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

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

Abstract Background Meropenem-vaborbactam (MVB) was recently approved in Europe for the treatment of complicated UTIs, including acute pyelonephritis, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP), and bacteremia. KPC-producing Enterobacterales (ENT) isolates have disseminated worldwide. We analysed the activity of MVB and single-agent comparators against 6,846 ENT isolates from patients hospitalised with pneumonia (PHP) including VAP in European hospitals (2014–2019). Methods Among 6,846 ENT clinical isolates from PHP collected in 40 European hospitals located in 20 countries that were susceptibility (S) tested using reference broth microdilution methods. Of the carbapenem-resistant isolates submitted to whole genome sequencing, 75 carried blaKPC. ENT isolates were also characterized for an extended spectrum beta-lactamase (ESBL) phenotype as described (CLSI, 2020). EUCAST (2020) interpretive criteria were used. %S from patients in the intensive care unit (ICU), ICU patients with VAP, and non-ICU isolates were also analysed. Results The most common ENT pathogens isolated from PHP were Klebsiella pneumoniae (KPN; n=1,877) and Escherichia coli (EC; n=1,646). The %S of MVB and comparators to ENT, ICU, ICU/VAP, and non-ICU are shown in the table. Overall, 98.2% of ENT were S to MVB. For 3,218 ENT isolates from ICU patients, MVB %S was 96.6% and for 2,627 non-ICU isolates MVB %S was 98.5%. The %S of comparators for ICU vs non-ICU isolates were similar, except for levofloxacin. 29 KPC-producing isolates were from ICU (11 from VAP), 46 were from non-ICU. Most KPC-producing isolates were KPN (n=71; 54 blaKPC-3, 16 blaKPC-2 and 1 blaKPC-12). 4 EC contained blaKPC-3. KPC were from 7 countries, Italy had the highest number of KPC-producing isolates at 42 (56%). MVB inhibited 100% of KPC-producing isolates. Amikacin was the most active comparator against all ENT (94.2%S); colistin was the most active comparator against KPC-producing isolates (79.7%S). Conclusion These results demonstrate MVB has potent activity against ENT isolates from PHP including those producing KPC enzymes and suggest MVB is a useful treatment option for ICU and non-ICU PHP including VAP. Table 1 Disclosures Leonard R. Duncan, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Dept of Health and Human Services (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

scholarly journals Antimicrobial Activity of Ceftolozane–Tazobactam Tested against Contemporary (2012–2016) Enterobacteriaceae and Pseudomonas aeruginosa from ICU vs. non-ICU Isolates Collected in US Medical Centers

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S366-S366
Author(s):  
Dee Shortridge ◽  
Leonard R Duncan ◽  
Michael A Pfaller ◽  
Robert K Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
The United States ◽  
Icu Patients ◽  
Medical Centers ◽  
Hospital Acquired Pneumonia ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Hospital Acquired ◽  
Lactamase Inhibitor ◽  
Research Grant

Abstract Background Ceftolozane-tazobactam (C-T) is a combination of a novel antipseudomonal cephalosporin and a well-described β-lactamase inhibitor. C-T was approved by the United States (US) Food and Drug Administration in 2014 for complicated urinary tract infections, including acute pyelonephritis and complicated intra-abdominal infections. C-T is currently in clinical trials for the treatment of hospital-acquired pneumonia. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. This study compares the activities of C-T and comparators against GN isolates from ICU patients and non-ICU patients. Methods A total of 3,100 GN ICU isolates and 3,271 isolates from non-ICU patients were collected from 30 US hospitals in 2012–2016. Isolates were tested for susceptibility (S) to C-T and comparators by CLSI broth microdilution methodology in a central monitoring laboratory. Other antibiotics tested included amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), meropenem (MER), and piperacillin-tazobactam (TZP). CLSI (2017) interpretive criteria were used for all except COL with Enterobacteriaceae (ENT), for which EUCAST (2017) criteria were used. Results The most common ENT species from ICU and non-ICU patients were similar. The 3 most common ENT for ICU and non-ICU isolates were Klebsiella pneumoniae, 24.1% and 25.8%; Escherichia coli, 19.4% and 18.2%; and Serratia marcescens, 14.7% and 14.3%, respectively. The most common non-enteric species was Pseudomonas aeruginosa (PSA) for ICU and non-ICU (72.7% and 78.2%). ICU ENT isolates generally had a lower %S than non-ICU (Table). ENT showed more variability than PSA for %S between ICU and non-ICU. Conclusion For ENT overall, MER and AMK were the most active, followed by C-T. Comparing ICU and non-ICU, MER and C-T were slightly more active vs. non-ICU ENT, while AMK %S was similar for both. For PSA, COL was the most active; C-T and AMK were similar. Activities between ICU and non-ICU isolates were similar for C-T and COL while AMK was more active vs. ICU isolates, and MER was more active vs. non-ICU. C-T showed potent activity against ICU and non-ICU isolates for ENT and PSA. Disclosures D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant

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

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

Abstract Background Meropenem-vaborbactam (MVB) is a combination of a carbapenem and a b-lactamase inhibitor active against β-lactamases including serine carbapenemases. MVB recently was approved in the US and Europe for the treatment of complicated UTIs, including acute pyelonephritis, and is approved in Europe for treatment of complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, ventilator-associated pneumonia, and bacteremia. Carbapenemase-producing Enterobacterales (ENT) isolates, particularly Klebsiella pneumoniae (KPN), have disseminated worldwide and are considered endemic in various countries. Carbapenem-resistant (CR) KPN outbreaks have been associated with KPN sequence-type 258 (ST258). Globally, 60-70% of KPC-producing KPN belong to ST258. In this study, we examined the susceptibilities of ST258 isolates collected as a part of the SENTRY global surveillance program. Methods KPN isolates from 2016-2019 were susceptibility tested by reference broth microdilution methods. The results were interpreted using CLSI 2020 breakpoints. The sequence type and presence of carbapenemases were determined by whole genome sequencing and analysis. Results 130 KPN ST258 isolates were identified in 6 countries. All isolates were extremely drug resistant (XDR, susceptible to < = 1 agent in 2 or fewer drug classes). 76.2% were CR, and 71 isolates contained blaKPC-2, 25 blaKPC-3 and 1 blaKPC-12. One isolate contained blaNDM-1. The US had the most ST258 isolates (n=56), of which 22 produced KPC-2 and 19 produced KPC-3. Greece had 32 isolates, with 17 KPC-2 and 5 KPC-3. Brazil had 22 isolates, 17 with KPC-2. The single NDM-1 producing isolate was from Argentina. Susceptibilities to MVB and comparators by country are shown in the table. MVB inhibited 99.2% of the isolates and was the most active agent overall, only 23.1% were meropenem susceptible. Tigecycline was the most active comparator with 98.5% susceptible. Conclusion These results demonstrate MVB has potent activity against the internationally disseminated KPN clone ST258 including those producing KPC. MVB may be useful for the treatment of infections caused by XDR K. pneumoniae. Table 1 Disclosures Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

scholarly journals 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 In Vitro Activity of Doripenem, a Carbapenem for the Treatment of Challenging Infections Caused by Gram-Negative Bacteria, against Recent Clinical Isolates from the United States

2008 ◽  
Vol 52 (12) ◽  
pp. 4388-4399 ◽  
Author(s):  
Chris M. Pillar ◽  
Mohana K. Torres ◽  
Nina P. Brown ◽  
Dineshchandra Shah ◽  
Daniel F. Sahm
Keyword(s):  
The United States ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
Ventilator Associated Pneumonia ◽  
Coagulase Negative Staphylococci ◽  
Hospital Acquired Pneumonia ◽  
Abdominal Infections ◽  
Hospital Acquired ◽  
Gram Positive Cocci

ABSTRACT Doripenem, a 1β-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (μg/ml) were established by broth microdilution. By MIC90, doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, ≤0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC90 of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum β-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC90/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC90 = 2, 89.1%S) was twice as active by MIC90 as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including β-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of β-lactam resistance.

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

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

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

scholarly journals Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Nathan Peiffer-Smadja ◽  
Lila Bouadma ◽  
Vincent Mathy ◽  
Kahina Allouche ◽  
Juliette Patrier ◽  
...  
Keyword(s):  
Multiplex Pcr ◽  
Ventilator Associated Pneumonia ◽  
Icu Patients ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired

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

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

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

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

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

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

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