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 681. In vitro Activity of the β-Lactamase Inhibitor QPX7728 in Combination with Several β-Lactams Against Acinetobacter baumannii (AB) and Pseudomonas aeruginosa (PSA)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S310-S311 ◽  
Author(s):  
Olga Lomovskaya ◽  
Jill Lindley ◽  
Debora Rubio-Aparicio ◽  
Kirk J Nelson ◽  
Mariana Castanheira
Keyword(s):  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method ◽  
Data Representative ◽  
Lactamase Inhibitor

Abstract Background QPX7728 (QPX) is a novel broad-spectrum boron-containing inhibitor of serine- and metallo-β-lactamases (MBLs). We evaluated the in vitro activity of QPX combined with several β-lactams against carbapenem-resistant AB (CRAB) and PSA clinical isolates with varying β-lactam resistance mechanisms. Methods A total of 503 CRAB (meropenem [MEM] MIC ≥8 µg/mL) and 762 PSA clinical isolates were tested by the reference broth microdilution method against β-lactams alone and combined with QPX (4 µg/mL and 8 µg/mL). PSA isolates were selected to represent the normal distribution of MEM, ceftazidime–avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance according to 2017 surveillance data (representative panel). Additionally, 262 PSA isolates that were either nonsusceptible (NS) to MEM (MIC, ≥4 µg/mL) or to TOL-TAZ (MIC, ≥8 µg/mL), or resistant (R) to CAZ-AVI (MIC, ≥16 µg/mL) (challenge panel) were also tested. Within this 262 strain challenge set, 56 strains carried MBLs and the majority also had nonfunctional OprD. Results Against CRAB, QPX at 4 and 8 µg/mL increased the potency of all β-lactams tested. MEM-QPX was the most potent combination (table) displaying MIC50/MIC90 at 1/8 and 0.5/4 µg/mL with QPX at fixed 4 and 8 µg/mL, respectively. Susceptibility (S) to MEM was restored in >95% of strains. Against the 500 PSA from the representative panel, S for all QPX combinations was >90%. For the challenge panel, TOL-QPX and piperacillin (PIP)-QPX were the most potent combinations, restoring S in 76–77% of strains. TOL-QPX and MEM-QPX or cefepime (FEP)-QPX restored the MIC values to S rates when applying the CLSI breakpoint for the compound alone (comparison purposes only) in ~90% and ~75% of non-MBL-producing strains, respectively, vs. 60–70% for TOL-TAZ and CAZ-AVI. PIP-QPX reduce the MIC values to S values for PIP-TAZ in ~60% of MBL-producing strains vs. 20–30% and 3–7% for other QPX combinations and non-QPX tested combinations, respectively. Conclusion Combinations of QPX with various β-lactam antibiotics displayed potent activity against CRAB and resistant PSA isolates and warrant further investigation. 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 In Vitro Activity of the New Glycopeptide LY333328 against Multiply Resistant Gram-Positive Clinical Isolates

1998 ◽  
Vol 42 (9) ◽  
pp. 2452-2455 ◽  
Author(s):  
Fernando García-Garrote ◽  
Emilia Cercenado ◽  
Luis Alcalá ◽  
Emilio Bouza
Keyword(s):  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Resistant Strains

ABSTRACT The in vitro activity of LY333328 was compared with those of vancomycin and teicoplanin against 425 gram-positive clinical isolates, including a variety of multiply resistant strains. LY333328 at ≤4 μg/ml inhibited all microorganisms tested, including methicillin- and teicoplanin-resistant staphylococci, glycopeptide-resistant enterococci, penicillin- and multiply resistant pneumococci, and viridans and beta-hemolytic streptococci.

scholarly journals In Vitro Activity of the Histatin Derivative P-113 against Multidrug-Resistant Pathogens Responsible for Pneumonia in Immunocompromised Patients

2005 ◽  
Vol 49 (3) ◽  
pp. 1249-1252 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Wojciech Kamysz ◽  
Giuseppina D'Amato ◽  
Carmela Silvestri ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Vitro Activity ◽  
Immunocompromised Patients ◽  
In Vitro Activity ◽  
Beta Lactams ◽  
Gram Negative ◽  
Resistant Strains ◽  
Multidrug Resistant Pathogens ◽  
Gram Negative Organisms

ABSTRACT The in vitro activity of the histatin derivative P-113, alone or combined with eight antibiotics, was investigated against multidrug-resistant strains isolated from clinical specimens of immunocompromised patients with pneumonia. The gram-negative isolates were susceptible to P-113. S. aureus showed less susceptibility. Synergy was demonstrated when P-113 was combined with beta-lactams against gram-negative organisms.

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 Omadacycline and Comparator Compounds Against Gram-positive Isolates Collected in the USA During 2016 as Part of a Global Surveillance Program

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S374-S374
Author(s):  
Michael D Huband ◽  
Michael a Pfaller ◽  
Helio S Sader ◽  
Robert K Flamm
Keyword(s):  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Ionization Mass ◽  
In Vitro Activity ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Resistant Strains ◽  
Research Grant

Abstract Background Omadacycline (OMC) is a broad spectrum aminomethylcycline antibacterial in late stage clinical development (PO and IV formulations) for treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). OMC has potent in vitro activity against gram-positive (GP) pathogens expressing common resistance mechanisms to penicillins, tetracyclines, fluoroquinolones and macrolides. Methods A total of 4,122 GP isolates were collected in 2016 from 30 USA medical centers and included 2,366 staphylococci, 1,252 streptococci and 504 enterococci. A single isolate/patient/infection episode was included. Identifications were confirmed by matrix-assisted laser desorption/ionization mass spectrometry and susceptibility (S) testing was performed using reference broth microdilution methods. Results OMC was equally active against methicillin-susceptible (55.1% MSSA) and -resistant (44.9% MRSA) Staphylococcus aureus (SA; MIC50/90, 0.12/0.25 µg/mL). All SA were S to daptomycin (DAP), linezolid (LZD) and vancomycin (VAN). In MRSA, S was lower for levofloxacin (LEV; 28.2%), clindamycin (CLI; 69.9%), and erythromycin (ERY; 10.9%). OMC (MIC50/90, 0.12/0.5 µg/mL) and tigecycline (TGC; MIC50/90, 0.06/12 µg/mL) were the most active agents against coagulase-negative staphylococci (CoNS) and methicillin-R CoNS. S. pneumoniae (including penicillin- [12.8% resistant], ceftriaxone- and ERY-resistant strains), viridans group streptococci (VGS) and β-hemolytic streptococci (including ERY and tetracycline resistant strains) were inhibited by low levels of OMC (MIC50/90 0.06/0.06–0.12 µg/mL) and TGC (MIC50/90 0.03–0.06/0.06–0.12 µg/mL). OMC was highly potent against enterococci (MIC50/90 0.12/0.25 µg/mL) including vancomycin-R isolates. Vancomycin resistance rates were 4.3% and 66.5% in E. faecalis and E. faecium, respectively. Conclusion OMC demonstrated potent activity against susceptible and resistant GP pathogens often associated with ABSSSI and CABP including staphylococci, S. pneumoniae, β-hemolytic streptococci, VGS and enterococci. These data support further omadacycline clinical studies, especially in infections where resistant GP isolates occur. Disclosures M. D. Huband, Paratek Pharma, LLC: Research Contractor, Research grant; M. A. Pfaller, Paratek Pharma, LLC: Research Contractor, Research grant; H. S. Sader, Paratek Pharma, LLC: Research Contractor, Research grant R. K. Flamm, Paratek Pharma, LLC: Research Contractor, Research grant

Evaluation of the in vitro activity of new polymyxin B analogue SPR206 against clinical MDR, colistin-resistant and tigecycline-resistant Gram-negative bacilli

2020 ◽  
Vol 75 (9) ◽  
pp. 2609-2615 ◽  
Author(s):  
Yawei Zhang ◽  
Chunjiang Zhao ◽  
Qi Wang ◽  
Xiaojuan Wang ◽  
Hongbin Chen ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Enterobacter Cloacae ◽  
Polymyxin B ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Resistant Strains

Abstract Background SPR206 is a novel polymyxin analogue. Activity against clinical isolates is little documented. Methods A collection of 200 MDR, carbapenem-resistant, tigecycline-resistant, colistin-resistant and non-MDR clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Stenotrophomonas maltophilia was obtained from 50 centres across China (2016–17). All isolates were derived from respiratory tract, urine and blood samples. Strains were purposely selected on the basis of phenotypes, genotypes and specimen origins. MICs of SPR206 and other antimicrobials were determined. Results SPR206 was active against all bacteria tested except colistin-resistant isolates. The MIC50/90 values of SPR206 for colistin-resistant strains were comparable to known polymyxins (16/128 versus 8/128 mg/L). SPR206 exhibited potent activity against colistin-susceptible OXA-producing A. baumannii (MIC50/90 = 0.064/0.125 mg/L), NDM-producing Enterobacteriaceae (MIC50/90 = 0.125/0.25 mg/L) and KPC-2-producing Enterobacteriaceae (MIC50/90 = 0.125/0.5 mg/L). In fact, SPR206 was the most potent agent tested, with 2- to 4-fold lower MICs than colistin and polymyxin B for A. baumannii, P. aeruginosa and Enterobacteriaceae. Additionally, MIC values of SPR206 (MIC50/90 = 0.064/0.125 mg/L) were 16- to 32-fold lower than those of tigecycline (MIC50/90 = 2/2 mg/L) for tigecycline-susceptible carbapenem-resistant A. baumannii. Conclusions SPR206 showed good in vitro activity against MDR, tigecycline-resistant and non-MDR clinical isolates of Gram-negative pathogens. SPR206 also exhibited superior potency to colistin and polymyxin B, with 2- to 4-fold lower MIC50/90 values.

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