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

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

Abstract Background CoNS represent an important cause of bloodstream infections, osteoarticular infections, foreign-body-associated infections and endocarditis. We evaluated the frequency of CoNS species and the activity of dalbavancin (DALB) in comparison to vancomycin (VAN), daptomycin (DAP) and other agents against a large collection of CoNS isolates. Methods 5,088 CoNS isolates causing clinically significant infection were consecutively collected from 122 medical centers located in the United States (79 centers) and Europe (43 centers in 21 nations) over 6 years (2014-2019) and susceptibility tested by CLSI broth microdilution methods against DALB and comparators. Species identification was confirmed by MALDI-TOF. Results Most isolates were from bloodstream (BSI; 53.5%) or skin/skin structure infections (28.5%). S. epidermidis was the most common species overall (54.6%; Table) and for BSI (61.3%). The second most common species were S. lugdunensis overall (12.3%) and S. hominis for BSI (14.7%). DALB (MIC50/90, 0.03/0.06 mg/L) inhibited > 99.9% of CoNS isolates at the susceptible (S) breakpoint established by CLSI for S. aureus (≤ 0.25 mg/L) and was 8-fold more active than DAP (MIC50/90, 0.25/0.5 mg/L; 99.9% S) and 32-fold more active than VAN (MIC50/90, 1/2 mg/L; > 99.9% S). Linezolid was active against 98.7% of isolates (MIC50/90, 0.5/1 mg/L). All species were inhibited at ≤0.25 mg/L of DALB, except S. epidermidis (> 99.9%) and S. warneri (98.9%; Table). The most DALB-S species were S. capitis and S. simulans (MIC50/90, 0.015/0.03 mg/L for both species), whereas the highest DALB MIC50/90 values were observed with S. haemolyticus and S. saprophyticus (MIC50/90, 0.06/0.12 mg/L and highest MIC of 0.25 mg/L for both species). In contrast, 47.8% of S. epidermidis and 34.7% S. haemolyticus exhibited decreased susceptibility to VAN (MIC ≥ 2 mg/L), and 23.2% of S. capitis and 28.4% of S. warneri showed decreased susceptibility to DAP (MIC ≥ 1 mg/L). Overall oxacillin-S rate was 39.3%, varying from 3.0% for S. saprophyticus to 95.4% for S. lugdunensis. In general, BSI isolates were slightly less S than non-BSI isolates. Conclusion Antimicrobial susceptibility varied widely among CoNS species. DALB exhibited potent in vitro activity against all CoNS species. Table 1 Disclosures Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) S. J. Ryan Arends, PhD, Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals 1253. In Vitro Activity of Omadacycline against 7000 Bacterial Pathogens from the United States Stratified by Infection Type (2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S644-S644
Author(s):  
Michael D Huband ◽  
Michael A Pfaller ◽  
Jennifer M Streit ◽  
Helio S Sader ◽  
Mariana Castanheira
Keyword(s):  
United States ◽  
The United States ◽  
Chemical Diversity ◽  
Vitro Activity ◽  
Multiple Infection ◽  
In Vitro Activity ◽  
Infection Types ◽  
Center Research ◽  
Research Grant

Abstract Background Omadacycline (OMC) is a new aminomethylcycline antibacterial drug belonging to the tetracycline class, for intravenous or oral administration. It is well tolerated and has proven effective in the treatment of a variety of bacterial infections. OMC is active against bacterial strains expressing the most common clinically relevant tetracycline resistance mechanisms, namely efflux and ribosomal protection. Methods 7,000 clinical isolates were collected during 2019 in the SENTRY Surveillance Program from 31 medical centers in the United States (US). Isolates were obtained from bloodstream infection (23.8%), skin and skin structure infection (21.6%), pneumonia in hospitalized patients (22.7%), urinary tract infection (14.5%), intraabdominal infection (6.2%), community acquired respiratory tract infection (10.3%) and other infection types (0.9%). Identifications were confirmed by MALDI-TOF. One isolate/patient/infection episode was tested. Broth microdilution susceptibility testing was conducted according to CLSI M07 (2018) and M100 (2020) guidelines. Results were interpreted using US FDA and CLSI breakpoint criteria. Results OMC demonstrated potent in vitro activity against Staphylococcus aureus isolates representing multiple infection types (MIC90, 0.12-0.25 mg/L; 94.7%-99.0% susceptible [S]) including MRSA (MIC90, 0.25 mg/L; 96.5% S) (Table). All S. lugdunensis (MIC90, 0.06 mg/L), Enterococcus faecalis (MIC90, 0.12-0.25 mg/L), and Haemophilus influenzae (MIC90, 1 mg/L) isolates were S to OMC. OMC was active against Streptococcus pyogenes isolates from SSSI (MIC90, 0.12 mg/L; 93.3%-98.5%S) including macrolide-resistant (R) strains. Similarly, S. pneumoniae isolates from RTI were S to OMC (MIC90, 0.06-0.12 mg/L; 98.8%-100%S) regardless of resistance to tetracycline or penicillin. Overall, 90.2%-93.6% of Enterobacter cloacae (MIC90, 4 mg/L) and 89.7%-94.7% of Klebsiella pneumoniae (MIC90, 4-8 mg/L) isolates from multiple infection types were S to OMC. Conclusion OMC demonstrated potent in vitro activity against Gram-positive and -negative bacterial pathogens from multiple infection types including SSSI and RTI and isolates displaying resistance to tetracycline, macrolides, and penicillin. Table 1 Disclosures Michael A. Pfaller, MD, Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

scholarly journals 1584. In Vitro Activity of Imipenem/Relebactam against Gram-Negative Pathogens from Patients with Bloodstream Infections in the United States and Canada – SMART 2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S789-S790
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
Katherine Young ◽  
Mary Motyl ◽  
Daniel F Sahm
Keyword(s):  
United States ◽  
Bloodstream Infections ◽  
The United States ◽  
Common Species ◽  
Surveillance Program ◽  
Independent Contractor ◽  
Gram Negative ◽  
The Us ◽  
Gram Negative Organisms

Abstract Background Relebactam (REL) inhibits class A and C β-lactamases, including KPC, and was approved in the United States combined with imipenem (IMI) and cilastatin for complicated urinary tract and intraabdominal infections. We evaluated the activity of IMI/REL against non-Morganellaceae (NME) and P. aeruginosa collected as part of the global SMART surveillance program from patients with bloodstream infections (BSI) in the US and Canada. Methods In 2018, 24 US and 8 Canadian hospitals each collected up to 50 consecutive aerobic or facultative gram-negative pathogens from patients with BSI. MICs were determined using CLSI broth microdilution and interpreted with 2020 CLSI breakpoints. Multidrug-resistance (MDR) was defined as resistance to ≥3 of the following sentinel drugs: amikacin, aztreonam, cefepime, ceftazidime (NME only), ciprofloxacin, colistin, imipenem, and piperacillin/tazobactam. Results The 5 most common species among 1463 collected BSI isolates were E. coli (46.9%), K. pneumoniae (16.0%), P. aeruginosa (8.5%), P. mirabilis (4.8%), and E. cloacae (4.3%). Susceptibility to IMI/REL and comparators of selected species and subsets of resistant phenotypes is shown in the table. IMI/REL was active against 99.8% of NME isolates; only meropenem, ceftazidime/avibactam, and amikacin showed comparable activity. Per 2020 CLSI guidelines, Enterobacterales and P. aeruginosa isolates are no longer considered susceptible to colistin. IMI/REL maintained activity against 89-100% of NME isolates that were nonsusceptible (NS) to β-lactams or MDR. Among P. aeruginosa, IMI/REL was active against 94.4% of isolates; a susceptibility rate only exceeded by amikacin. The addition of relebactam lowered the MIC90 for P. aeruginosa from 16 µg/mL to 1 µg/mL. IMI/REL maintained activity against 40-77% of P. aeruginosa isolates NS to β-lactams or MDR; susceptibility rates only exceeded by amikacin. Susceptibility to IMI/REL was similar in the US (99.8% of NME [n=846]; 93.8% of P. aeruginosa [n=96]) and Canada (99.7% of NME [n=339]; 96.4% of P. aeruginosa [n=28]). Table Conclusion In the US and Canada, IMI/REL could provide an important treatment option for patients with BSI caused by resistant gram-negative organisms. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

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 1463. Activity of Delafloxacin against Multi-Drug-Resistant Fastidious Respiratory Pathogens from European Medical Centers (2014-2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S733-S733
Author(s):  
Dee Shorttidge ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Robert K Flamm
Keyword(s):  
Active Agent ◽  
The United States ◽  
Multidrug Resistant ◽  
Respiratory Pathogens ◽  
Services Research ◽  
In Vitro Susceptibility ◽  
Amoxicillin Clavulanate ◽  
Tract Infections ◽  
Research Grant

Abstract Background Delafloxacin (DLX) is an anionic fluoroquinolone (FQ) that has been approved in the United States and in Europe for the treatment of acute bacterial skin and skin structure infections and was recently approved in the US for treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from European hospitals participating in the SENTRY Program during 2014-2019. Methods A total of 2,835 SPN, 1,484 HI, 959 MC, and 20 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014-2019 from European hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and EUCAST (2020) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin (ERY), and tetracycline; other SPN phenotypes were ERY-NS, or penicillin (PEN)-NS. β-lactamase (BL) presence was determined for HI, HP, and MC. Results The activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were the same when tested against the MDR or PEN-NS for SPN phenotypes. ERY-NS isolates had DLX MIC50/90 results of 0.015/0.03 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 1 HP isolate was BL-positive. Conclusion DLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. These data support the utility of DLX in CABP including when caused by antibiotic resistant strains. Table 1 Disclosures 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) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)

scholarly journals 129. Antimicrobial Activity of Ceftazidime–avibactam and Comparator Agents Tested against Gram-Negative Organisms Isolated from Patients with Bloodstream Infections in United States Medical Centers (2017–2018)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S93-S94
Author(s):  
Cecilia G Carvalhaes ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes ◽  
Helio S Sader
Keyword(s):  
United States ◽  
New York ◽  
Bloodstream Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Medical Centers ◽  
Carbapenem Resistant ◽  
Gram Negative Organisms ◽  
Esbl Producers

Abstract Background We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) and P. aeruginosa (PSA) causing bloodstream infections (BSIs) in the United States (US) hospitals. Methods A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017–2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-Lactamase screening was performed by whole-genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype). Results The most common ENT species isolated from BSI were E. coli (EC; 41.9% of ENT), K. pneumoniae (KPN; 24.4%), and E. cloacae (ECL; 8.7%), and the most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.6%S) and meropenem (MEM; 99.3%S). CAZ-AVI was active against all EC and KPN isolates (100.0%S). Only 2 ENT isolates (0.06%) were CAZ-AVI resistant, 2 NDM-1-producing ECL isolated in the New York City area. Ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) showed good activity against EC and KPN (92.2–98.9%S; Table), with limited activity against ECL (81.9–83.7%S). The most common ESBLs were CTX-M-type, which was observed in 93% of ESBL producers (mainly CTX-M-15 [64% of ESBL producers] and CTX-M-27 [13%]), and OXA-1/OXA-30 (42%); 42% of ESBL producers (n = 333, excluding carbapenemase producers) displayed ≥2 ESBL genes, mainly CTX-M-15 and OXA-1/OXA-30 (40% of ESBL producers). The most active agents against ESBL producers were CAZ-AVI (100.0%S), imipenem (99.4%S), and colistin (COL; 99.1%S). Only CAZ-AVI (99.4%S), AMK (96.2%S) and MEM (92.8%S) were active against >90% of multidrug-resistant (MDR) ENT. Among 19 carbapenem-resistant ENT (CRE; 0.6% of ENT), 9 produced a KPC-like, 2 an NDM-1, and 2 an NMC-A; carbapenemase genes were not found in 6 CRE isolates. COL (100.0%S), CAZ-AVI (98.5%S), AMK (98.5%S), C-T (98.1%S), and tobramycin (97.0%S) were very active against PSA. Conclusion CAZ-AVI exhibited potent in vitro activity and great spectrum against ENT (99.9%S) and PSA (98.5%) isolated from patients with BSI from US hospitals. Disclosures All authors: No reported disclosures.

scholarly journals Evaluation of In Vitro Activity of Ceftaroline Tested against Streptococcus pneumoniae Isolates from United States Hospitals: Results from 7 Years of the AWARE Surveillance Program (2010–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S378-S378
Author(s):  
Michael A Pfaller ◽  
Rodrigo E Mendes ◽  
Leonard R Duncan ◽  
Robert K Flamm ◽  
Helio S Sader
Keyword(s):  
United States ◽  
The United States ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Amoxicillin Clavulanate ◽  
Infection Types ◽  
Research Grant

Abstract Background Ceftaroline (CPT) is a broad-spectrum cephalosporin with activity against S. pneumoniae (SPN), including multidrug-resistant (MDR) strains. CPT fosamil is approved for clinical use in the United States (US) to treat community-acquired bacterial pneumonia (CABP). The AWARE Program monitors the in vitro activity of CPT against clinical bacteria from various infection types. We evaluated the activity of CPT against isolated SPN clinical isolates from US hospitals collected in 2010 through 2016. Methods A total of 8,768 isolates were consecutively collected (1 per patient) from 47 medical centers in 2010–2016 and tested for susceptibility (S) to CPT and comparator agents using CLSI broth microdilution methods. Resistant subgroups included isolates that were nonsusceptible (NS) to penicillin (PCN), ceftriaxone (CRO), amoxicillin-clavulanate (AMC), erythromycin (ERY), clindamycin (CM), and levofloxacin (LEV) as well as MDR (NS to ≥3 classes of agents) and extensively drug resistant (XDR; NS to ≥5 classes). Results CPT inhibited 99.99% of SPN isolates at ≤0.5 mg/L (only 1 isolate had a CPT MIC of 1 mg/L) and remained active against all SPN-resistant (R) subgroups, including PCN-NS (8.7% at ≥4 mg/L), CRO-NS (6.9% at ≥2 mg/L), MDR (21.7%), and XDR (8.4%) strains. CPT activity remained stable against all R subgroups each year. MDR and XDR frequency decreased from 25.0% and 14.1% in 2011 to 17.8% and 3.2% in 2015, respectively; and S to PCN, CRO, AMC, CM, trimethoprim-sulfamethoxazole (TMX), and tetracycline (TET) increased in the same period (Table). The CPT-NS isolate had multiple substitutions in the penicillin binding proteins (PBP), mainly PBP2x, when compared with reference sequences, and showed 31 amino acid alterations in MurM. For MDR isolates, CPT (99.9%S), tigecycline (99.9%S), linezolid (100.0%S), and vancomycin (100.0%S) were the most active agents. Conclusion CPT demonstrated potent and consistent (2010–2016) activity against SPN, including several R phenotypes and the less S serotypes. SPN S to many antibiotics increased from 2011 to 2015, but remained stable in 2015–2016. Increases in S rates could be related to the anti-pneumococcal vaccine PVC-13 introduced in 2010. Disclosures M. A. Pfaller, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; H. S. Sader, Allergan: Research Contractor, Research grant

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

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S20-S20
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Michael D Huband ◽  
Dee Shorttidge ◽  
Cecilia G Carvalhaes ◽  
...  
Keyword(s):  
Bloodstream Infections ◽  
The United States ◽  
Chemical Diversity ◽  
Surveillance Program ◽  
E Coli ◽  
Antimicrobial Surveillance ◽  
The Us ◽  
Resistance Rates ◽  
Center Research ◽  
Research Grant

Abstract Background The SENTRY Antimicrobial Surveillance Program monitored the etiology of bloodstream infections (BSI) and other infections worldwide since 1997. We evaluated the results for BSI in the United States (US) and Europe (EU). Methods Organisms were consecutively collected (1/patient) from 79 medical centers located in the US (n=12,748; 35 centers), western EU (W-EU; n=12,198; 29 centers from 10 nations: Belgium, France, Germany, Ireland, Italy, Portugal, Spain, Sweden, Switzerland, and the United Kingdom), and eastern EU (E-EU; n=3,297; 15 centers from 12 nations: Belarus, Croatia, Czech Republic, Greece, Hungary, Israel, Poland, Romania, Russia, Slovakia, Slovenia, and Turkey). Organisms were susceptibility tested by reference broth microdilution methods in a central laboratory. Results The most common organism found was S. aureus in the US and E. coli in W-EU and E-EU (Table). E. coli, S. aureus, and K. pneumoniae represented the top 3 organisms in all 3 regions and accounted for 53.9–54.8% of the collection. Gram-negative bacilli (GNB) represented 48.8% of organisms in the US, 59.8% in W-EU, and 65.6% in E-EU. MRSA rates were higher in US (41.6%) compared to W-EU (24.4%) and E-EU (24.6%). In contrast, susceptibility to ceftriaxone and levofloxacin among E. coli were lower in E-EU (66.4% and 55.8%, respectively) compared to W-EU (83.3% and 73.5%, respectively) and the US (83.0% and 65.8%, respectively). Among K. pneumoniae, susceptibility to ceftriaxone and meropenem were 86.6% and 98.7% in US, 64.3% and 84.7% in W-EU, and 30.2% and 72.5% in E-EU, respectively. CRE rates were lower in US (0.5%) compared to W-EU (2.8%) and very high in E-EU (10.4%). P. aeruginosa susceptibility to piperacillin-tazobactam and meropenem were 84.8% and 83.7% in US, 81.4% and 82.3% in W-EU, and 64.6% and 57.6% in E-EU, respectively. Vancomycin-nonsusceptibility (VRE) rates in the US, W-EU, E-EU were 3.2%, 0.9%, and 2.7% among E. faecalis, and 64.6%, 18.2%, and 30.6% among E. faecium, respectively. Table 1 Conclusion The frequency of GNB was lower in the US compared to W-EU and E-EU. Antimicrobial resistance rates among Gram-positive cocci were higher in the US compared to W-EU and E-EU; whereas, among GNB, resistance rates generally were higher in E-EU compared to W-EU and the US. Disclosures Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

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