scholarly journals Characterization and in vitro activity of a lytic phage RDN37 isolated from community sewage water active against MDR Uropathogenic E. coli

2021 ◽  
Author(s):  
Naveen Chaudhary ◽  
Chandradeo Narayan ◽  
Balvinder Mohan ◽  
Neelam Taneja
Keyword(s):  
Sewage Water ◽  
Vitro Activity ◽  
Lytic Phage ◽  
In Vitro Activity ◽  
E Coli

scholarly journals 1375. In vitro Activity of Cefiderocol and Comparator Agents against Gram-Negative Isolates from Cancer Patients

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S421-S422 ◽  
Author(s):  
Kenneth V I Rolston ◽  
Bahgat Gerges ◽  
Issam Raad ◽  
Samuel L Aitken ◽  
Ruth Reitzel ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Active Agent ◽  
Vitro Activity ◽  
Significant Activity ◽  
In Vitro Activity ◽  
Research Support ◽  
Gram Negative ◽  
E Coli ◽  
Research Grant

Abstract Background Gram-negative bacilli (GNB) are now the predominant cause of bacterial infection in cancer patients (CP). Many GNB are problematic because they have become resistant to commonly used antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin, is active against a wide spectrum of GNB. We evaluated its in vitro activity and that of eleven comparator agents against GNB isolated from CP. Methods A total of 341 recent GNB blood isolates from CP were tested using CLSI approved methods for MIC determination by broth microdilution. Comparator agents were amikacin (A), aztreonam (AZ), ceftazidime (CZ), ceftazidime/avibactam (CAV), cefepime (CEF), ciprofloxacin (CIP), colistin (CL), meropenem (MR), ceftolozane/tazobactam (C/T), tigecycline (TG), and trimethoprim/sulfamethoxazole (T/S). Results CFDC MIC90s as mg/L were: S. maltophilia [50 isolates] 0.25, E. coli (ESBL−) [50 isolates] 0.5, E. coli (ESBL+) [51 isolates] 2.0, K. pneumoniae (ESBL− and +) [60 isolates] 0.5; K. pneumoniae (CRE) [22 isolates] 2.0; P. aeruginosa (MDR) [32 isolates] 1.0; E. cloacae [27 isolates] 4.0; Achromobacter spp. [15 isolates] 0.12. CFDC inhibited P. agglomerans, Burkholderia spp., Sphingomonas spp., Ochrobactrum spp. at ≤1 mg/L [23 total isolates] and Elizabethkingia spp. and R. radiobacter at ≤8 mg/L [11 total isolates]. Among comparator agents, only T/S had consistent activity against S. maltophilia. For E. coli (ESBL− and +) MR, TG, CAV, CL were most active. For K. pneumoniae (ESBL–and +) MR, CAV were most active. For K. pneumoniae (CRE) and P. aeruginosa (MDR), none of the comparators had significant activity. For E. cloacae, MR, A, CAV, TG were most active. Among the uncommon organisms, MR and TG had the greatest activity. Conclusion Although susceptibility breakpoints have yet to be determined, CFDC has significant activity (≤4 mg/L) against most problematic Gram-negative organisms causing infections in CP based on available pharmacokinetic/pharmacodynamic data. In particular, its activity against S. maltophilia was superior to the comparators. Also, it was the most active agent against P. aeruginosa (MDR) and K. pneumoniae (CRE). Based on our results, CFDC warrants clinical evaluation for the treatment of blood stream infections caused by GNB in CP. Disclosures K. V. I. Rolston, Merck: Investigator, Research grant; JMI Laboratories: Investigator, Research grant; Shionogi (Japan): Investigator, Research grant. B. Gerges, Shionogi: Collaborator, Research support. S. L. Aitken, Shionogi: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Medicines Co: Scientific Advisor, Consulting fee; Achaogen: Scientific Advisor, Consulting fee; Zavante: Scientific Advisor, Consulting fee; R. Prince, Shionogi: Investigator, Research support. Merck: Investigator, Research support.

scholarly journals In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Panel Strains

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 267 ◽  
Author(s):  
Le Phuong Nguyen ◽  
Naina Adren Pinto ◽  
Thao Nguyen Vu ◽  
Hyunsook Lee ◽  
Young Lag Cho ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Vitro Activity ◽  
Intrinsic Activity ◽  
In Vitro Activity ◽  
E Coli ◽  
Acinetobacter Spp ◽  
Resistant Strains ◽  
Lactamase Inhibitor

This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-β-lactam β-lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. isolates. GT-1 and GT-1/GT-055 were tested in vitro against comparators among three different characterised panel strain sets. Bacterial resistome and siderophore uptake systems were characterised to elucidate the genetic basis for GT-1 minimum inhibitory concentrations (MICs). GT-1 exhibited in vitro activity (≤2 μg/mL MICs) against many MDR isolates, including extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing E. coli and K. pneumoniae and oxacillinase (OXA)-producing Acinetobacter spp. GT-1 also inhibited strains with mutated siderophore transporters and porins. Although BLI GT-055 exhibited intrinsic activity (MIC 2–8 μg/mL) against most E. coli and K. pneumoniae isolates, GT-055 enhanced the activity of GT-1 against many GT-1–resistant strains. Compared with CAZ-AVI, GT-1/GT-055 exhibited lower MICs against E. coli and K. pneumoniae isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of E. coli, K. pneumoniae and Acinetobacter spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1–resistant strains.

scholarly journals In Vivo Modulation of a DnaJ Homolog, CbpA, by CbpM

2007 ◽  
Vol 189 (9) ◽  
pp. 3635-3638 ◽  
Author(s):  
Matthew R. Chenoweth ◽  
Nancy Trun ◽  
Sue Wickner
Keyword(s):  
Escherichia Coli ◽  
Cell Growth ◽  
Stationary Phase ◽  
Specific Inhibitor ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
E Coli ◽  
Hsp70 Chaperone

ABSTRACT CbpA, an Escherichia coli DnaJ homolog, can function as a cochaperone for the DnaK/Hsp70 chaperone system, and its in vitro activity can be modulated by CbpM. We discovered that CbpM specifically inhibits the in vivo activity of CbpA, preventing it from functioning in cell growth and division. Furthermore, we have shown that CbpM interacts with CbpA in vivo during stationary phase, suggesting that the inhibition of activity is a result of the interaction. These results reveal that the activity of the E. coli DnaK system can be regulated in vivo by a specific inhibitor.

In vitro activity of water-soluble quaternary chitosan chloride salt against E. coli

2010 ◽  
Vol 26 (11) ◽  
pp. 2089-2092 ◽  
Author(s):  
Leandro Prezotto da Silva ◽  
Douglas de Britto ◽  
Mirna Helena Regali Seleghim ◽  
Odilio B. G. Assis
Keyword(s):  
Water Soluble ◽  
Vitro Activity ◽  
Chloride Salt ◽  
In Vitro Activity ◽  
E Coli

scholarly journals 728. Activity of Eravacycline Against Contemporary Gram-Negative Clinical Isolates From New York City Hospitals

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S326-S326
Author(s):  
Alejandro Iregui ◽  
Zeb Khan ◽  
David Landman ◽  
John M Quale
Keyword(s):  
New York ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
E Coli ◽  
The Usa ◽  
Recent Collection

Abstract Background Antibiotic-resistant Gram-negative bacteria, including KPC-producing Enterobacteriaceae and carbapenem-resistant A. baumannii, have been problematic hospital pathogens in NYC and other areas. Eravacycline (ERV), a fluorocycline antibiotic released in the USA in 2018, has demonstrated in vitro activity against many of these strains. We tested the activity of ERV against a recent collection of clinical isolates from NYC hospitals. Methods For a 3-month period in 2017, all unique patient isolates of E. coli, K. pneumoniae, Enterobacter spp., and A. baumannii were collected from 7 hospitals in Brooklyn, NY. MICs were performed by broth microdilution for ERV and Tigecycline (TGC) and agar dilution for other antibiotics according to CLSI methodology. Cephalosporin-resistant isolates were screened by PCR for common carbapenemases. Results The susceptibility results for tetracycline and ERV are listed in the Table. Overall, 95% of the Enterobacteriaceae were inhibited by ≤ 0.5 μg/mL of ERV, the FDA-suggested breakpoint. Of 1,876 isolates of E. coli, 4 possessed KPC. ERV MICs for these 4 isolates were 0.125–0.25 μg/mL. Of 518 isolates of K. pneumoniae, 20 possessed KPC. The ERV MIC50 and MIC90 for these isolates were 1 and 1 μg/mL, respectively. Of 172 isolates of Enterobacter spp., 3 possessed KPC. ERV MICs for these 3 isolates were 0.5–1 μg/mL. Of 45 isolates of A. baumannii, 11 isolates possessed a carbapenemase (OXA23 in 8, OXA24 in 2, and KPC in 1). The ERV MIC50 and MIC90 for these isolates were 1 and 2 μg/mL, respectively. Overall, ERV MICs were two-fold lower than TGC MICs for A. baumannii. Conclusion ERV possesses significant in vitro activity against contemporary clinical isolates of Enterobacteriaceae and A. baumannii from NYC, including many carbapenemase producing strains. Disclosures All authors: No reported disclosures.

scholarly journals 1378. Evaluation of the In vitro Activity of Meropenem-Vaborbactam Against Carbapenem-Resistant Enterobacteriaceae, Including Isolates Resistant to Ceftazidime–Avibactam

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S422-S422
Author(s):  
William R Wilson ◽  
Ellen Kline ◽  
Chelsea Jones ◽  
Kristin Morder ◽  
Cornelius J Clancy ◽  
...  
Keyword(s):  
Premature Stop Codon ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Wild Type ◽  
In Vitro Susceptibility ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Research Grant

Abstract Background Meropenem-vaborbactam (M-V) is a novel antibiotic for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections. Our objective was to determine the in vitro activity of meropenem-vaborbactam against genetically-diverse CRE isolates, including those that have developed resistance to Ceftazidime–Avibactam (C-A). Methods Minimum inhibitory concentrations (MICs) were determined for meropenem (MER), M-V, and C-A by reference broth microdilution (BMD) methods in triplicate. Vaborbactam and avibactam were tested at fixed concentrations of 8 and 4 µg/mL, respectively. Quality control strains were used and within expected ranges. Polymerase chain reaction (PCR) with DNA sequencing was used to detect resistance determinants, including Klebsiella pneumoniae carbapenemase (KPC) subtypes and porin mutations. Results A total of 117 CRE isolates were tested, including K. pneumoniae (Kp; n = 83), E. cloacae (n = 17), E. coli (n = 10), and E. aerogenes (n = 7). Seventy-nine percent harbored blaKPC. KPC subtypes included KPC-2 (n = 32), KPC-3 (n = 41), KPC-3 variants (n = 16), and KPC [not typed] (n = 4, all E. coli). Among 74 K. pneumoniae, 95% had a premature stop codon in ompk35 and ompK36 genotypes included wild type (n = 48), IS5 insertion (n = 13), 135–136 DG duplication (n = 9), and other mutations (n = 4). The median (range) MICs for MER, C-A, and M-V were 8 (0.06 to ≥128), 1 (0.25 to ≥512), and 0.03 (0.015––16), respectively. Corresponding rates of susceptibility were 23, 84, and 98%, respectively. Fifty-three percent and 95% of C-A-resistant isolates were susceptible to MER and M-V, respectively. Among Kp, C-A MICs did not vary by KPC subtype or porin genotype. On the other hand, median M-V MICs were higher among KPC-2 than KPC-3 Kp (0.12 vs. 0.03; P = 0.002), and among Kp with ompK36 porin mutations compared with wild type (0.25 vs. 0.03; P < 0.001). Among Kp with KPC-3 variants (n = 16), the median M-V MIC was 0.03 (0.015––2); 100% were M-V susceptible. Median M-V MICs did not vary by CRE species. Only two isolates were M-V resistant, both were E. cloacae that did not harbor blaKPC. Conclusion M-V demonstrates high rates of in vitro susceptibility against diverse CRE isolates, including those that are resistant to C-A. As this agent is introduced into the clinic, it will be important to identify K. pneumoniae isolates harboring KPC-2 with ompK36 porin mutations that demonstrate higher MICs. Disclosures M. H. Nguyen, Merck: Grant Investigator, Research grant. Astellas: Grant Investigator, Research grant.

scholarly journals 714. Analysis of the Effect of Urine on the In Vitro Activity of Gepotidacin and Levofloxacin Against Escherichia coli, Staphylococcus epidermidis, and Staphylococcus saprophyticus

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S321-S321
Author(s):  
Laura M Koeth ◽  
Jeanna M DiFranco-Fisher ◽  
Nicole Scangarella-Oman
Keyword(s):  
Reference Method ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Urine Ph ◽  
Topoisomerase Iv ◽  
Acute Cystitis ◽  
E Coli ◽  
Microdilution Method ◽  
Broth Microdilution Method

Abstract Background Gepotidacin (GSK2140944) is a first in class novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in clinical development for the treatment of gonorrhea and uncomplicated UTI (acute cystitis). Gepotidacin selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechanism not utilized by any currently approved therapeutic agent and demonstrates in vitro activity against most target pathogens resistant to established antibacterials, including fluoroquinolones. This study was undertaken to determine the effect of various urine parameters on the in vitro activity of gepotidacin and a comparative agent, levofloxacin, against a variety of bacteria. Methods Study strains were tested according to the reference CLSI broth microdilution method using cation-adjusted Mueller–Hinton broth (CAMHB) and the following method variations: CAMHB with 25%, 50%, and 100% urine (not pH adjusted) and 100% urine (pH adjusted to 7.2–7.4, and 8). Quality control strains were concurrently tested each day. Results MIC endpoints in the reference method and in 100% urine were easily determined (i.e., clear buttons of growth up to the first well of no growth). Gepotidacin MIC results are summarized in the table. For E. coli and S. saprophyticus, there was a trend for higher gepotidacin MIC results with the addition of increasing amounts of urine. However, the increase was minimal such that mean dilution differences were ≤ 1.54. Against S. epidermidis, gepotidacin MICs were not significantly impacted by the addition of urine as 100% of urine condition MICs were within ±1 doubling dilution of the reference method MIC. The gepotidacin results for E. coli indicate that the average 1–2 dilution MIC increase observed in the unadjusted 100% pooled urine MIC may be associated with lower pH. A similar increase in levofloxacin MIC results for E. coli were also associated with pH, but at the higher pH of 8.0. In contrast, the increase in MIC observed in both the gepotidacin and levofloxacin S. saprophyticus results in 100% pooled urine do not appear to be a function of pH. Conclusion Overall, the effect of urine on the gepotidacin and levofloxacin MICs was minimal and not inclusive of all strains tested. Disclosures All authors: No reported disclosures.

scholarly journals In Vitro Activity of a Novel Siderophore-Cephalosporin LCB10-0200 (GT-1), and LCB10-0200/Avibactam, against Carbapenem-Resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa Strains at a Tertiary Hospital in Korea

2021 ◽  
Vol 14 (4) ◽  
pp. 370
Author(s):  
Le Phuong Nguyen ◽  
Chul Soon Park ◽  
Naina Adren Pinto ◽  
Hyunsook Lee ◽  
Hyun Soo Seo ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Strong Activity ◽  
E Coli ◽  
Carbapenem Resistant

The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB10-0200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB10-0200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC- producing E. coli and K. pneumoniae, while LCB10-0200 alone was active against ADC-, OXA-, and VIM- producing A. baumannii and P. aeruginosa. Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP- and NDM- producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli, K. pneumoniae.

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