scholarly journals Emerging ceftazidime-avibactam resistance against carbapenem resistant Escherichia coli and Klebsiella pneumoniae in Lebanon

10.3823/858 ◽  
2021 ◽  
Author(s):  
Ghena M Sobh ◽  
Abdul Karim El Karaaoui ◽  
Mira El Chaar ◽  
George F Araj
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistant ◽  
Novel Drug ◽  
Vitro Data ◽  
In Vitro Data ◽  
Carbapenem Resistant Enterobacteriaceae

Ceftazidime-avibactam (CZA) has been introduced as a novel drug to essentially combat the rising trends of carbapenem resistant Enterobacteriaceae. In the absence of in vitro data about the activity of this drug against carbapenem resistant (CR) Escherichia coli and Klebsiella pneumoniae in Lebanon, this study was warranted.

scholarly journals In VitroandIn VivoActivities of Tigecycline-Colistin Combination Therapies against Carbapenem-Resistant Enterobacteriaceae

2014 ◽  
Vol 58 (6) ◽  
pp. 3541-3546 ◽  
Author(s):  
Jonathan W. Betts ◽  
Lynette M. Phee ◽  
Michael Hornsey ◽  
Neil Woodford ◽  
David W. Wareham
Keyword(s):  
Escherichia Coli ◽  
Animal Model ◽  
Klebsiella Pneumoniae ◽  
Galleria Mellonella ◽  
Combination Therapies ◽  
Viable Option ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACTWe assessed the activity of tigecycline (TGC) combined with colistin (COL) against carbapenem-resistant enterobacteria. Synergy occurredin vitroagainst the majority of isolates, with the exception ofSerratia marcescens. In a simple animal model (Galleria mellonella), TGC-COL was superior (P< 0.01) in treatingEscherichia coli,Klebsiella pneumoniae, andEnterobacterinfections, including those with TGC-COL resistance. Clinical studies are needed to determine whether TGC-COL regimens may be a viable option.

scholarly journals Unusual Escherichia coli PBP 3 Insertion Sequence Identified from a Collection of Carbapenem-Resistant Enterobacteriaceae Tested In Vitro with a Combination of Ceftazidime-, Ceftaroline-, or Aztreonam-Avibactam

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Yunliang Zhang ◽  
Ankita Kashikar ◽  
C. Adam Brown ◽  
Gerald Denys ◽  
Karen Bush
Keyword(s):  
Escherichia Coli ◽  
Health Care ◽  
Gene Duplication ◽  
Insertion Sequence ◽  
Penicillin Binding Protein ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Health Care Centers ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Carbapenemase-producing Enterobacteriaceae isolates (n = 110) from health care centers in central Indiana (from 2010 to 2013) were tested for susceptibility to combinations of avibactam (4 μg/ml) with ceftazidime, ceftaroline, or aztreonam. MIC50/MIC90 values were 1/2 μg/ml (ceftazidime-avibactam), 0.5/2 μg/ml (ceftaroline-avibactam), and 0.25/0.5 μg/ml (aztreonam-avibactam.) A β-lactam MIC of 8 μg/ml was reported for the three combinations against one Escherichia coli isolate with an unusual TIPY insertion following Tyr344 in penicillin-binding protein 3 (PBP 3) as the result of gene duplication.

scholarly journals Detection of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae producing NDM-1 in Lebanon

2012 ◽  
Vol 6 (05) ◽  
pp. 457-461 ◽  
Author(s):  
Rima I El-Herte ◽  
George F Araj ◽  
Ghassan M Matar ◽  
Maysa Baroud ◽  
Zeina A Kanafani ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
New Delhi ◽  
Beta Lactamase ◽  
The Novel ◽  
First Report ◽  
Carbapenem Resistant ◽  
Lactamase Gene ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem resistance has been encountered globally with poor outcome of infected patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have emerged and are now spreading in all continents. This is the first report of Iraqi patients referred to Lebanon from whom carbapenem resistant Enterobacteriaceae were recovered. The genes involved in carbapenem resistance were bla-OXA-48   and the novel NDM-1. This report highlights the alarming introduction of such resistance among Enterobacteriaecae to this country.

scholarly journals KPC-mediated resistance to ceftazidime-avibactam and collateral effects in Klebsiella pneumoniae

2021 ◽  
Author(s):  
Jacqueline Findlay ◽  
Laurent Poirel ◽  
Mario Juhas ◽  
Patrice Nordmann
Keyword(s):  
Klebsiella Pneumoniae ◽  
Broad Spectrum ◽  
In Vitro Selection ◽  
Multidrug Resistant ◽  
Single Step ◽  
Carbapenem Resistant ◽  
Rapid Spread ◽  
Collateral Effects ◽  
Novel Drug

Carbapenem-resistant Enterobacterales, such as KPC-producing Klebsiella pneumoniae , represent a major threat to public health due to their rapid spread. Novel drug combinations such as ceftazidime-avibactam (CZA), combining a broad-spectrum cephalosporin along with a broad-spectrum ß-lactamase inhibitor, have recently been introduced and have been shown to exhibit excellent activity towards multidrug-resistant KPC-producing Enterobacterale strains. However, CZA-resistant K. pneumoniae isolates are now being increasingly reported, mostly corresponding to producers of KPC variants. In this study, we evaluated in vitro the nature of the mutations in the KPC-2 and KPC-3 ß-lactamase sequences (the most frequent KPC-type enzymes) that lead to CZA resistance, and the subsequent effects of these mutations on susceptibility to other ß-lactam antibiotics. Single-step in vitro selection assays were conducted resulting in the identification of a series of mutations in the KPC sequence which conferred the ability to those mutated enzymes to confer resistance to CZA. Hence, 16 KPC-2 variants and 10 KPC-3 variants were obtained. Production of the KPC variants in an Escherichia coli recombinant strain resulted in a concomitant increased susceptibility to broad-spectrum cephalosporins and carbapenems, with the exceptions of ceftazidime and piperacillin-tazobactam, compared to wild-type KPC enzymes. Enzymatic assays showed that all of the KPC variants identified exhibited an increased affinity toward ceftazidime and a slightly decreased sensitivity to avibactam, sustaining their impact on CZA resistance. However their respective carbapenemase activities were concurrently negatively impacted.

scholarly journals Appropriate Treatment for Bloodstream Infections Due to Carbapenem-Resistant Klebsiella pneumoniae and Escherichia coli: A Nationwide Multicenter Study in Taiwan

2018 ◽  
Vol 6 (2) ◽  
Author(s):  
Yi-Tsung Lin ◽  
Chin-Fang Su ◽  
Chien Chuang ◽  
Jung-Chung Lin ◽  
Po-Liang Lu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multivariate Analysis ◽  
Klebsiella Pneumoniae ◽  
Multicenter Study ◽  
Bloodstream Infections ◽  
Carbapenem Resistant ◽  
Appropriate Treatment ◽  
Comorbidity Index ◽  
Enterobacteriaceae Infections ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background In a multicenter study from Taiwan, we aimed to investigate the outcome of patients who received different antimicrobial therapy in carbapenem-resistant Enterobacteriaceae bloodstream infections and proposed a new definition for tigecycline use. Methods Patients from 16 hospitals in Taiwan who received appropriate therapy for bloodstream infections due to carbapenem-resistant Klebsiella pneumoniae and Escherichia coli were enrolled in the study between January 2012 and June 2015. We used a cox proportional regression model for multivariate analysis to identify independent risk factors of 14-day mortality. Tigecycline was defined as appropriate when the isolates had a minimum inhibitory concentration (MIC) ≤0.5 mg/L, and we investigated whether tigecycline was associated with mortality among patients with monotherapy. Results Sixty-four cases with carbapenem-resistant K pneumoniae (n = 50) and E coli (n = 14) bloodstream infections were analyzed. Of the 64 isolates, 17 (26.6%) had genes that encoded carbapenemases. The 14-day mortality of these cases was 31.3%. In the multivariate analysis, Charlson Comorbidity Index (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03–1.42; P = .022) and colistin monotherapy (HR, 5.57; 95% CI, 2.13–14.61; P &lt; .001) were independently associated with 14-day mortality. Among the 55 patients with monotherapy, the 14-day mortality was 30.9% (n = 17). Tigecycline use was not associated with mortality in the multivariate analysis. Conclusions Tigecycline monotherapy was a choice if the strains exhibited MIC ≤0.5 mg/L, and colistin monotherapy was not suitable. Our findings can initiate additional clinical studies regarding the efficacy of tigecycline in carbapenem-resistant Enterobacteriaceae infections.

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 In Vitro Synergism of Azithromycin Combination with Antibiotics against OXA-48-Producing Klebsiella pneumoniae Clinical Isolates

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1551
Author(s):  
Uthaibhorn Singkham-in ◽  
Netchanok Muhummudaree ◽  
Tanittha Chatsuwan
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
In Vitro Activity ◽  
Bacterial Regrowth ◽  
Antibiotic Development ◽  
Carbapenem Resistant

Carbapenem-resistant Klebsiella pneumoniae has globally emerged as an urgent threat leading to the limitation for treatment. K. pneumoniae carrying blaOXA-48, which plays a broad magnitude of carbapenem susceptibility, is widely concerned. This study aimed to characterize related carbapenem resistance mechanisms and forage for new antibiotic combinations to combat blaOXA-48-carrying K. pneumoniae. Among nine isolates, there were two major clones and a singleton identified by ERIC-PCR. Most isolates were resistant to ertapenem (MIC range: 2–>256 mg/L), but two isolates were susceptible to imipenem and meropenem (MIC range: 0.5–1 mg/L). All blaOXA-48-carrying plasmids conferred carbapenem resistance in Escherichia coli transformants. Two ertapenem-susceptible isolates carried both outer membrane proteins (OMPs), OmpK35 and OmpK36. Lack of at least an OMP was present in imipenem-resistant isolates. We evaluated the in vitro activity of an overlooked antibiotic, azithromycin, in combination with other antibiotics. Remarkably, azithromycin exhibited synergism with colistin and fosfomycin by 88.89% and 77.78%, respectively. Bacterial regrowth occurred after exposure to colistin or azithromycin alone. Interestingly, most isolates were killed, reaching synergism by this combination. In conclusion, the combination of azithromycin and colistin may be an alternative strategy in dealing with blaOXA-48-carrying K. pneumoniae infection during a recent shortage of newly effective antibiotic development.

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 1952. Bacteriophage Treatment Improves Survival of Mice Infected with Carbapenem-Resistant Klebsiella pneumoniae

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S60-S60
Author(s):  
Shayla Hesse ◽  
Natalia Malachowa ◽  
Adeline Porter ◽  
Brett Freedman ◽  
Scott Kobayashi ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Control Group ◽  
Lytic Phage ◽  
Mouse Blood ◽  
Carbapenem Resistant ◽  
In Vitro Data

Abstract Background Bacteriophage (phage) therapy is being considered as a treatment option for patients with multi-drug-resistant bacterial infections. However, there is a dearth of controlled clinical data to support therapeutic phage efficacy. As a first step toward addressing this deficiency, we tested the ability of two well-characterized phages, alone and in combination, to kill carbapenem-resistant Klebsiella pneumoniae (ST258) in blood in vitro and rescue mice from lethal ST258 infection. Methods Wild-type C57BL/6J mice were infected with a lethal inoculum of ST258 by intra-peritoneal (IP) injection followed 1 hour later by IP administration of lytic phage P1, P2, or P1+P2 at a multiplicity of infection (MOI) estimated at 1. Survival of each group of mice was tracked for 10 days. In separate experiments, mice were sacrificed at 1 hour, 24 hours, and 48 hours post-phage treatment. Mouse blood and tissues were collected at each timepoint for enumeration of bacteria and phage, screening for phage resistance, and histopathology. Results ST258 survival in mouse blood in vitro was significantly less after 1 hour of incubation with P1 or P1+P2 (MOI 1) compared with the control group (no phage). Consistent with the in vitro data, none of the mice (0/15) in the control group (no phage) survived to 10 days post-infection, whereas 12/15, 14/15, and 15/15 mice survived in the P2, P1, and P1+P2-treated groups, respectively (P < 0.0001). Conclusion Prompt, systemic administration of lytic bacteriophages rescued mice from lethal ST258 infection. These data support the potential of phage therapy to effectively treat infections caused by ST258. It will be important to assess whether, for other phage-bacteria combinations, in vitro lysis in blood correlates with in vivo treatment efficacy and therefore may have predictive utility. Disclosures All Authors: No reported Disclosures.

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