In vitro activity of carvacrol in combination with meropenem against carbapenem-resistant Klebsiella pneumoniae

2021 ◽  
Author(s):  
Elif Odabaş Köse
Keyword(s):  
Klebsiella Pneumoniae ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Carbapenem Resistant

scholarly journals 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S412-S413
Author(s):  
Michael R Jacobs ◽  
Caryn E Good ◽  
Ayman M Abdelhamed ◽  
Daniel D Rhoads ◽  
Kristine M Hujer ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Next Generation ◽  
Aminoglycoside Resistance ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Research Grant

Abstract Background Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multicenter consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. Methods Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem-resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases. Isolates were submitted by participating CRACKLE centers. Results Carbapenemases present in study isolates included KPC-2 (n = 323), KPC-3 (n = 364), KPC-4 (n = 2), OXA-48 like (n = 7), and NDM (n = 1). Plazomicin MICs ranged from ≤0.12 to >32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (figure). MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining eight isolates were >32 mg/L. Plazomicin MICs were related to specific carbapenemases present in isolates: of eight isolates with MICs >32 mg/L, seven contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active. Conclusion Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates. Disclosures M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. L. Connolly, Achaogen, Inc.: Consultant, Consulting fee. K. M. Krause, Achaogen: Employee, Salary. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee.

Comparison of in vitro activities of plazomicin and other aminoglycosides against clinical isolates of Klebsiella pneumoniae and Escherichia coli

2021 ◽  
Author(s):  
Gizem İnce ◽  
Hasan Cenk Mirza ◽  
Aylin Üsküdar Güçlü ◽  
Hale Gümüş ◽  
Çiğdem Erol ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Resistance Rate ◽  
Vitro Activity ◽  
Diffusion Method ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Gradient Diffusion ◽  
Susceptibility Rate

Abstract Objectives To compare the in vitro activity of plazomicin and two older aminoglycosides (gentamicin and amikacin) against 180 isolates of Escherichia coli and Klebsiella pneumoniae, including subsets of 60 non-ESBL-producing, 60 ESBL-producing and 60 carbapenem-resistant (46 carrying blaOXA-48, 11 carrying blaNDM and 3 carrying blaOXA-48 and blaNDM) strains. Methods MICs of plazomicin, gentamicin and amikacin were determined by a gradient diffusion method. Gentamicin and amikacin MICs were interpreted according to CLSI criteria and EUCAST breakpoint tables. Plazomicin MICs were interpreted using FDA-defined breakpoints. Results All non-ESBL-producing and ESBL-producing isolates were susceptible to plazomicin. The plazomicin susceptibility rate (71.7%) in carbapenem-resistant isolates was significantly higher than those observed for gentamicin (45%) and amikacin (56.7% and 51.7% according to CLSI and EUCAST breakpoints, respectively). Gentamicin, amikacin and plazomicin susceptibility rates (35.6% for gentamicin; 44.4% and 37.8% for amikacin according to CLSI and EUCAST breakpoints, respectively; 64.4% for plazomicin) in carbapenem-resistant K. pneumoniae were significantly lower than those observed for carbapenem-resistant E. coli isolates (73.3% for gentamicin; 93.3% for amikacin and plazomicin). Gentamicin, amikacin and plazomicin susceptibility rates for blaNDM-positive isolates were lower than those observed for blaOXA-48-positive isolates, but differences were not statistically significant. Among the isolates that were non-susceptible to both gentamicin and amikacin, the plazomicin susceptibility rate was less than 30%. Conclusions Although plazomicin showed excellent in vitro activity against carbapenem-susceptible isolates, the plazomicin resistance rate increased to 35.6% among carbapenem-resistant K. pneumoniae and further increased to 45.5% among blaNDM-positive isolates.

scholarly journals 1265. In Vitro Activity of Aztreonam-Avibactam against Klebsiella pneumoniae Isolates Analyzed by Epidemic Lineage and Hypervirulence Factors Collected in China as Part of the ATLAS Global Surveillance Study in 2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S721-S721
Author(s):  
Mark Estabrook ◽  
Krystyna Kazmierczak ◽  
Francis Arhin ◽  
Daniel F Sahm
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Study ◽  
In Vitro Activity ◽  
Independent Contractor ◽  
Illumina Hiseq ◽  
Carbapenem Resistant ◽  
Class D

Abstract Background Hypervirulent Klebsiella pneumoniae (hvKp), unlike classical K. pneumoniae (cKp), are often responsible for community-acquired infections in otherwise healthy individuals. The acquisition of hypervirulence genes by sequence type 11 (ST11) carbapenem-resistant (CR) Kp endemic in Asia is a grave threat. Aztreonam-avibactam (ATM-AVI) is a monobactam combined with a β-lactamase inhibitor for the treatment of infections caused by Enterobacterales isolates that carry Class A, B, C and some Class D β-lactamases. Methods 487 K. pneumoniae isolates were collected from 17 sites in China in 2019 as a part of the ATLAS global surveillance study. 220 isolates with MICs >1 µg/ml to meropenem (MEM), ceftazidime or ATM were selected for whole genome sequencing (Illumina Hiseq 2x150 bp reads). Analyses were carried out using the CLC Genomics Workbench (Qiagen). Presence of the aerobactin synthesis locus differentiated hvKp and cKp. Antimicrobial susceptibility was determined by CLSI broth microdilution. Results Of the 487 isolates, MIC90 values for ATM-AVI (0.5 µg/ml; Table) were lower than those for any comparator tested, with only two isolates testing with MIC >4 µg/ml. Of the isolates sequenced, 82/220 (37.3%) were ST11. 53/82 (64.6%) of these ST11 isolates were hvKp (ATM-AVI, MIC90 1 µg/ml; range, 0.25-4 µg/ml) and showed percentages of susceptibility < 90% to three last-line agents (0% MEM-susceptible (S); 18.9% amikacin (AMK)-S; 88.7% tigecycline (TGC)-S). Isolates of other STs (Non-ST11) were less frequently identified as hvKp (24/138, 17.4%) and more Non-ST-11 hvKp and cKp alike were S to MEM and AMK relative to isolates of ST11 (75.0-86.8% MEM-S; 83.3-96.5% AMK-S). Likewise, the ATM-AVI MIC90 value (0.25 µg/ml) was 4-fold lower for Non-ST11 isolates. Results Table Conclusion CR ST11 hvKp represented at least 10.9% of the collected Kp isolates. ATM-AVI retained potent in vitro activity against these isolates which displayed resistance to a range of last-line agents. CST and TGC also displayed some activity but are limited in utility due to nephrotoxicity and poor accumulation in blood, respectively. The spread of virulence factors leading to the complicated clinical presentation of hvKp infection into multidrug-resistant lineages warrants continued surveillance. Disclosures Mark Estabrook, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

scholarly journals In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial

2021 ◽  
Author(s):  
Adam G. Stewart ◽  
Kyra Cottrell ◽  
Andrew Henderson ◽  
Kanthi Vemuri ◽  
Michelle J. Bauer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Severe Infection ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Carbapenem Resistant

Carbapenem antibiotics remain the treatment of choice for severe infection due to ESBL- and AmpC-producing Enterobacterales . The use of carbapenems is a major driver of the emergence of carbapenem-resistant Gram-negative bacilli, which are often resistant to most available antimicrobials.

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.

scholarly journals In vitro Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates

2020 ◽  
Vol 11 ◽  
Author(s):  
Mingju Hao ◽  
Xiaohong Shi ◽  
Jingnan Lv ◽  
Siqiang Niu ◽  
Shiqing Cheng ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Carbapenem Resistant
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