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

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)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1624 ◽

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)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1809 ◽

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)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.523 ◽

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)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa417.036 ◽

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)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1635 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S729-S730

Author(s):

Mariana Castanheira ◽

Rodrigo E Mendes ◽

Timothy B Doyle ◽

Valerie Kantro ◽

Helio S Sader ◽

...

Keyword(s):

Multidrug Resistant ◽

Resistance Mechanisms ◽

Chemical Diversity ◽

Services Research ◽

Aminoglycoside Resistance ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Genes Encoding ◽

Resistance Rates ◽

Research Grant

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

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1620. Minocycline Activity Against Unusual Clinically Significant Gram-Negative Pathogens

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1800 ◽

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)

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Antimicrobial Activities of Tigecycline and Other Broad-Spectrum Antimicrobials Tested against Serine Carbapenemase- and Metallo-β-Lactamase-Producing Enterobacteriaceae: Report from the SENTRY Antimicrobial Surveillance Program

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01114-07 ◽

2007 ◽

Vol 52 (2) ◽

pp. 570-573 ◽

Cited By ~ 108

Author(s):

Mariana Castanheira ◽

Hélio S. Sader ◽

Lalitagauri M. Deshpande ◽

Thomas R. Fritsche ◽

Ronald N. Jones

Keyword(s):

Antimicrobial Agents ◽

Rank Order ◽

Polymyxin B ◽

The United States ◽

Multidrug Resistant ◽

Antimicrobial Activities ◽

Surveillance Program ◽

Medical Centers ◽

Antimicrobial Surveillance

ABSTRACT A total of 104 carbapenemase (serine- and metallo-β-lactamase [MβL])-producing strains of the Enterobacteriaceae family collected from 2000 to 2005 in medical centers distributed worldwide were tested against tigecycline and 25 comparators by reference broth microdilution methods. The most frequent carbapenemase was KPC-2 or -3 (73 strains), followed by VIM-1 (14), IMP-1 (11), SME-2 (5), and NMC-A (1). All serine carbapenemases were detected in the United States, while MβL-producing strains were isolated in Europe. Carbapenemase-producing Enterobacteriaceae showed high rates of resistance to most antimicrobial agents tested. The rank order of in vitro activity against these strains was as follows: tigecycline (100.0% susceptible) > polymyxin B (88.1%) > amikacin (73.0%) > imipenem (37.5%). Tigecycline was very active (MIC90, 1 μg/ml) against this significant, contemporary collection of well-characterized strains and appears to be an excellent option compared to the polymyxins for treatment of infections caused by these multidrug-resistant Enterobacteriaceae.

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1369. Oritavancin Activity Against Methicillin-Resistant S. aureus (MRSA) Isolates Causing Skin and Skin Structure Infections in US Hospitals (2017-2019)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1561 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S770-S771

Author(s):

Cecilia G Carvalhaes ◽

Helio S Sader ◽

Dee Shortridge ◽

Jennifer M Streit ◽

Rodrigo E Mendes

Keyword(s):

Multidrug Resistant ◽

Vitro Activity ◽

In Vitro Activity ◽

Services Research ◽

Department Of Health ◽

Medical Centers ◽

The Us ◽

Us Fda ◽

Research Grant

Abstract Background MRSA remains an important cause of community-onset (CA) and nosocomial (NA)- SSSI. Oritavancin (ORI) is a lipoglycopeptide antibiotic with activity against S. aureus, including MRSA and multidrug-resistant (MDR) strains. ORI was approved for clinical use by the US FDA to treat ABSSSI with a single 1,200 mg infusion over 1 (Kimyrsa) or 3 (Orbactiv) hours. This study evaluated the activity of ORI against MRSA isolates causing SSSI from US medical centers. Methods A total of 3,792 S. aureus isolates were consecutively collected (1 per patient) from 31 medical centers in 2017-2019 and tested for susceptibility (S) to ORI and comparators using CLSI broth microdilution methods. Among 1,582 (41.7%) MRSA isolates, 1,379 (87.2%) were reported as CA-MRSA and 203 (12.8%) as NA-MRSA. CA-MRSA isolates were evaluated by resistance (R) subgroups, including clindamycin (CLI-R; n=283; 20.5%), levofloxacin (LEV-R; n=831; 60.3%), MDR (non-susceptible to ≥3 classes of agents; n=816; 59.2%), and extensively drug resistant (XDR; non-susceptible to ≥5 classes; n=47; 3.4%). Results Overall, ORI inhibited 99.9% of all S. aureus isolates at the susceptible breakpoint (≤0.12 mg/L; 99.9% of MSSA and 100% of MRSA; Table). S rates were generally comparable between NA-MRSA and CA-MRSA isolates for ORI (100%S) and linezolid (LZD, 100%S) but lower susceptibility was observed for NA-MRSA compared to CA-MRSA for CLI (71.9%S vs. 79.1%S), LEV (31.0%S vs. 39.4%S), and trimethoprim-sulfamethoxazole (TMP-SMX; 91.1%S vs. 96.9%S). ORI was active against MRSA (MIC50/90, 0.03/0.03 mg/L), regardless of infection status (NA, MIC50/90, 0.03/0.06 mg/L; CA, MIC50/90, 0.03/0.03 mg/L). ORI and LZD remained active (100%S) against all CA-MRSA subsets: CLI-R, LEV-R, MDR, and XDR. Limited activity of CLI (69.9%S) and LEV (13.1%S) was observed against MRSA and each R subset, whereas TMP-SMX had >90%S for all MSSA, MRSA, and R subsets, except XDR. Conclusion ORI exhibited potent in vitro activity against MRSA, regardless of the infection onset or R subset, in contrast to many comparators that lack activity against both, CA-MRSA and NA-MRSA. This in vitro activity, combined with the infusion time options provided to clinicians, suggests ORI is a favorable agent for treating SSSI in the US caused by MRSA, including MDR and XDR strains. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support, Contract no. HHSO100201600002C)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Dee Shortridge, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support) Jennifer M. Streit, BS, GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)

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1262. Antimicrobial Activity of Gepotidacin against Clinical Isolates of Escherichia coli and Staphylococcus saprophyticus Collected Worldwide in 2019

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1446 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S647-S648

Author(s):

S J Ryan Arends ◽

Deborah Butler ◽

Nicole Scangarella-Oman ◽

Mariana Castanheira ◽

Rodrigo E Mendes

Keyword(s):

Escherichia Coli ◽

Chemical Diversity ◽

Clinical Isolates ◽

Asia Pacific ◽

Surveillance Program ◽

Services Research ◽

Staphylococcus Saprophyticus ◽

Tract Infections ◽

Research Grant

Abstract Background Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in Phase 3 clinical development for the treatment of gonorrhea and uncomplicated urinary tract infections (UTI). This study reports on interim results from a global surveillance program to monitor the in vitro activity of gepotidacin and comparator agents when tested against contemporary Escherichia coli (EC) and Staphylococcus saprophyticus (SSAP) clinical isolates collected from patients with UTIs worldwide as part of the SENTRY Antimicrobial Surveillance Program. Methods A total of 1,467 EC and 92 SSAP isolates were collected from 73 medical centers located in US (38), Europe (27), Asia-Pacific region (4), and Latin America (4). These isolates were tested for susceptibility by reference methods in a central laboratory (JMI Laboratories). MIC results for gepotidacin and comparators were interpreted as per US FDA and EUCAST criteria. Isolates were from UTIs, 70% of which were from ambulatory, outpatient, emergency, and family practice medical services. Results Gepotidacin (MIC50/90, 2/4 mg/L) displayed activity against 1,467 EC isolates with 98.2% of all observed MICs ≤ 4 mg/L. Susceptibility rates of trimethoprim-sulfamethoxazole (TMP-SMX; MIC50/90, ≤ .12/ > 16 mg/L), ciprofloxacin (MIC50/90, 0.015/ > 4 mg/L), and amoxicillin-clavulanate (MIC50/90, 8/16 mg/L) were 67.1%, 72.9%, and 78.7% (CLSI), respectively. Greater susceptibility against EC isolates was seen for fosfomycin (MIC50/90, 0.5/1 mg/L; 99.0%S), nitrofurantoin (MIC50/90, 16/32 mg/L; 97.4%S), and meropenem (≤ 0.015/0.03 mg/L; 100%S). An ESBL phenotype was observed in 15.3% of EC isolates; gepotidacin (MIC50/90, 2/4 mg/L) remained active against these isolates. Gepotidacin (MIC50/90, 0.06/0.12 mg/L) also was active against 92 SSAP isolates, with 100% of MICs ≤ 0.25 mg/L. Susceptibility of SSAP isolates to TMP-SMX, ciprofloxacin, or nitrofurantoin was greater than 98.8% (CLSI), while fosfomycin showed little activity (MIC50/90, 64/ > 256 mg/L; 98.9% R [EUCAST]). Conclusion Gepotidacin demonstrated potent activity against contemporary Escherichia coli, including ESBL-producing isolates and S. saprophyticus isolates collected worldwide. Table 1 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) Deborah Butler, n/a, GlaxoSmithKline (Employee) Nicole Scangarella-Oman, MS, GlaxoSmithKline plc. (Employee, Shareholder) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

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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)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1770 ◽

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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