scholarly journals 1268. In Vitro Activity of Ceftazidime-Avibactam and Comparators against KPC-Producing Enterobacterales and Pseudomonas aeruginosa Collected in China as Part of the ATLAS Global Surveillance Program in 2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S722-S723
Author(s):  
Mark G G Wise ◽  
Krystyna Kazmierczak ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
The United States ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Independent Contractor ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Class A ◽  
Rapid Spread

Abstract Background Among Gram-negative bacteria, the rapid spread of carbapenemases has limited therapeutic options. Klebsiella pneumoniae carbapenemase (KPC), an Ambler class A serine β-lactamase, presents a particular challenge as it has become widespread, first identified in an isolate collected in the United States and thereafter moving throughout the world, including China. Fortunately, the β-lactamase inhibitor avibactam is a potent inhibitor of KPC, rendering many Enterobacterales and some P. aeruginosa isolates that carry KPC susceptible to ceftazidime-avibactam (CAZ-AVI) in vitro. This study reports on the in vitro activity of CAZ-AVI and comparators against Enterobacterales and P. aeruginosa isolates collected in China as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program in 2019. Methods 1,443 non-duplicate Enterobacterales and 522 P. aeruginosa isolates were collected from 17 clinical sites in China in 2019. Susceptibility testing was done using broth microdilution according to CLSI guidelines and interpreted using CLSI 2021 breakpoints. 143/177 meropenem non-susceptible Enterobacterales isolates and 150/187 meropenem non-susceptible P. aeruginosa isolates were interrogated by whole genome sequencing (WGS; Illumina 2x150 bp reads). Results Enterobacterales isolates exhibited higher % susceptibility (% S) to CAZ-AVI than all comparators tested (96.0% S; Table). The addition of AVI to CAZ resulted in an increase in susceptibility from 61.3% to 96.0% in the overall collection of Enterobacterales isolates. 96.0% of KPC-positive Enterobacterales, and 67.8% of the meropenem non-susceptible sub-population were susceptible to CAZ-AVI, against which comparators were less active (≤42.9 % S). Among P. aeruginosa isolates, 89.8% were susceptible to CAZ-AVI, more than for any comparator except amikacin (AMK; 94.4% S). Against meropenem non-susceptible and KPC-carrying P. aeruginosa sub-populations more were susceptible to CAZ-AVI (75.9% and 83.3% S, respectively) and AMK (87.2% and 100% S, respectively) than to other comparators (≤40.6% and ≤8.3% S, respectively). Results Table Conclusion CAZ-AVI demonstrated very good in vitro activity against Enterobacterales and P. aeruginosa isolates from China, including those that harbor KPC. Disclosures Mark G G. Wise, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

scholarly journals 1569. In Vitro Activity of Ceftazidime-avibactam and Comparator Agents against Enterobacterales and Pseudomonas aeruginosa Collected from Patients with Bloodstream Infections as Part of the ATLAS Global Surveillance Program, 2015-2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S783-S784
Author(s):  
Krystyna Kazmierczak ◽  
Sibylle Lob ◽  
Greg Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Therapeutic Option ◽  
Bloodstream Infections ◽  
The United States ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Independent Contractor

Abstract Background Avibactam (AVI) is a β-lactamase inhibitor with potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. The combination of ceftazidime (CAZ) with AVI has been approved in Europe and in the United States for several indications. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales (Eba) and Pseudomonas aeruginosa (Pae) isolates collected from patients with bloodstream infections as part of the ATLAS surveillance program in 2015-2018. Methods A total of 57048 Eba and 15813 Pae non-duplicate clinically significant isolates, including 7720 Eba and 1286 Pae isolated from bloodstream infections, were collected in 52 countries in Europe, Latin America, Asia/Pacific (excluding mainland China), and the Middle East/Africa region. Susceptibility testing was performed by CLSI broth microdilution. CAZ-AVI was tested at a fixed concentration of 4 µg/ml AVI. Meropenem-nonsusceptible (MEM-NS) Eba and Pae isolates were screened for the presence of β-lactamase genes. Results Susceptibility data are shown in the Table. Percentages of susceptibility (% S) to the tested agents were 0.3-2.9% lower among Eba and Pae from bloodstream infections compared to isolates from combined sources in most cases. CAZ-AVI showed potent in vitro activity against all Eba bloodstream isolates and the CAZ-NS subset (MIC90, 0.5-2 µg/ml, 93.4-98.1% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) because 99% of MEM-NS MBL-negative isolates were susceptible to CAZ-AVI. None of the tested comparators exceeded the activity of CAZ-AVI. CAZ-AVI also showed good in vitro activity against the majority of Pae bloodstream isolates (MIC90, 16 µg/ml, 89.4% S). Activity was reduced against CAZ-NS and MEM-NS subsets (54.2-63.8% S), which included isolates carrying MBLs, but exceeded the activity of CAZ and MEM against these subsets by 26-31 percentage points. Amikacin was the only tested comparator that demonstrated comparable activity against Pae bloodstream isolates. Table Conclusion CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

scholarly journals 1263. In Vitro Activity of Ceftazidime-avibactam and Comparator Agents against Enterobacterales and Pseudomonas aeruginosa Collected from Patients with Bloodstream Infections as Part of the ATLAS Global Surveillance Program, 2017-2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S720-S720
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Therapeutic Option ◽  
Bloodstream Infections ◽  
The United States ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Independent Contractor

Abstract Background Avibactam (AVI) is a β-lactamase inhibitor with potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. The combination of ceftazidime (CAZ) with AVI has been approved in Europe and in the United States for several indications. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales (Eba) and Pseudomonas aeruginosa (Pae) isolates collected from patients with bloodstream infections as part of the ATLAS surveillance program in 2017-2019. Methods A total of 48193 Eba and 15376 Pae non-duplicate clinically significant isolates, including 9224 Eba and 1808 Pae isolated from bloodstream infections, were collected in 53 countries in Europe, Latin America, Asia/Pacific (excluding mainland China), and the Middle East/Africa region. Susceptibility testing was performed by CLSI broth microdilution. CAZ-AVI was tested at a fixed concentration of 4 µg/ml AVI. Meropenem-nonsusceptible (MEM-NS) Eba and Pae isolates were screened for the presence of β-lactamase genes. Results Susceptibility data are shown in the Table. Percentages of susceptibility (% S) to the tested agents were 0.4-3.4% lower among Eba and Pae from bloodstream infections compared to isolates from combined sources in most cases. CAZ-AVI showed potent in vitro activity against all Eba bloodstream isolates and the CAZ-NS subset (MIC90, 0.5-4 µg/ml, 91.7-97.4% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) as 98.1% of MEM-NS MBL-negative isolates were susceptible to CAZ-AVI. None of the tested comparators exceeded the activity of CAZ-AVI. CAZ-AVI also showed good in vitro activity against the majority of Pae bloodstream isolates (MIC90, 16 µg/ml, 89.7% S). Activity was reduced against CAZ-NS and MEM-NS subsets (55.9-63.0% S), which included isolates carrying MBLs, but exceeded the activity of CAZ against MEM-NS and MEM against CAZ-NS by 26-28 percentage points. Amikacin was the only tested comparator that demonstrated comparable activity against Pae bloodstream isolates. Results Table Conclusion CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

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 693. In Vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Enterobacteriaceae and Pseudomonas aeruginosa Collected From Patients with Bloodstream Infections as Part of the ATLAS Global Surveillance Program, 2014–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S314-S314
Author(s):  
Krystyna Kazmierczak ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Therapeutic Option ◽  
Bloodstream Infections ◽  
The United States ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Susceptibility Data

Abstract Background Avibactam (AVI) is a β-lactamase inhibitor with potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. The combination of ceftazidime (CAZ) with AVI has been approved in Europe and in the United States for several indications. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacteriaceae (Eba) and Pseudomonas aeruginosa (Pae) isolates collected from patients with bloodstream infections as part of the ATLAS surveillance program in 2014–2017. Methods A total of 53416 Eba and 15050 Pae nonduplicate clinically significant isolates, including 5155 Eba and 845 Pae isolated from bloodstream infections, were collected by 167 hospital laboratories in 36 countries in Europe, Latin America, Asia/Pacific (excluding China), and the Middle East/Africa region. Susceptibility testing was performed by CLSI broth microdilution. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Meropenem-nonsusceptible (MEM-NS) Eba and Pae isolates were screened for the presence of β-lactamase genes. Results Susceptibility data are shown in the Table. Percentages of susceptibility (% S) to the tested agents were 0.2–2.8% lower among Eba and Pae from bloodstream infections compared with isolates from combined sources in most cases. CAZ-AVI showed potent in vitro activity against all Eba bloodstream isolates and subsets of CAZ-NS and colistin-resistant (CST-R) isolates (MIC90, 0.5–2 µg/mL, 96.0–100% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) because all MEM-NS MBL-negative isolates were susceptible to CAZ-AVI. CAZ-AVI also showed good in vitro activity against the majority of Pae bloodstream isolates (MIC90, 16 µg/mL, 89.5% S). Activity was reduced against CAZ-NS, MEM-NS and CST-R subsets (53.7–85.0% S), which included isolates carrying MBLs, but exceeded the activity of CAZ and MEM against these subsets by 15–65%. CST and amikacin were the only tested comparators that demonstrated comparable or greater activity against Pae bloodstream isolates. Conclusion CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates. Disclosures All authors: No reported disclosures.

scholarly journals 1353. In Vitro Activity of Lefamulin (LEF) Against Bacterial Pathogens Commonly Causing Community-Acquired Bacterial Pneumonia (CABP): 2016 SENTRY Data From the United States

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S414-S414 ◽  
Author(s):  
Susanne Paukner ◽  
Robert K Flamm ◽  
Steven P Gelone ◽  
Helio S Sader
Keyword(s):  
United States ◽  
Ribosomal Subunit ◽  
The United States ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
Medical Centers ◽  
Tract Infections

Abstract Background LEF, the first pleuromutilin antibiotic for IV and oral use in humans, is in Phase 3 clinical trials for the treatment of CABP in adults. In the first of these to be completed, LEF demonstrated noninferiority to moxifloxacin ± linezolid. LEF inhibits bacterial translation by binding the 50S ribosomal subunit at the A- and P-sites in the peptidyl transferase center. CABP is a leading cause of infectious diseases in the United States and increasing antibacterial resistance complicates its treatment. This study investigated the in vitro activity of LEF and comparators against a contemporary set of bacterial respiratory pathogens collected in the United States. Methods Isolates (n = 1674, 1/patient) were collected from 32 medical centers in the United States as part of the SENTRY Surveillance Program. LEF and comparators were tested by CLSI broth microdilution methods, and susceptibility was determined using the CLSI (2018) breakpoints. Results LEF was the most active compound against Streptococcus pneumoniae (MIC50/90 of 0.12/0.12 µg/mL), and its activity was not affected by resistance to other antibiotic classes. S. pneumoniae isolates were susceptible to levofloxacin (99.1%) and ceftriaxone (97.7%), whereas only 53.9%, 63.9%, and 80.4% of isolates were susceptible to macrolides, penicillin (oral), and tetracycline, respectively. LEF also showed potent activity against Staphylococcus aureus (MIC50/90 of 0.06/0.12 µg/mL), including methicillin-resistant (MRSA) isolates (MIC50/90 of 0.06/0.12 µg/mL, 87.1% resistant to erythromycin), Haemophilus influenzae, (MIC50/90 of 0.5/1 µg/mL, 26.9% β-lactamase producing), and Moraxella catarrhalis (MIC50/90 0.06/0.06 µg/mL, 96.5% β-lactamase positive) (figure). Conclusion LEF displayed potent in vitro activity against a contemporary collection of respiratory pathogens from the United States. LEF was active regardless of resistance phenotype to other antibiotic classes including β-lactams, tetracyclines, or macrolides. These results further support the clinical development of lefamulin for the treatment of CABP or other respiratory tract infections. Disclosures S. Paukner, Nabriva: Employee and Shareholder, Salary. R. K. Flamm, Nabriva: Research Contractor, Research grant. S. P. Gelone, Nabriva Therapeutics: Employee, Equity, Shareholder and Salary. Achaogen: Shareholder, Equity, Shareholder. H. S. Sader, Nabriva Therapeutics: Research Contractor, Research support.

scholarly journals 1570. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales from ICU and Non-ICU Wards Collected in Latin America and Globally as part of the ATLAS Surveillance Program 2017-2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S784-S784
Author(s):  
Sibylle Lob ◽  
Krystyna Kazmierczak ◽  
Greg Stone ◽  
Daniel F Sahm
Keyword(s):  
Antimicrobial Activity ◽  
Latin America ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Independent Contractor ◽  
Global Average ◽  
Valuable Treatment

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with activity against Enterobacterales producing class A, C and some class D β-lactamases. Resistance caused by these β-lactamases is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales isolates from patients in ICU and non-ICU wards. Methods Non-duplicate clinical isolates were collected in 2017-2018 from patients in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC >1 µg/ml. Results The activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global Enterobacterales were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI, which inhibited ≥97% of isolates from both ward types. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 66.5% and 68.1% of ICU and non-ICU isolates, respectively (of which 31.8% and 30.8%, respectively, carried metallo-β-lactamases [MBLs]). CAZ-AVI inhibited >97% of MEM-NS MBL-negative isolates collected globally. Antimicrobial activity against all Enterobacterales from both ICU and non-ICU wards in Latin America (LA) was generally similar to the global average. Among MEM-NS isolates, antimicrobial activity of CAZ-AVI and TGC was higher in LA than the global average among isolates from both ward types, at least partly because of a lower proportion of MBL-positive isolates in this subset (15.8% and 17.9% in ICU and non-ICUs, respectively). CAZ-AVI inhibited 100% of MEM-NS MBL-negative isolates from LA. Table Conclusion CAZ-AVI provides a valuable treatment option for infections caused by Enterobacterales that do not carry MBLs, including those among patients in ICU wards, where antimicrobial resistance is typically higher. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

scholarly journals 1245. In Vitro Activities of Ceftaroline and Comparator Agents Against Bacterial Pathogens Collected from Patients with Skin and Skin Structure Infections: ATLAS Global Surveillance Program 2012-2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S711-S711
Author(s):  
Meredith Hackel ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
Klebsiella Oxytoca ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Bacterial Isolates ◽  
Independent Contractor ◽  
Ceftaroline Fosamil ◽  
Skin Structure ◽  
Dose Dependent

Abstract Background Ceftaroline fosamil, the prodrug of ceftaroline, is a parenteral cephem approved for the treatment of patients with skin and skin structure infections (SSSIs) caused by Staphylococcus aureus (both methicillin-susceptible [MSSA] and methicillin-resistant [MRSA] isolates), β-hemolytic streptococci (Streptococcus pyogenes, S. agalactiae, S. dysgalactiae), and select species of Enterobacterales (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca). The current study is part of the ATLAS (Antimicrobial Testing Leadership and Surveillance) program and evaluated the current activities of ceftaroline and comparator agents against commonly encountered bacterial isolates associated with SSSIs. Methods From 2012 to 2019 the ATLAS program received 124,694 bacterial isolates that had been cultured by 493 clinical laboratories in 71 countries from samples of patients diagnosed with SSSIs. All isolates were transported to IHMA, (Schaumburg, IL, USA) where their identities were confirmed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing performed following standardized CLSI broth microdilution methodology (M07). Percent susceptibilities were determined using 2021 CLSI MIC breakpoints. Phenotypic extended-spectrum β-lactamase (ESBL) screening and confirmatory testing were performed using the CLSI M100 method. Results The in vitro activity of ceftaroline is summarized in the following table. Overall, >99.9% of MSSA and 92.8% of MRSA from SSSI were susceptible to ceftaroline (MIC ≤1 µg/ml); 7.1% of MRSA isolates were ceftaroline-susceptible dose-dependent (MIC 2-4 µg/ml) with greatest proportion being from Chile (53.3% of 392 isolates), S. Korea (29.3% of 321 isolates), and China (24.7% of 652 isolates). Twelve ceftaroline-resistant MRSA were observed, consisting of 11 of 109 isolates from Thailand (10.1%) and 1 of 161 from China (0.6%). All S. pyogenes and 88.0% of ESBL-negative Enterobacterales were susceptible to ceftaroline. Results Table Conclusion Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with SSSIs. Disclosures Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

scholarly journals 1081. Antimicrobial Activity of Dalbavancin Tested Against Gram-Positive Organisms Isolated From Patients With Infective Endocarditis in United States and European Medical Centers

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S323-S323
Author(s):  
Helio S Sader ◽  
Rodrigo E Mendes ◽  
Michael A Pfaller ◽  
Robert K Flamm
Keyword(s):  
United States ◽  
Infective Endocarditis ◽  
The United States ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Research Support ◽  
Gram Positive ◽  
Medical Centers

Abstract Background The management of endocarditis requires aggressive and prolonged antimicrobial treatment. Dalbavancin (DALBA) has demonstrated potent in vitro activity against Gram-positive (GP) organisms commonly responsible for endocarditis and is being evaluated for treatment of complicated bacteremia and infective endocarditis. Methods A total of 626 GP organisms were collected from patients with a diagnosis of bacterial endocarditis in the United States (n = 222) and Europe (n = 404) from 2007 to 2017 via the SENTRY Antimicrobial Surveillance Program and were tested for susceptibility (S) against DALBA and comparators by CLSI broth microdilution. Results The most common organisms were S. aureus (48.4%), E. faecalis (EF; 19.6%), and viridans group streptococci (VGS; 12.5%). DALBA and daptomycin (DAPTO) showed complete activity (100.0%S) against S. aureus, but DALBA MICs were 4- to 8-fold lower (table). Linezolid (LZD) and teicoplanin were also active against all SA; whereas vancomycin (VAN) and trimethoprim–sulfamethoxazole were active against 99.7% of isolates. Ceftaroline (CPT) exhibited potent activity against methicillin-susceptible S. aureus (MSSA; MIC90, 0.25 mg/L; 100.0%S) and inhibited 78.4% of methicillin-resistant S. aureus (MRSA) isolates at ≤1 mg/L. All EF isolates were S to ampicillin, DAPTO, and LZD, whereas 97.6% (120/123) of isolates were S to DALBA (MIC90, 0.06 mg/L) and 96.7%S to VAN (MIC90, 2 mg/L). Against EF, DALBA MIC values were 16- to 32-fold lower than DAPTO and VAN. All VGS and coagulase-negative staphylococcal (CoNS) isolates were S to DALBA, DAPTO, VAN, and LZD, and the highest CPT MICs were 0.5 mg/L for VGS and 4 mg/L for CoNS (93.5% inhibited at ≤1 mg/L). Against E. faecium (EFM), 65.7% of isolates were inhibited at ≤0.25 mg/L of DALBA and 62.9% were VAN-S. All EFM were S to DAPTO and LNZ. β-Hemolytic streptococci (BHS) was S to most antimicrobial agents, and only 66.7% of S. pneumoniae (SPN) isolates were PEN-S at ≤0.06 mg/L. Conclusion DALBA exhibited potent in vitro activity against a large collection of GP isolates recovered from patients with endocarditis in the United States and Europe medical centers. These results support further investigations to determine the role of DALBA in the treatment of infective endocarditis. Disclosures H. S. Sader, Allergan: Research Contractor, Research support. R. E. Mendes, Allergan: Research Contractor, Research support. M. A. Pfaller, Allergan: Research Contractor, Research support. R. K. Flamm, Allergan: Research Contractor, Research support.

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