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 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 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 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)

Aztreonam/avibactam activity against clinical isolates of Enterobacterales collected in Europe, Asia and Latin America in 2019

2020 ◽  
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
S J Ryan Arends ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes
Keyword(s):  
Latin America ◽  
Western Europe ◽  
Multidrug Resistant ◽  
Clinical Development ◽  
Asia Pacific ◽  
Asia Pacific Region ◽  
Carbapenem Resistant ◽  
Serious Infections ◽  
Susceptibility Tests

Abstract Background Aztreonam is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs) and avibactam is a non-β-lactam β-lactamase inhibitor that effectively inhibits serine carbapenemases (CPs). Aztreonam/avibactam is under clinical development for treatment of serious infections caused by Gram-negative bacteria, including MBL-producers. Objectives To evaluate the in vitro activity of aztreonam/avibactam against clinical Enterobacterales isolates. Methods 8787 Enterobacterales were collected consecutively from 64 medical centres located in Western Europe (W-EU; n = 4616; 26 centres in 10 nations), Eastern Europe (E-EU; n = 1554; 11 centres in 9 nations), the Asia-Pacific region (APAC; n = 1456; 17 centres in 9 nations), and Latin America (LATAM; n = 1161; 10 centres in 6 nations). Susceptibility tests were performed by reference broth microdilution methods and interpreted according to EUCAST criteria. Results 99.9% of isolates were inhibited at aztreonam/avibactam MIC of ≤8 mg/L (MIC50/90, ≤0.03/0.12 mg/L), including 99.7% of carbapenem-resistant (CRE; n = 396; MIC50/90, 0.25/0.5 mg/L) and 99.7% of multidrug-resistant isolates (n = 1706; MIC50/90, 0.06/0.5 mg/L). CRE rates were 1.2%, 12.9%, 5.2%, and 5.8% in W-EU, E-EU, APAC, and LATAM, respectively (4.5% overall). A CP was identified in 90.2% of CRE isolates. The most common CPs were variants of KPC (35.9% of CRE), NDM (29.0%), and OXA-48 (26.8%). The highest aztreonam/avibactam MIC value among MBL-producers (n = 110; MIC50/90, 0.12/0.5 mg/L) was 2 mg/L. Susceptibility rates for ceftriaxone, meropenem, levofloxacin, and amikacin were highest in W-EU (80.9%, 99.0%, 80.7% and 97.9%, respectively) and lowest in E-EU (52.0%, 88.9%, 54.1%, and 84.2%, respectively). Conclusions Our results support clinical development of aztreonam/avibactam to treat infections caused by Enterobacterales, including MBL-producers.

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

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

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

scholarly journals 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 1278. Impact of Different Breakpoint Criteria on the Susceptibility Rates of Enterobacterales resistant Subsets to the Aminoglycosides

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S654-S655
Author(s):  
Helio S Sader ◽  
S J Ryan Arends ◽  
Jaideep Gogtay ◽  
Cecilia G Carvalhaes ◽  
Mariana Castanheira
Keyword(s):  
The United States ◽  
Multidrug Resistant ◽  
Chemical Diversity ◽  
Asia Pacific ◽  
Medical Centers ◽  
Carbapenem Resistant ◽  
Us Fda ◽  
Tract Infections ◽  
Center Research ◽  
Research Grant

Abstract Background Plazomicin (PLZ) is an aminoglycoside recently approved by the United States (US) Food and Drug Administration (FDA) for the treatment of complicated urinary tract infections, including pyelonephritis. We evaluated the susceptibility (S) rates of PLZ, amikacin (AMK), gentamicin (GEN) and tobramycin (TOB) by applying current breakpoints published by different organizations. Methods A total of 9,303 Enterobacterales (ENT) isolates (1/patient) were collected in 2018-2019 from medical centers located in the US (n=3,899; 33 centers), Europe (n=3,782; 39 centers in 19 nations), Asia-Pacific (n=795; 13 centers in 7 nations [2018 only]), and Latin America (n=827; 10 centers in 6 nations [2018 only]). PLZ and comparator agents were S tested by reference broth microdilution methods at a central laboratory. Breakpoints for the following organizations were applied when available: CLSI, EUCAST, USCAST, and US FDA. Results PLZ was active against 95.5% and 98.0% of isolates as per US FDA (≤2 mg/L) and USCAST (≤4 mg/L) criteria, respectively. S rates as per US FDA and USCAST criteria were 97.4% and 90.2% for AMK, 86.4% and 85.6% for GEN, and 83.8% and 81.1% for TOB, respectively (Table). CLSI and US FDA breakpoints were identical for these three older aminoglycosides, and EUCAST breakpoints were identical for GEN and TOB and one doubling dilution higher for AMK when compared with USCAST. Per US FDA criteria, carbapenem-resistant ENT (CRE) S rates to PLZ and AMK were 71.5% and 58.3%, respectively. Differences in S rates between PLZ and AMK were higher when applying USCAST for resistant subsets, such as CRE (72.2% versus 38.5%, respectively), ESBL-phenotype (92.7% versus 72.4%, respectively), and multidrug-resistant isolates (n=1,348; 88.6% versus 59.6%, respectively). GEN and TOB exhibited limited activity against ENT resistant subsets. Conclusion PLZ retained potent activity against ENT, including resistant subsets. The discrepancies among the S rates for aminoglycosides were greater when applying breakpoints generated using the same stringent contemporary methods applied to determine PLZ breakpoints. 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) 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) Jaideep Gogtay, n/a, Cipla Ltd. (Employee) 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) 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 1620. Minocycline Activity Against Unusual Clinically Significant Gram-Negative Pathogens

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S802-S803
Author(s):  
Dee Shorttidge ◽  
S J Ryan Arends ◽  
Jennifer M Streit ◽  
Mariana Castanheira ◽  
Robert K Flamm
Keyword(s):  
Burkholderia Cepacia ◽  
Species Complex ◽  
Resistance Mechanisms ◽  
Chemical Diversity ◽  
Achromobacter Xylosoxidans ◽  
Surveillance Program ◽  
Services Research ◽  
Gram Negative ◽  
Broth Microdilution Method ◽  
Research Grant

Abstract Background Unusual non-glucose fermenting Gram-negative (NFGN) pathogens, including Burkholderia cepacia species complex, Achromobacter spp, Alcaligenes spp, Aeromonas spp, and other genera, can cause serious hospital-acquired infections in immunocompromised patients. Some genera are inherently resistant to common drug classes and can acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the susceptibility of NFGN isolates to minocycline (MIN). Isolates were collected as part of the SENTRY Antimicrobial Surveillance Program from 2014-2019. Methods From 2014-2019, unusual NFGN isolates were collected from hospitalized patients in 102 hospitals in 35 countries on 4 continents. Hospitals submitted 1 isolate per patient per infection episode that met local criteria for being the likely causative pathogen. Identification was performed by the submitting laboratory and confirmed by JMI Laboratories with matrix-assisted laser desorption ionization-time of flight mass spectrometry or other molecular methods as required. Isolates were tested for MIN susceptibility using the CLSI broth microdilution method at JMI Laboratories. All infection types were included in the susceptibility analysis. Results The most common infection from which the NFGN were isolated was pneumonia. The top 5 NFGN species were Achromobacter xylosoxidans (n=202), Burkholderia cepacia species complex (n=199), unspeciated Achromobacter (n=190), Aeromonas spp (n=127), including Aeromonas hydrophila (n=35), Chryseobacterium spp (n=59), and Alcaligenes faecalis (n=42). The % susceptible and MIC50/90 values of MIN for these species are shown in the table. Conclusion MIN had > 85% susceptible for the most frequently isolated unusual NFGN, including 92% susceptible for Achromobacter spp. and 85.9% for B. cepacia. These data suggest that MIN remains a useful treatment option for infections caused by unusual NFGN. Activities of MIN when tested against NFGN isolates Disclosures 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) 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) 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)

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)

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