Characterization of carbapenem resistance mechanisms inKlebsiella pneumoniaeandin vitrosynergy of the colistin–meropenem combination

2014 ◽  
Vol 27 (5) ◽  
pp. 277-282 ◽  
Author(s):  
Lakshmana Gowda Krishnappa ◽  
Mohammed Ali M. Marie ◽  
Yazeed A. Al Sheikh
Keyword(s):  
Carbapenem Resistance ◽  
Resistance Mechanisms

scholarly journals Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  
Keyword(s):  
Lipid A ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Resistance Mechanisms ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

scholarly journals 480. Molecular Characterization of Multidrug-Resistant Gram-Negative Pathogens in Three Tertiary Care Hospitals in Egypt

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S235-S235
Author(s):  
Amani Kholy ◽  
Samia A Girgis ◽  
Arwa R Elmanakhly ◽  
Mervat A F Shetta ◽  
Dalia El- Kholy ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Resistance Genes ◽  
Genetic Basis ◽  
Tertiary Care ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Gram Negative ◽  
E Coli ◽  
Tertiary Care Hospitals

Abstract Background High rates of AMR among Gram-negative bacilli (GNB) have been reported from Egypt for almost 2 decades. Surveillance and identifying the genetic basis of AMR provide important information to optimize patient care. As there is no adequate data on the genetic basis of AMR in Egypt, we aimed to identify the molecular characterization of multi-drug-resistant (MDR) Gram-negative pathogens (GNP). Methods Three major tertiary-care hospitals in Egypt participated in the “Study for Monitoring Antimicrobial Resistance Trends” (SMART) from 2014 to 2016. Consecutive GNPs were identified and their susceptibility to antimicrobials were tested. Molecular identification of ESBL, AmpC, and carbapenemase resistance genes was conducted on MDR isolates. Results We enrolled 1,070 consecutive Gram-negative isolates; only one isolate per patient according to the standard protocol of (SMART). During 2014–2015, 578 GNP were studied. Enterobacteriaceae comprised 66% of the total isolates. K. pneumoniae and E. coli were the most common (29.8% and 29.4%). K. pneumoniae and E. coli were the predominant organisms in IAI (30.5% and 30.1%, respectively) and UTI (and 38.9% and 48.6%, respectively), while Acinetobacter baumannii was the most prevalent in RTI (40.2%). ESBL producers were phenotypically detected in 53% of K. pneumoniae, and 68% of E. coli. During 2016, 495 GNP were studied. ESBL continued to be high. For E. coli and K. pneunomiea, the most active antimicrobials were amikacin (≥93%), imipenem/meropenem (≥87%) and colistin (97%). Genetic study of ertapenem-resistant isolates and 50% of isolates with ESBL phenotype revealed ESβL production in more than 90% of isolates; blaCTXM-15 was detected in 71.4% and 68.5% in K. pneumoniae and E. coli, respectively, blaTEM-OSBL in 48.5% and47.5% of K. pneumoniae and E. coli, respectively. Carbapenem resistance genes were detected in 45.4% of isolates. In K. pneumoniae, OXA-48 dominated (40.6%), followed by NDM1 (23.7%) and OXA-232 (4.5%). Conclusion Our study detected alarming rates of resistance and identified many resistance mechanisms in clinical isolates from Egyptian hospitals. These high rates highlight the importance of continuous monitoring of the resistance trend and discovering the novel resistant mechanisms of resistance, and the underscores a national antimicrobial stewardship plan in Egypt. Disclosures All authors: No reported disclosures.

scholarly journals 4-Amino-2-Sulfanylbenzoic Acid as a Potent Subclass B3 Metallo-β-Lactamase-Specific Inhibitor Applicable for Distinguishing Metallo-β-Lactamase Subclasses

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Jun-ichi Wachino ◽  
Reo Kanechi ◽  
Erina Nishino ◽  
Marie Mochizuki ◽  
Wanchun Jin ◽  
...  
Keyword(s):  
Specific Inhibitor ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Health Concern ◽  
Conserved Residues ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Promising Strategy ◽  
Starting Point

ABSTRACT The number of cases of infection with carbapenem-resistant Enterobacteriaceae (CRE) has been increasing and has become a major clinical and public health concern. Production of metallo-β-lactamases (MBLs) is one of the principal carbapenem resistance mechanisms in CRE. Therefore, developing MBL inhibitors is a promising strategy to overcome the problems of carbapenem resistance conferred by MBLs. To date, the development and evaluation of MBL inhibitors have focused on subclass B1 MBLs but not on B3 MBLs. In the present study, we searched for B3 MBL (specifically, SMB-1) inhibitors and found thiosalicylic acid (TSA) to be a potent inhibitor of B3 SMB-1 MBL (50% inhibitory concentration [IC50], 0.95 μM). TSA inhibited the purified SMB-1 to a considerable degree but was not active against Escherichia coli cells producing SMB-1, as the meropenem (MEM) MIC for the SMB-1 producer was only slightly reduced with TSA. We then introduced a primary amine to TSA and synthesized 4-amino-2-sulfanylbenzoic acid (ASB), which substantially reduced the MEM MICs for SMB-1 producers. X-ray crystallographic analyses revealed that ASB binds to the two zinc ions, Ser221, and Thr223 at the active site of SMB-1. These are ubiquitously conserved residues across clinically relevant B3 MBLs. ASB also significantly inhibited other B3 MBLs, including AIM-1, LMB-1, and L1. Therefore, the characterization of ASB provides a starting point for the development of optimum B3 MBL inhibitors.

scholarly journals Carbapenem Resistance Mechanisms in Pseudomonas aeruginosa Clinical Isolates

2001 ◽  
Vol 45 (2) ◽  
pp. 480-484 ◽  
Author(s):  
Hyunjoo Pai ◽  
Jong-Won Kim ◽  
Jungmin Kim ◽  
Ji Hyang Lee ◽  
Kang Won Choe ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Efflux System ◽  
Clinical Strains ◽  
Carbapenem Resistant

ABSTRACT In order to define the contributions of the mechanisms for carbapenem resistance in clinical strains of Pseudomonas aeruginosa, we investigated the presence of OprD, the expressions of the MexAB-OprM and MexEF-OprN systems, and the production of the β-lactamases for 44 clinical strains. All of the carbapenem-resistant isolates showed the loss of or decreased levels of OprD. Three strains overexpressed the MexAB-OprM efflux system by carrying mutations inmexR. These three strains had the amino acid substitution in MexR protein, Arg (CGG) → Gln (CAG), at the position of amino acid 70. None of the isolates, however, expressed the MexEF-OprN efflux system. For the characterization of β-lactamases, at least 13 isolates were the depressed mutants, and 12 strains produced secondary β-lactamases. Based on the above resistance mechanisms, the MICs of carbapenem for the isolates were analyzed. The MICs of carbapenem were mostly determined by the expression of OprD. The MICs of meropenem were two- to four-fold increased for the isolates which overexpressed MexAB-OprM in the background of OprD loss. However, the elevated MICs of meropenem for some individual isolates could not be explained. These findings suggested that other resistance mechanisms would play a role in meropenem resistance in clinical isolates of P. aeruginosa.

scholarly journals Characterization of Porin Expression in Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae Identifies Isolates Most Susceptible to the Combination of Colistin and Carbapenems

2013 ◽  
Vol 57 (5) ◽  
pp. 2147-2153 ◽  
Author(s):  
Jae H. Hong ◽  
Cornelius J. Clancy ◽  
Shaoji Cheng ◽  
Ryan K. Shields ◽  
Liang Chen ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Bacterial Killing ◽  
Content Type ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Effective Combination ◽  
Time Kill ◽  
Combination Regimens

ABSTRACTWe characterized carbapenem resistance mechanisms among 12Klebsiella pneumoniaecarbapenemase (KPC)-producingK. pneumoniae(referred to here as KPCK. pneumoniae) clinical isolates and evaluated their effects on the activity of 2- and 3-drug combinations of colistin, doripenem, and ertapenem. All isolates were resistant to ertapenem and doripenem; 75% (9/12) were resistant to colistin. Isolates belonged to the ST258 clonal group and harboredblaKPC-2,blaSHV-12, andblaTEM-1. As determined by time-kill assays, doripenem (8 μg/ml) and ertapenem (2 μg/ml) were inactive against 92% (11/12) and 100% (12/12) of isolates, respectively. Colistin (2.5 μg/ml) exerted some activity (range, 0.39 to 2.5 log10) against 78% (7/9) of colistin-resistant isolates. Colistin-ertapenem, colistin-doripenem, and colistin-doripenem-ertapenem exhibited synergy against 42% (5/12), 50% (6/12), and 67% (8/12) of isolates, respectively. Expression ofompK35andompK36porins correlated with each other (R2= 0.80). Levels of porin expression did not correlate with colistin-doripenem or colistin-ertapenem synergy. However, synergy with colistin-doripenem-ertapenem was more likely against isolates with high porin expression than those with low expression (100% [8/8] versus 0% [0/4];P= 0.002). Moreover, bactericidal activity (area under the bacterial killing curve) against isolates with high porin expression was greater for colistin-doripenem-ertapenem than colistin-doripenem or colistin-ertapenem (P≤ 0.049). In conclusion, colistin-carbapenem combinations may provide optimal activity against KPCK. pneumoniae, including colistin-resistant isolates. Screening for porin expression may identify isolates that are most likely to respond to a triple combination of colistin-doripenem-ertapenem. In the future, molecular characterization of KPCK. pneumoniaeisolates may be a practical tool for identifying effective combination regimens.

scholarly journals Characterization of carbapenem resistance mechanisms and integrons in Pseudomonas aeruginosa strains from blood samples in a French hospital

2016 ◽  
Vol 65 (4) ◽  
pp. 311-319 ◽  
Author(s):  
Beatriz Rojo-Bezares ◽  
Laurent Cavalié ◽  
Damien Dubois ◽  
Eric Oswald ◽  
Carmen Torres ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Blood Samples ◽  
French Hospital

scholarly journals Current Trends in Non-Invasive Imaging of Interactions in the Liver Tumor Microenvironment Mediated by Tumor Metabolism

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3645
Author(s):  
Isabel Theresa Schobert ◽  
Lynn Jeanette Savic
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Tumor Metabolism ◽  
Resistance Mechanisms ◽  
Metabolic Reprogramming ◽  
Non Invasive

With the increasing understanding of resistance mechanisms mediated by the metabolic reprogramming in cancer cells, there is a growing clinical interest in imaging technologies that allow for the non-invasive characterization of tumor metabolism and the interactions of cancer cells with the tumor microenvironment (TME) mediated through tumor metabolism. Specifically, tumor glycolysis and subsequent tissue acidosis in the realms of the Warburg effect may promote an immunosuppressive TME, causing a substantial barrier to the clinical efficacy of numerous immuno-oncologic treatments. Thus, imaging the varying individual compositions of the TME may provide a more accurate characterization of the individual tumor. This approach can help to identify the most suitable therapy for each individual patient and design new targeted treatment strategies that disable resistance mechanisms in liver cancer. This review article focuses on non-invasive positron-emission tomography (PET)- and MR-based imaging techniques that aim to visualize the crosstalk between tumor cells and their microenvironment in liver cancer mediated by tumor metabolism.

scholarly journals Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Michael J. Satlin ◽  
Liang Chen ◽  
Gopi Patel ◽  
Angela Gomez-Simmonds ◽  
Gregory Weston ◽  
...  
Keyword(s):  
New York ◽  
Empirical Therapy ◽  
Carbapenem Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Rapid Diagnostics ◽  
Multicenter Studies ◽  
Content Type ◽  
Medical Centers ◽  
Carbapenem Resistant

ABSTRACT Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.

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