5%. The %S of comparators for ICU vs non-ICU isolates were similar, except for levofloxacin. 29 KPC-producing isolates were from ICU (11 from VAP), 46 were from non-ICU. Most KPC-producing isolates were KPN (n=71; 54 blaKPC-3, 16 blaKPC-2 and 1 blaKPC-12). 4 EC contained blaKPC-3. KPC were from 7 countries, Italy had the highest number of KPC-producing isolates at 42 (56%). MVB inhibited 100% of KPC-producing isolates. Amikacin was the most active comparator against all ENT (94.2%S); colistin was the most active comparator against KPC-producing isolates (79.7%S). Conclusion These results demonstrate MVB has potent activity against ENT isolates from PHP including those producing KPC enzymes and suggest MVB is a useful treatment option for ICU and non-ICU PHP including VAP. Table 1 Disclosures Leonard R. Duncan, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Dept of Health and Human Services (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)

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