scholarly journals Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Ghady Haidar ◽  
Cornelius J. Clancy ◽  
Ryan K. Shields ◽  
Binghua Hao ◽  
Shaoji Cheng ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Content Type ◽  
Extended Spectrum

ABSTRACT We identified four bla KPC-3 mutations in ceftazidime-avibactam-resistant clinical Klebsiella pneumoniae isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165-166 KPC-3 variants. Using site-directed mutagenesis and transforming vectors into Escherichia coli, we conclusively demonstrated that mutant bla KPC-3 encoded enzymes that functioned as extended-spectrum β-lactamases; mutations directly conferred higher MICs of ceftazidime-avibactam and decreased the MICs of carbapenems and other β-lactams. Impact was strongest for the D179Y mutant, highlighting the importance of the KPC Ω-loop.

scholarly journals Carbapenem Therapy for Bacteremia Due to Extended-Spectrum-β-Lactamase-Producing Escherichia coli or Klebsiella pneumoniae: Implications of Ertapenem Susceptibility

2012 ◽  
Vol 56 (6) ◽  
pp. 2888-2893 ◽  
Author(s):  
Nan-Yao Lee ◽  
Ching-Chi Lee ◽  
Wei-Han Huang ◽  
Ko-Chung Tsui ◽  
Po-Ren Hsueh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Content Type ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Medical Centers ◽  
Extended Spectrum ◽  
Appropriate Therapy ◽  
Related Mortality

ABSTRACTA retrospective study was conducted at two medical centers in Taiwan to evaluate the clinical characteristics, outcomes, and risk factors for mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum-beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producingEscherichia coliandKlebsiella pneumoniaeisolates treated by a carbapenem were identified. Among these ESBL-producing isolates, rates of susceptibility to ertapenem (MICs ≤ 0.25 μg/ml) were 83.8% and 76.4%, respectively; those to meropenem were 100% and 99.3%, respectively; and those to imipenem were 100% and 97.9%, respectively. There were no significant differences in the critical illness rate (P= 0.1) or sepsis-related mortality rate (P= 0.2) for patients with bacteremia caused by ESBL-producingK. pneumoniae(140 isolates, 55.8%) andE. coli(111 isolates, 44.2%). Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84 to 43.34;P< 0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42 to 15.24;P= 0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04 to 12.88;P= 0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P= 0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs ≤ 0.25 μg/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs > 0.25 μg/ml), if treated by a carbapenem. However, the mortality for patients with bacteremic episodes due to isolates with MICs of ≤0.5 μg/ml was similar to the mortality for those whose isolates had MICs of >0.5 μg/ml (P= 0.8). Such a finding supports the rationale of the current CLSI 2011 criteria for carbapenems forEnterobacteriaceae.

scholarly journals Escherichia coli and Klebsiella pneumoniae Producing CTX-M Cephalosporinase from Swine Finishing Barns and Their Association with Antimicrobial Use

2012 ◽  
Vol 79 (3) ◽  
pp. 1052-1054 ◽  
Author(s):  
Dixie F. Mollenkopf ◽  
Jennifer M. Mirecki ◽  
Joshua B. Daniels ◽  
Julie A. Funk ◽  
Steven C. Henry ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Antimicrobial Use ◽  
Fecal Samples ◽  
Content Type ◽  
Extended Spectrum ◽  
Lactamase Gene

ABSTRACTWe report the recovery ofEscherichia coliorKlebsiella pneumoniaecontaining the extended-spectrum β-lactamase geneblaCTX-Mfrom 24 of 1,495 (1.6%) swine fecal samples in 8 of 50 (16%) finishing barns located in 5 U.S. states. We did not detect an association between antimicrobial use and recovery ofblaCTX-M.

scholarly journals Tigecycline DisplaysIn VivoBactericidal Activity against Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae after 72-Hour Exposure Period

2012 ◽  
Vol 57 (1) ◽  
pp. 640-642 ◽  
Author(s):  
Pamela R. Tessier ◽  
David P. Nicolau
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Clinical Outcomes ◽  
Bactericidal Activity ◽  
Exposure Period ◽  
Content Type ◽  
Density Reduction ◽  
Extended Spectrum ◽  
Level Of Activity

ABSTRACTProgressively enhanced activity of a humanized tigecycline (TGC) regimen was noted over 3 days against an extended-spectrum-β-lactamase (ESBL)-producingEscherichia coliisolate and an ESBL-producingKlebsiella pneumoniaeisolate. Bacterial density reduction approximated 3 log10approaching bactericidal activity at 72 h. This level of activity has not been previously noted for compounds such as tetracyclines, normally considered bacteriostatic antimicrobials. Extended regimen studiesin vivomay aid in better delineation of antimicrobial effects, producing improved correlation with clinical outcomes.

scholarly journals VIM-19, a Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli and Klebsiella pneumoniae

2009 ◽  
Vol 54 (1) ◽  
pp. 471-476 ◽  
Author(s):  
Jose-Manuel Rodriguez-Martinez ◽  
Patrice Nordmann ◽  
Nicolas Fortineau ◽  
Laurent Poirel
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Hydrolytic Activity ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Amino Acid Substitutions ◽  
Class 1 Integron ◽  
Carbapenem Resistant ◽  
Class 1

ABSTRACT Two carbapenem-resistant isolates, one Escherichia coli isolate and one Klebsiella pneumoniae isolate, recovered from an Algerian patient expressed a novel VIM-type metallo-β-lactamase (MBL). The identified bla VIM-19 gene was located on a ca. 160-kb plasmid and located inside a class 1 integron in both isolates. VIM-19 differed from VIM-1 by the Asn215Lys and Ser228Arg substitutions, increasing its hydrolytic activity toward carbapenems. Site-directed mutagenesis experiments showed that both substitutions were necessary for the increased carbapenemase activity of VIM-19. This study indicates that MBLs with enhanced activity toward carbapenems may be obtained as a result of very few amino acid substitutions.

scholarly journals Decreased Susceptibility to Noncarbapenem Antimicrobials in Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates in Toronto, Canada

2012 ◽  
Vol 56 (7) ◽  
pp. 3977-3980 ◽  
Author(s):  
Christopher F. Lowe ◽  
Allison McGeer ◽  
Matthew P. Muller ◽  
Kevin Katz
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Retrospective Review ◽  
Content Type ◽  
E Coli ◽  
Extended Spectrum ◽  
Susceptibility Profiles

ABSTRACTRetrospective review from 11 Canadian hospitals showed increasing incidence of extended-spectrum β-lactamase (ESBL)-producingEscherichia coliandKlebsiella pneumoniaefrom 0.12 per 1,000 inpatient days during 2005 to 0.47 per 1,000 inpatient days during 2009. By 2009, susceptibility rates of ESBL-positiveE. coli/K. pneumoniaewere as follows: ciprofloxacin, 12.8%/9.0%; TMP/SMX, 32.9%/12.2%; and nitrofurantoin, 83.8%/10.3%. Nosocomial and nonnosocomial ESBL-producingE. coliisolates had similar susceptibility profiles, while nonnosocomial ESBL-producingK. pneumoniaewas associated with decreased ciprofloxacin (P= 0.03) and nitrofurantoin (P< 0.001) susceptibilities.

scholarly journals Changing Epidemiology of Extended-Spectrum β-Lactamases in Argentina: Emergence of CTX-M-15

2012 ◽  
Vol 56 (11) ◽  
pp. 6003-6005 ◽  
Author(s):  
S. Sennati ◽  
G. Santella ◽  
J. Di Conza ◽  
L. Pallecchi ◽  
M. Pino ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Molecular Epidemiology ◽  
Content Type ◽  
Extended Spectrum ◽  
Multicenter Survey

ABSTRACTA multicenter survey, carried out in 2010 in Argentina, showed an increased prevalence of extended-spectrum β-lactamase (ESBL)-producing enterobacteria, with some changes in the molecular epidemiology of circulating ESBLs. While enzymes of the CTX-M-2 group remain endemic, the emergence of CTX-M-15 and of enzymes of the CTX-M-8 and CTX-M-9 groups was observed. The CTX-M-15-positive isolates represented 40% of CTX-M producers and included representatives ofEscherichia coliST131 andKlebsiella pneumoniaeST11.

scholarly journals Severe Sepsis Facilitates Intestinal Colonization by Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae and Transfer of the SHV-18 Resistance Gene to Escherichia coli during Antimicrobial Treatment

2013 ◽  
Vol 58 (2) ◽  
pp. 1039-1046 ◽  
Author(s):  
Jun Guan ◽  
Shaoze Liu ◽  
Zhaofen Lin ◽  
Wenfang Li ◽  
Xuefeng Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Severe Sepsis ◽  
Klebsiella Pneumoniae ◽  
Resistance Gene ◽  
Antimicrobial Treatment ◽  
Intestinal Colonization ◽  
Content Type ◽  
Challenge Strain ◽  
Gut Colonization ◽  
Extended Spectrum

ABSTRACTInfections caused by multidrug-resistant pathogens are frequent and life threatening in critically ill patients. To investigate whether severe sepsis affects gut colonization by resistant pathogens and genetic exchange between opportunistic pathogens, we tested the intestinal-colonization ability of an extended-spectrum beta-lactamase-producingKlebsiella pneumoniaestrain carrying the SHV-18 resistance gene and the transfer ability of the resistance gene to endogenousEscherichia coliunder ceftriaxone treatment in rats with burn injury only or severe sepsis induced by burns plus endotoxin exposure. Without ceftriaxone treatment, theK. pneumoniaestrain colonized the intestine in both septic and burned rats for a short time, with clearance occurring earlier in burn-only rats but never in sham burn rats. In both burned and septic rats, the colonization level of the challenge strain dropped at the beginning and then later increased during ceftriaxone treatment, after which it declined gradually. This pattern coincided with the change in resistance ofK. pneumoniaeto ceftriaxone during and after ceftriaxone treatment. Compared with burn-only injury, severe sepsis had a more significant effect on the change in antimicrobial resistance to ceftriaxone. Only in septic rats was the resistance gene successfully transferred from the challenge strain to endogenousE. coliduring ceftriaxone treatment; the gene persisted for at least 4 weeks after ceftriaxone treatment. We concluded that severe sepsis can facilitate intestinal colonization by an exogenous resistant pathogen and the transfer of the resistance gene to a potential endogenous pathogen during antimicrobial treatment.

scholarly journals Activity of NXL104 in Combination with β-Lactams against Genetically Characterized Escherichia coli and Klebsiella pneumoniae Isolates Producing Class A Extended-Spectrum β-Lactamases and Class C β-Lactamases

2011 ◽  
Vol 55 (5) ◽  
pp. 2434-2437 ◽  
Author(s):  
P. R. S. Lagacé-Wiens ◽  
F. Tailor ◽  
P. Simner ◽  
M. DeCorby ◽  
J. A. Karlowsky ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
The Novel ◽  
Content Type ◽  
E Coli ◽  
Class A ◽  
Extended Spectrum ◽  
Class C ◽  
Lactamase Inhibitor

ABSTRACTThe novel non-β-lactam β-lactamase inhibitor NXL104, in combination with cefepime, ceftazidime, ceftriaxone, amdinocillin, and meropenem, was tested against 190 extended-spectrum β-lactamase (ESBL)-producingEscherichia coliandKlebsiella pneumoniaeisolates, 94 AmpC-hyperproducingE. coliisolates, and 8 AmpC/ESBL-coexpressingE. coliisolates. NXL104 restored 100% susceptibility to the partner cephalosporins for all isolates tested. Amdinocillin and meropenem MICs were modestly improved (2 to 32 times lower) by NXL104. These results suggest that NXL104 may be useful in combination with β-lactams for the treatment of infections caused by ESBL- and AmpC-producingEnterobacteriaceae.

scholarly journals Hydrolysis Spectrum Extension of CMY-2-Like β-Lactamases Resulting from Structural Alteration in the Y-X-N Loop

2012 ◽  
Vol 56 (3) ◽  
pp. 1151-1156 ◽  
Author(s):  
Sandrine Dahyot ◽  
Hedi Mammeri
Keyword(s):  
Hot Spot ◽  
Catalytic Efficiency ◽  
Site Directed Mutagenesis ◽  
Hydrolysis Rate ◽  
Directed Mutagenesis ◽  
Content Type ◽  
E Coli ◽  
Class A ◽  
Extended Spectrum ◽  
Cloning Experiment

ABSTRACTTheCitrobacter freundiiisolate CHA, which was responsible for postoperative peritonitis after 10 days of cefepime therapy, displayed a phenotype of resistance consistent with extended-spectrum AmpC (ESAC) β-lactamase. The chromosome-borneblaAmpC-CHAgene was amplified and sequenced, revealing five amino acid substitutions, I125V, R148H, Q196H, V305A, and V348A, in the product compared to the sequence of native AmpC. A cloning experiment yielded theEscherichia coliTOP10(pAmpC-CHA) strain, which was resistant to all extended-spectrum cephalosporins (ESCs), including cefepime. To ascertain whether the R148H substitution accounted for the hydrolysis spectrum extension, it was reverted by site-directed mutagenesis. The resultingE. coliTOP10(pAmpC-CHA-H148R) strain was fully susceptible to cefepime, thus confirming that the Arg-148 replacement was mandatory for substrate profile enlargement. To further characterize the phenotypical and biochemical effects induced by the R148H change, it was introduced by site-directed mutagenesis into the CMY-2 β-lactamase, which is structurally related to the chromosome-borne cephalosporinase ofC. freundii. The CMY-2-R148H variant conferred increased MICs of ESCs, whereas those of carbapenems were unchanged even in a porin-deficientE. colistrain. Moreover, it exhibited increased catalytic efficiency (kcat/Km) toward ceftazidime (100-fold) due to an enhanced hydrolysis rate (kcat), whereas the enzymatic parameters toward imipenem were unchanged. The structural analysis of the AmpC variant showed that the R148H replacement occurred in the loop containing the Y-X-N motif, which is the counterpart of the SDN loop in class A β-lactamases. This study shows that the Y-X-N loop is a novel hot spot for mutations accounting for hydrolysis spectrum extension in CMY-2-type enzymes.

scholarly journals Acquisition of Extended-Spectrum β-Lactamases by Escherichia coli and Klebsiella pneumoniae in Gut Microbiota of Pilgrims during the Hajj Pilgrimage of 2013

2016 ◽  
Vol 60 (5) ◽  
pp. 3222-3226 ◽  
Author(s):  
Thongpan Leangapichart ◽  
Ndèye Méry Dia ◽  
Abiola Olumuyiwa Olaitan ◽  
Philippe Gautret ◽  
Philippe Brouqui ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Gut Microbiota ◽  
Detection Rate ◽  
M Gene ◽  
Content Type ◽  
E Coli ◽  
Extended Spectrum

ABSTRACTWe reported the acquisition of extended-spectrum-β-lactamase (ESBL)-producing bacteria in rectal samples of 129 pilgrims during the 2013 Hajj (pilgrimage to Makkah). When returning from the Hajj, there was a significant increase in the number of pilgrims carryingE. coliresistant to ceftriaxone (P= 0.008). The CTX-M gene was detected in rectal samples, with the detection rate increasing from 10.08% to 32.56% of samples after the Hajj (P< 0.001).

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