scholarly journals In vitro activity of ceftolozane/tazobactam versus antimicrobial non-susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from across Canada as part of the CANWARD study, 2008–16

2017 ◽  
Vol 73 (3) ◽  
pp. 703-708 ◽  
Author(s):  
Andrew Walkty ◽  
Heather Adam ◽  
Melanie Baxter ◽  
Philippe Lagacé-Wiens ◽  
James A Karlowsky ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity

scholarly journals In Vitro Activity of Ceftolozane-Tazobactam vs. Antimicrobial Non-Susceptible Pseudomonas aeruginosa Clinical Isolates Obtained from Across Canada as Part of the CANWARD Study, 2008–2016

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S372-S372
Author(s):  
Andrew Walkty ◽  
Heather J Adam ◽  
Melanie Baxter ◽  
Philippe Lagace-Wiens ◽  
James Karlowsky ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Research Support ◽  
Research Relationship ◽  
Inhibitor Combination ◽  
Patient Infection

Abstract Background Ceftolozane-tazobactam (C/T) is a novel β-lactam β-lactamase inhibitor combination with a broad spectrum of activity that includes Pseudomonas aeruginosa. The purpose of this study was to evaluate the in vitro activity of C/T and relevant comparators vs. a large collection of antimicrobial non-susceptible (NS) P. aeruginosa clinical isolates obtained from patients across Canada (CANWARD, 2008–2016). Methods From January 2008 to December 2016, inclusive, 12 to 15 sentinel hospitals across Canada submitted clinical isolates from patients attending ERs, medical and surgical wards, hospital clinics, and ICUs (CANWARD). Each center was asked to annually submit clinical isolates (consecutive, one per patient/infection site) from blood, respiratory, urine, and wound infections. Susceptibility testing was performed using broth microdilution as described by CLSI. Multidrug-resistant (MDR) P. aeruginosa were defined as isolates that tested NS to at least one antimicrobial from ≥3 classes. Extensively drug-resistant (XDR) P. aeruginosa were defined as isolates that tested NS to at least one antimicrobial from ≥5 classes. Results 3229 P. aeruginosa isolates were obtained as a part of CANWARD. The in vitro activity of C/T and relevant comparators is presented below. Conclusion C/T demonstrated excellent in vitro activity vs. antimicrobial NS P. aeruginosa clinical isolates, including MDR, XDR, and meropenem NS subsets. It may prove useful in the treatment of infections caused by these organisms. Disclosures D. Hoban, Abbott: Research relationship, Research support Achaogen: Research relationship, Research support Astellas: Research relationship, Research support Merck Canada: Research relationship, Research support Merck USA: Research relationship, Research support Paratek Pharma: Research relationship, Research support Pharmascience: Research relationship, Research support Sunovion: Research relationship, Research support Tetraphase: Research relationship, Research support The Medicines Co.: Research relationship, Research support Zoetis: Research relationship, Research support; G. Zhanel, Achaogen: Research relationship, Research support Astellas: Research relationship, Research support Merck Canada: Research relationship, Research support Merck USA: Research relationship, Research support Paratek Pharma: Research relationship, Research support Pharmascience: Research relationship, Research support Sunovion: Research relationship, Research support Tetraphase: Research relationship, Research support The Medicines Co.: Research relationship, Research support Zoetis: Research relationship, Research support

In vitro activity of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa in the planktonic and biofilm states

2016 ◽  
Vol 85 (3) ◽  
pp. 356-359 ◽  
Author(s):  
Antonio L. Velez Perez ◽  
Suzannah M. Schmidt-Malan ◽  
Peggy C. Kohner ◽  
Melissa J. Karau ◽  
Kerryl E. Greenwood-Quaintance ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity

scholarly journals In vitro activity of biapenem and other carbapenems against Russian clinical isolates of Pseudomonas aeruginosa, Acinetobacter spp., and Enterobacterales

2021 ◽  
Vol 23 (3) ◽  
pp. 280-291
Author(s):  
Roman S. Kozlov ◽  
Ilya S. Azyzov ◽  
Andrey V. Dekhnich ◽  
Nataly V. Ivanchik ◽  
Alexey Yu. Kuzmenkov ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Central Research Institute ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Central Research ◽  
In Vitro Activity ◽  
Mechanisms Of Resistance ◽  
Minimal Inhibitory Concentrations ◽  
Acinetobacter Spp

Objective. To evaluate in vitro activity of biapenem and other clinically available carbapenems against Russian clinical isolates of Enterobacterales, Pseudomonas aeruginosa и Acinetobacter spp., including isolates with acquired fermentative mechanisms of resistance to β-lactams. Materials and Methods. A total of 3139 Enterobacterales isolates, 793 P. aeruginosa isolates and 634 Acinetobacter spp. isolates from hospitalized patients in 63 hospitals from 35 Russian cities were included in the study during 2018-2019. Minimal inhibitory concentrations (MIC) for biapenem and other antimicrobials were determined in accordance with ISO 20776-1:2006. Carbapenemases genes were detected by commercially available real-time PCR kits AmpliSens® MDR KPC/OXA-48-FL and AmpliSens® MDR MBL-FL (Central Research Institute of Epidemiology, Russia). Data analysis and reporting was performed using AMRcloud online platform (www.amrcloud.net). Results. For all tested Escherichia coli isolates MIC50/90 were 0.06/0.125 mg/l for biapenem, 0.125⁄0.25 mg/l for imipenem, and 0.06/0.06 mg/l for meropenem. When MIC50/90 for ertapenem (0.015/0.125 mg/l for all isolates tested) were comparable to those of biapenem, a greater number of nosocomial E. coli isolates had MIC >4 mg/l for ertapenem (3.6%) than for biapenem (2.6%). MIC50/90 of Klebsiella pneumoniae for biapenem were 0.5⁄16 mg/l, for both imipenem and meropenem – 0.5⁄32 mg/l, for ertapenem – 2⁄32 mg/l. Resistance to oxyimino-β-lactams had no significant influence on activity of biapenem against Enterobacterales isolates. For 321 carbapenemase-producing K. pneumoniae isolates (ОХА-48 – 63.9%, NDM – 27.7%) biapenem has shown no advantages over imipenem and meropenem. МПК50/90 for nosocomial and community-acquired P. aeruginosa isolates were 8⁄64 mg/l and 0,5⁄16 mg/l for biapenem, 8⁄128 mg/l and 1⁄16 mg/l – for imipenem, 16⁄64 mg/l and 0,5⁄32 mg/l – for meropenem. All carbapenems, including biapenem, had very low in vitro activity against carbapenemaseproducing P. aeruginosa isolates. МПК50/90 of Acinetobacter spp. were 64⁄128 mg/l for biapenem, 64⁄128 mg/l – for imipenem, and 128⁄128 mg/l – for meropenem. Conclusions. According to the MIC distributions and MICs50/90 values independently of the presence of fermentative mechanisms of resistance to β-lactams, in vitro activity of biapenem against Russian clinical isolates of Enterobacterales, P. aeruginosa and Acinetobacter spp. was comparable to those of imipenem and meropenem.

scholarly journals 521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S251-S251 ◽  
Author(s):  
Twisha S Patel ◽  
Keith S Kaye ◽  
Jay Krishnan ◽  
Vince Marshall ◽  
John Mills ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Real World ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Limited Data ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Inhibitor Combination

Abstract Background Meropenem/vaborbactam (MV) is a carbapenem and boronic acid–based β-lactamase inhibitor combination product with potent in vitro activity against Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. As carbapenem resistance in Pseudomonas aeruginosa (PSA) is primarily driven by porin mutations, efflux pumps, or infrequently by metallo-β-lactamases, vaborbactam is not expected to improve the in vitro activity of meropenem (MEM) against this pathogen. However, limited data currently exists assessing the comparative in vitro activity of MEM and MV. The purpose of this study was to compare the in vitro activity of MV and MEM against a large real-world sample of clinical isolates of PSA where both MV and MEM are routinely tested on all isolates. Methods All cultures from patient infections with PSA from May 2018 to February 2019 at Michigan Medicine were included. Minimum inhibitory concentrations (MICs) were determined using TREK broth microdilution panels and isolates were considered susceptible to MV if the MIC was ≤4 mg/L and MEM if the MIC was ≤2 mg/L. Results A total of 2,967 isolates of PSA from clinical specimens were included. 80.5% of isolates were susceptible to MEM (MIC50 ≤1 mg/L and MIC90 8 mg/L, range ≤1 to >32 mg/L) at a breakpoint of ≤2 mg/L and 86.3% at a breakpoint of ≤4 mg/L; whereas 90.8% of isolates were susceptible to MV (MIC50 ≤1 mg/L and MIC90 4 mg/L, range ≤1 to >8 mg/L). Of those displaying MEM MIC >2 mg/L, 53% (n = 308) were susceptible to MV. Of those displaying MEM MIC >4 mg/L, 33.7% (n = 137) were susceptible to MV. Although the majority of MIC discordances in MEM-R/MV-S isolates were 1–2 doubling dilutions, 52 (38%) isolates had their meropenem MIC decreased ≥3 doubling dilutions by the addition of vaborbactam suggesting significant inhibitory activity (Table 1). Conclusion We found a surprising number of PSA isolates with discordant MV and MEM susceptibility at Michigan Medicine. Further exploration of mechanisms of meropenem resistance in these isolates is warranted. Disclosures All authors: No reported disclosures.

scholarly journals 1581. Comparative In Vitro Activity of Ceftolozane/tazobactam and Comparator Agents Against Enterobacteriaceae and Pseudomonas Aeruginosa Clinical Isolates in Colombia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S577-S577
Author(s):  
Cristhian Hernández-Gómez ◽  
Elsa De La Cadena ◽  
Maria F Mojica ◽  
Adriana Correa ◽  
Marcela Perengüez ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Healthcare Associated ◽  
Resistance Rates ◽  
Outer Membrane Permeability

Abstract Background Multidrug-resistant Enterobacteriaceae (Ent) and Pseudomonas aeruginosa (Pae) are involved in a considerable number of healthcare-associated infections, thus representing a therapeutic challenge. Ceftolozane–tazobactam (C/T) is a combination of a novel cephalosporin with a known β-lactamase inhibitor. Ceftolozane has high affinity for penicillin-binding proteins, improved outer membrane permeability, increased stability against efflux and enhanced stability against chromosomal AmpC β-lactamases compared with other β-lactam antibiotics. This agent is not active against carbapenemases. We evaluated the in vitro activity of C/T against clinical isolates of Ent and Pae collected from 2016- 2017 and compared it to the activity of broad-spectrum antimicrobial agents. Methods 1.644 Ent and Pae non-duplicate clinical isolates were collected in 13 medical centers located in 12 Colombian cities. Minimum inhibitory concentrations (MIC) were performed by broth microdilution and interpreted according to current CLSI guidelines. Isolates tested included 813 Escherichia coli (Eco), 441 Klebsiella pneumoniae (Kpn), 82 Enterobacter spp., (Enb); 60 Serratia marcescens (Sma) and 248 Pae. Comparator agents were ceftriaxone (CRO), cefotaxime (CTX), ceftazidime (CAZ), cefepime (FEP), piperacillin/tazobactam (TZP), ertapenem (ETP), imipenem (IMI), meropenem (MEM). Results Susceptibilities to C/T and comparators of 4 Ent species and Pae are shown in Table 1. Compared with other β-lactams such as CRO, CAZ, TZP, and FEP, C/T had considerably higher susceptibility rates against ESBL, non-carbapenem-resistant (CR) Eco and Kpn isolates. C/T MIC50/90 were: Eco (≤1/≤1); Kpn (≤1/128); Enb (≤1/64); Sma (≤1/≥256); Pae (≤1/≥256). In the case of P.aeruginosa despite the high resistance rates observed in the study, C/T had the best susceptibility, even higher than the carbapenems. Conclusion Overall, C/T demonstrated higher in vitro activity than currently available cephalosporins and TZP when tested against Ent and Pae. C/T provides an important treatment option against infections caused by non-carbapenemase producing Gram-negative pathogens. Further studies are warranted to identify an emerging mechanism of resistance in Colombia. Disclosures All authors: No reported disclosures.

scholarly journals 522. In Vitro Antimicrobial Activity of Ceftazidime/Avibactam Compared with Ceftolozane/Tazobactam Against Real-world Clinical Isolates of Pseudomonas aeruginosa at a Large Academic Tertiary Care Hospital

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S251-S252
Author(s):  
Twisha S Patel ◽  
Keith S Kaye ◽  
Vince Marshall ◽  
Jay Krishnan ◽  
John Mills ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Real World ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Care Hospital ◽  
In Vitro Activity ◽  
Routine Testing

Abstract Background Ceftazidime/avibactam (CZA) and ceftolozane-tazobactam (CT) are new additions to the antibiotic armamentarium with activity against gram-negative pathogens, most notably drug-resistant Pseudomonas aeruginosa (PSA). The purpose of this study was to compare the in vitro activity of CZA and CT against a large real-world sample of clinical isolates of PSA displaying different phenotypes of resistance to conventional β-lactams at an institution where both CZA and CT are routinely tested on all isolates. Methods All cultures from patient infections with PSA from May 2018 to February 2019 at Michigan Medicine were included. Minimum inhibitory concentrations (MICs) for all β-lactams were determined using TREK broth microdilution panels and isolates were considered susceptible to CZA if the MIC was ≤8 mg/L and CT if the MIC was ≤4 mg/L. Results A total of 2,972 isolates of PSA from clinical specimens were included. Table 1 compares CZA and CT susceptibility, MIC50, MIC90, and MIC range for all isolates including those displaying resistance to various β-lactams. Among all isolates of PSA, CZA (96.2% susceptible) was slightly more active than CT (94.2%) and both agents were ~10% more active than the closest comparator (ceftazidime, 86.6%). In vitro activity of cefepime, piperacillin/tazobactam, and meropenem were 84.8%, 78%, and 80.3%, respectively. The activity of both CZA and CT dropped significantly among isolates with pan-β-lactam resistance (i.e., resistance to all conventional anti-pseudomonal β lactams, PBR) but CZA remained more active than CT (59.4% vs. 41.5%, P < 0.001). Of isolates displaying resistance to CT, 84 (48.6%) were susceptible to CZA. However, of those with resistance to CZA, only 24 (21.2%) were susceptible to CT (Table 2). Conclusion CZA was the most active β-lactam against PSA isolates at Michigan Medicine. Among PSA with PBR, CZA demonstrated superior activity compared with CT. Additionally, a significant number of isolates with resistance to CT were susceptible to CZA. Our findings are unique compared with other published reports where CT has consistently demonstrated greater activity than CZA against resistant P. aeruginosa and suggest routine testing of both CT and CZA should occur. Disclosures All authors: No reported disclosures.

scholarly journals Susceptibility of clinical Enterobacterales and Pseudomonas aeruginosa isolates to ceftazidimeavibactam in Russia: multicenter local laboratory databased surveillance

2021 ◽  
Vol 23 (3) ◽  
pp. 264-278 ◽  
Author(s):  
Mikhail V. Edelstein ◽  
Elena Yu. Skleenova ◽  
Ivan V. Trushin ◽  
Alexey Yu. Kuzmenkov ◽  
Alexey А. Martinovich ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Susceptibility Testing ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Diffusion Method ◽  
Case Report Form ◽  
In Vitro Activity ◽  
Disk Diffusion Method ◽  
Online Platform

Objective. To assess the in vitro activity of ceftazidime-avibactam against clinical Enterobacterales and Pseudomonas aeruginosa isolates in various regions of Russia based on results of local susceptibility testing by disk diffusion method. Materials and Methods. Overall, 160 laboratories located in 61 Russian cities participated in this surveillance during 2018-2020. All consecutive clinical isolates of Enterobacterales and Pseudomonas aeruginosa in each participating laboratory were included in the study. Ceftazidime-avibactam susceptibility testing was done by disc-diffusion method in accordance with current EUCAST recommendations. Susceptibility data for carbapenems and III-IV generation cephalosporins, as well as results of carbapenemases detection, were also reported, if available. All the data were recorded in electronic case report form developed on the OpenClinica online platform (www.openclinica.com). Data analysis and reporting were done using AMRcloud online platform (https://amrcloud.net/). Results. In total, we received information on antimicrobial susceptibility of 22,121 isolates, including 17,456 (78.9%) Enterobacterales and 4,665 (21.1%) P. aeruginosa. Less than 9% of Enterobacterales isolates were resistant to ceftazidime-avibactam. At the same time rates of resistance to ceftazidime, cefotaxime, cefepime, ertapenem, imipenem, and meropenem were 54.1%, 58.9%, 59.4%, 41.4%, 23.9%, and 21.3%. Among Enterobacterales the highest level of resistance to ceftazidime-avibactam was detected in K. pneumoniae (16.5%), lowest – in E. coli (2.1%). Some increase of resistance to ceftazidimeavibactam was noted during the study – from 7.8% in 2018-2019 to 9.6% in 2020 (p = 0.0001). Rate of resistance to ceftazidime-avibactam in P. aeruginosa was 33.1%. At the same time rates of resistance to ceftazidime, cefepime, imipenem, and meropenem were 51.1%, 54.5%, 50%, and 47.3%. During the study there was statistically significant decrease in resistance to ceftazidime-avibactam in P. aeruginosa (p = 0.0001). Resistance rates for all beta-lactams for both Enterobacterales and P. aeruginosa were higher in nosocomial isolates than in community-acquired isolates. Conclusions. Ceftazidime-avibactam demonstrated significantly higher in vitro activity against Enterobacterales and P. aeruginosa Russian clinical isolates comparing with commonly used carbapenems and extended spectrum cephalosporins. Access for all study data available at the AMRcloud online platform (https://amrcloud.net/ru/project/cazavi-1-2/).

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