scholarly journals 710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S319-S320
Author(s):  
Chelsea E Jones ◽  
Ellen G Kline ◽  
Minh-Hong Nguyen ◽  
Cornelius J Clancy ◽  
Ryan K Shields
Keyword(s):  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Disk Diffusion ◽  
In Vitro Activity ◽  
Testing Methods ◽  
And Performance ◽  
Susceptibility Breakpoint

Abstract Background Eravacycline (ERV) is a recently-approved, fully synthetic fluorocycline agent that demonstrates broad in vitro activity against multidrug-resistant pathogens. We sought to compare the activity of ERV with minocycline (MIN) and tigecycline (TGC) against diverse CRE clinical isolates, and to evaluate the performance of commercially-available susceptibility testing methods. Methods ERV, MIN, and TGC minimum inhibitory concentrations (MICs) were determined in triplicate by broth microdilution against previously characterized CRE isolates. ERV susceptibility was also measured by disk diffusion (20 µg disk; Mast Group) and MIC test strips (MTS; Liofilchem) according to manufacturer instructions. Results 148 CRE were tested, including 92 K. pneumoniae, 32 Enterobacter spp, 11 E. coli, 5 C. freundii, 4 K. oxytoca, and 4 S. marcescens. 72% of isolates harbored blaKPC, which encoded KPC-2 (n = 33), KPC-3 (n = 48), and other KPC variants (n = 22). 77% and 19% of isolates were resistant to meropenem and ceftazidime–avibactam, respectively. By BMD, the ERV, MIN, and TGC MIC range, MIC50 and MIC90 for shown in the Table. ERV MICs were ≥2-fold lower than MIN and TGC against 99% and 43% of isolates, respectively. ERV MICs did not vary by species or KPC-subtype. ERV MICs determined by BMD and MTS were well-correlated showing 89% essential agreement (MIC within one 2-fold dilution; Figure). The rate of categorical agreement (CA) was 73%. By comparison, the CA rate between BMD and disk diffusion was 78%. By both MTS and disk diffusion methods, susceptibility results clustered on either side of the susceptibility breakpoint. 50% of disk diffusion zones clustered between 14 and 16 millimeters (mm), which is 1 mm on either side of the susceptibility breakpoint (≥15 mm). Conclusion This study confirms the in vitro activity of ERV against CRE clinical isolates, which is comparable to TGC. ERV MTS demonstrated high rates of EA, but lower rates of CA. Clinicians should be aware of the nuances of ERV susceptibility testing and recognize that the modal distribution of ERV MICs against CRE lies on either side of the susceptibility breakpoint. Disclosures All authors: No reported disclosures.

scholarly journals 1280. In-Vitro Activity of Cefiderocol, Imipenem/Relebactam, & Ceftazidime/Avibactam in Ceftolozane/Tazobactam Resistant Strains of Multidrug Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S655-S655
Author(s):  
Daniel Navas ◽  
Angela Charles ◽  
Amy Carr ◽  
Jose Alexander
Keyword(s):  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Resistance Testing ◽  
Clinical Samples ◽  
In Vitro Activity ◽  
Carbapenemase Gene ◽  
Resistant Strains

Abstract Background The activity of imipenem/relebactam (I/R), ceftazidime/avibactam (CZA) and cefiderocol (FDC) were evaluated against clinical isolates of multidrug resistant (MDR) strains of P. aeruginosa which was resistant to ceftolozane/tazobactam (C/T). The recent increase of MDR P. aeruginosa strains isolated from clinical samples has prompted research and development of new antimicrobials that can withstand its multiple resistance mechanisms. C/T is an effective option for treatment of MDR P. aeruginosa in our facility with only 10% of resistance in MDR strains, but the emergence of resistance may occur due to the presence of a carbapenemase gene or an ampC mutation. Methods Antimicrobial susceptibility testing for C/T Etest® (bioMérieux, Inc.) were performed on all MDR strains initially screened by the VITEK2® (bioMérieux, Inc.). 10% (n=20) of all MDR isolates were resistant to C/T by the CLSI 2019 breakpoints. These resistant isolates were tested for presence of a carbapenemase gene using the GeneXpert CARBA-R (Cepheid®) PCR and against CZA Etest® (bioMérieux, Inc.) I/R gradient strips (Liofilchem®) and FDC broth microdilution (Thermo Scientific™ Sensititre™). Results A total of 20 clinical isolates of MDR P. aeruginosa resistant to C/T were tested following standardized CLSI protocols and techniques. All 20 isolates were screened for the presence of a carbapenemase gene (blaVIM, blaNDM, blaKPC, blaOXA-48, blaIMP). A blaVIM gene was detected in 6 (30%) out of 20 isolates. FDC demonstrated the greatest activity with 85% (n=17) of susceptible isolates (CLSI MIC <4µg/dL). CZA (CLSI MIC <8µg/dL) and I/R (FDA MIC <2µg/dL) showed 15% (n=3) and 10% (n=2) of susceptible isolates respectively. FDC was active against all 6 blaVIM isolates, where all 6 strains were resistant to CZA and I/R as expected. 3 isolates tested non-susceptible against FDC; additional characterization was not performed at this time. Conclusion Based on these results, FDC demonstrated the greatest in-vitro activity against C/T resistant strains of MDR P. aeruginosa. FDC also demonstrated activity against all 6 MDR P. aeruginosa carrying blaVIM gene. FDC is a strong option to consider on MDR P. aeruginosa strains based on a resistance testing algorithm and a cost/effective protocol. Disclosures All Authors: No reported disclosures

scholarly journals In Vitro Activity of Cefepime against Multidrug-Resistant Gram-Negative Bacilli, Viridans Group Streptococci andStreptococcus pneumoniaefrom a Cross-Canada Surveillance Study

1999 ◽  
Vol 10 (2) ◽  
pp. 122-127 ◽  
Author(s):  
Donald E Low ◽  
Joyce de Azavedo ◽  
Canadian Bacterial Surveillance Network ◽  
Ross Davidson
Keyword(s):  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Study ◽  
National Committee ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Resistance Rates ◽  
Viridans Group Streptococci

OBJECTIVE: To determine the in vitro activity of cefepime against multidrug-resistant Gram-negative bacilli and Gram-positive cocci obtained from an ongoing cross-Canada surveillance study.DESIGN: Clinical isolates of aerobic Gram-negative bacilli with inducible and constitutive chromosomally mediated cephalosporinases, viridans group streptococci andStreptococcus pneumoniaewere collected from laboratories serving hospitals, nursing homes and physician offices in the community from across Canada during 1996 and 1997. Laboratories were asked to submit only clinically relevant nonduplicate isolates for susceptibility testing. In vitro antimicrobial susceptibility testing was carried out on all isolates of Gram-negative and viridans group streptococci.S pneumoniaewere characterized as penicillin susceptible, intermediately resistant or highly resistant. Nonsusceptible isolates were defined as being intermediately or highly resistant (minimal inhibitory concentrations [MIC] greater than 0.06 mg/L). Only isolates ofS pneumoniaethat were nonsusceptible to penicillin were selected for further study. MICs were determined using a microbroth dilution technique according to the National Committee of Clinical Laboratory Standards.RESULTS: A total of 727 Gram-negative bacilli samples were collected. No resistance to cefepime was detected withCitrobacter freundii,Serratia marcescens,Morganella morganiiandEnterobacterspecies. Of these strains,Enterobacterspecies andC freundiiwere the most resistant to ceftazidime, cefotaxime and ceftriaxone with MIC90Sof 32 mg/L or greater and resistance rates of 6% or greater. Resistance rates ofPseudomonas aeruginosaandAcinetobacterspecies to cefepime were 4.8% and 3%, respectively. The two organisms had similar rates of resistance to ceftazidime. Less than 3% of the Gram-negative bacilli were resistant to imipenem and meropenem. There were 153 viridans group streptococci, of which 22 (14.4%) were resistant to penicillin. Of 1287S pneumoniaesamples, 193 (15%) were nonsusceptible to penicillin. Cefepime, ceftriaxone and cefotaxime had comparable activity against all isolates of viridans group streptococci andS pneumoniae.CONCLUSIONS: Cefepime demonstrated excellent in vitro activity against Gram-negative bacilli with inducible and constitutive chromosomally mediated cephalosporinases, and had equal or superior activity versus comparator beta-lactams against all isolates of viridans group streptococci andS pneumoniae.

In vitro activity of olorofim against clinical isolates of Scedosporium species and Lomentospora prolificans using EUCAST and CLSI methodologies

2020 ◽  
Vol 75 (12) ◽  
pp. 3582-3585
Author(s):  
Olga Rivero-Menendez ◽  
Manuel Cuenca-Estrella ◽  
Ana Alastruey-Izquierdo
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Scedosporium Apiospermum ◽  
In Vitro Activity ◽  
Scedosporium Dehoogii ◽  
Scedosporium Species

Abstract Objectives To evaluate the in vitro activity of olorofim, a new broad-spectrum antifungal with a novel mechanism of action, against a collection of 123 Spanish clinical isolates belonging to five Scedosporium species and Lomentospora prolificans. Methods The activity of olorofim against Scedosporium apiospermum (n = 30), Scedosporium boydii (n = 30), Scedosporium ellipsoideum (n = 10), Scedosporium aurantiacum (n = 20), Scedosporium dehoogii (n = 3) and Lomentospora prolificans (n = 30) was compared with that of amphotericin B, voriconazole, isavuconazole and micafungin by performing EUCAST and CLSI reference methods for antifungal susceptibility testing. Results Amphotericin B and isavuconazole showed MICs ≥2 mg/L for all the species evaluated and voriconazole was moderately active (GM, MIC50 and MIC90 values ≤2 mg/L) against all of them except L. prolificans. Micafungin was effective against S. apiospermum complex strains, but exhibited elevated MECs for S. dehoogii and S. aurantiacum. Olorofim showed low MICs for all the Scedosporium strains tested (GM values were lower than 0.130 and 0.339 by the EUCAST method and the CLSI method, respectively, for all of the species), including those belonging to the MDR species L. prolificans, for which GM values were 0.115 and 0.225 mg/L by the EUCAST method and the CLSI method, respectively, while the GMs for the rest of the antifungals evaluated were higher than 3.732 mg/L using both methodologies. Conclusions Olorofim displayed promising in vitro activity against the Scedosporium and L. prolificans strains tested, some of which have reduced susceptibility to the antifungals that are currently in use.

scholarly journals 598. In Vitro Activity of Aztreonam in Combination with Ceftazidime–Avibactam, Amoxicillin–Clavulanate, and Piperacillin–Tazobactam vs. NDM-Producing Escherichia coli and Klebsiella pneumoniae Clinical Isolates

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S281-S281
Author(s):  
Andrew Walkty ◽  
James Karlowsky
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Disk Diffusion ◽  
In Vitro Activity ◽  
Zone Diameter ◽  
Amoxicillin Clavulanate ◽  
Lactamase Inhibitor

Abstract Background There are limited options available for the treatment of infections caused by Enterobacteriaceae that produce an NDM metallo-β-lactamase. The purpose of this study was to compare the in vitro activity of aztreonam in combination with three different β-lactam/β-lactamase inhibitors (ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin–tazobactam) vs. NDM-positive Enterobacteriaceae clinical isolates. Methods Seven Escherichia coli and three Klebsiella pneumoniae clinical isolates (all NDM-positive by PCR) were included in this study. The in vitro activities of ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin–tazobactam, and aztreonam were determined by disk diffusion as described by CLSI. For synergy testing, disks containing a β-lactamase inhibitor (ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin tazobactam) were applied to Mueller–Hinton agar plates inoculated with the test organisms, and the plates were incubated for 1 hour. The disks were then removed and aztreonam disks were dropped on the previous disk sites. The plates were then incubated as per standard CLSI recommendations for disk diffusion testing. Results All ten isolates demonstrated phenotypic resistance to aztreonam, amoxicillin-clavulanate, and piperacillin–tazobactam, and eight were resistant to ceftazidime–avibactam (CLSI breakpoints). The zone diameter observed for aztreonam in combination with ceftazidime–avibactam was greater than for either antimicrobial on its own for nine isolates. Seven isolates (70%) had susceptibility to aztreonam restored (zone diameter ≥21 mm) in the presence of avibactam. Aztreonam in combination with amoxicillin-clavulanate demonstrated in increase in zone diameter for all isolates relative to the zone for each antimicrobial alone, but only two (20%) had aztreonam susceptibility restored. Aztreonam susceptibility was not restored for any of the isolates in combination with piperacillin–tazobactam. Conclusion Of the three β-lactam/β-lactamase inhibitor-aztreonam combinations evaluated, ceftazidime–avibactam plus aztreonam demonstrated the greatest in vitro activity vs. NDM-producing Enterobacteriaceae. Disclosures All authors: No reported disclosures.

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

scholarly journals In vitro activity of the new β-lactamase inhibitors relebactam and vaborbactam in combination with β-lactams against Mycobacterium abscessus complex clinical isolates

2018 ◽  
Author(s):  
Amit Kaushik ◽  
Nicole C. Ammerman ◽  
Jin Lee ◽  
Olumide Martins ◽  
Barry N Kreiswirth ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Phase Iii ◽  
In Vitro Activity ◽  
Intrinsic Resistance ◽  
Phase Iii Trials ◽  
Lactamase Inhibitor

Pulmonary disease due to infection with Mycobacterium abscessus complex (MABC) is notoriously difficult to treat, in large part due to MABC’s intrinsic resistance to most antibiotics, including β-lactams. MABC organisms express a broad-spectrum β-lactamase that is resistant to traditional β-lactam-based β-lactamase inhibitors but inhibited by a newer non-β-lactam-based β-lactamase inhibitor, avibactam. Consequently, the susceptibility of MABC to some β-lactams is increased in the presence of avibactam. Therefore, we hypothesized that two new non-β-lactam-based β-lactamase inhibitors, relebactam and vaborbactam, would also increase susceptibility of MABC to β-lactams. The objective of the present study was to evaluate the in vitro activity of various marketed β-lactams alone and in combination with either relebactam or vaborbactam against multidrug-resistant MABC clinical isolates. Our data demonstrate that both β-lactamase inhibitors significantly improved the anti-MABC activity of many carbapenems (including imipenem and meropenem) and cephalosporins (including cefepime, ceftaroline, and cefuroxime). As a meropenem/vaborbactam combination is now marketed and an imipenem/relebactam combination is currently in phase III trials, these fixed combinations may become the β-lactams of choice for the treatment of MABC infections. Furthermore, given the evolving interest in dual β-lactam regimens, our results identify select cephalosporins, such as cefuroxime, with superior activity in the presence of a β-lactamase inhibitor, deserving of further evaluation in combination with these carbapenem/β-lactamase inhibitor products.

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 In vitro activity of Ro 19-5247 (T-2525) and interpretive criteria for disk diffusion susceptibility testing.

1987 ◽  
Vol 25 (7) ◽  
pp. 1186-1190 ◽  
Author(s):  
G Beskid ◽  
V Fallat ◽  
J Siebelist ◽  
J W Durkin ◽  
E R Lipschitz ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Vitro Activity ◽  
Disk Diffusion ◽  
In Vitro Activity
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