scholarly journals Carbapenem Resistance Caused by High-Level Expression of OXA-663 β-Lactamase in an OmpK36-Deficient Klebsiella pneumoniae Clinical Isolate

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Peijun Ma ◽  
Hannah H. Laibinis ◽  
Christoph M. Ernst ◽  
Deborah T. Hung
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Isolate ◽  
Carbapenem Resistance ◽  
Combinatorial Complexity ◽  
High Level Expression ◽  
Content Type ◽  
Expression Levels ◽  
Extended Spectrum ◽  
High Level ◽  
Lactamase Gene

ABSTRACT Carbapenem resistance is mainly mediated by carbapenemases or extended-spectrum β-lactamases (ESBL) plus a loss of porins. However, we have identified a Klebsiella pneumoniae clinical isolate that contains neither carbapenemases nor ESBLs. Instead, we found that high-level expression of a novel blaOXA-10-derived β-lactamase gene, blaOXA-663, in conjunction with OmpK36 deficiency results in high-level carbapenem resistance. This finding demonstrates the combinatorial complexity of factors, including β-lactamase activity, its expression levels, and porin activity, that yield carbapenem resistance.

scholarly journals Effects of Klebsiella pneumoniae Carbapenemase Subtypes, Extended-Spectrum β-Lactamases, and Porin Mutations on theIn VitroActivity of Ceftazidime-Avibactam against Carbapenem-Resistant K. pneumoniae

2015 ◽  
Vol 59 (9) ◽  
pp. 5793-5797 ◽  
Author(s):  
Ryan K. Shields ◽  
Cornelius J. Clancy ◽  
Binghua Hao ◽  
Liang Chen ◽  
Ellen G. Press ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Mechanisms Of Resistance ◽  
Content Type ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
High Level ◽  
Emergence Of Resistance

ABSTRACTAvibactam is a novel β-lactamase inhibitor with affinity forKlebsiella pneumoniaecarbapenemases (KPCs). In combination with ceftazidime, the agent demonstrates activity against KPC-producingK. pneumoniae(KPC-Kp). KPC-Kp strains are genetically diverse and harbor multiple resistance determinants, including defects in outer membrane proteins and extended-spectrum β-lactamases (ESBLs). Mutations in porin geneompK36confer high-level carbapenem resistance to KPC-Kp strains. Whether specific mechanisms of antimicrobial resistance also influence the activity of ceftazidime-avibactam is unknown. We defined the effects of ceftazidime-avibactam against 72 KPC-Kp strains with diverse mechanisms of resistance, including various combinations of KPC subtypes and ESBL andompK36mutations. Ceftazidime MICs ranged from 64 to 4,096 μg/ml and were lowered by a median of 512-fold with the addition of avibactam. All strains exhibited ceftazidime-avibactam MICs at or below the CLSI breakpoint for ceftazidime (≤4 μg/ml; range, 0.25 to 4). However, the MICs were within two 2-fold dilutions of the CLSI breakpoint against 24% of the strains, and those strains would be classified as nonsusceptible to ceftazidime by EUCAST criteria (MIC > 1 μg/ml). Median ceftazidime-avibactam MICs were higher against KPC-3 than KPC-2 variants (P= 0.02). Among KPC-2-Kp strains, the presence of both ESBL and porin mutations was associated with higher drug MICs compared to those seen with either factor alone (P= 0.003 andP= 0.02, respectively). In conclusion, ceftazidime-avibactam displays activity against genetically diverse KPC-Kp strains. Strains with higher-level drug MICs provide a reason for caution. Judicious use of ceftazidime-avibactam alone or in combination with other agents will be important to prevent the emergence of resistance.

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 Biochemical Characterization of the TEM-107 Extended-Spectrum β-Lactamase in a Klebsiella pneumoniae Isolate from South Korea

2011 ◽  
Vol 55 (12) ◽  
pp. 5930-5932 ◽  
Author(s):  
Kyungwon Lee ◽  
Jong Hwa Yum ◽  
Dongeun Yong ◽  
Seok Hoon Jeong ◽  
Gian Maria Rossolini ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
South Korea ◽  
Clavulanic Acid ◽  
Clinical Isolate ◽  
Biochemical Characterization ◽  
Content Type ◽  
Extended Spectrum

ABSTRACTThe TEM-107 extended-spectrum β-lactamase detected in aKlebsiella pneumoniaeclinical isolate had a Gly238Ser substitution compared to the TEM-43 β-lactamase. The MIC of ceftazidime was higher (64 μg/ml) than that of cefotaxime (2 μg/ml) for the isolate. Clavulanic acid reduced the MIC of ceftazidime 64-fold.

scholarly journals Rapid Induction of High-Level Carbapenem Resistance in Heteroresistant KPC-Producing Klebsiella pneumoniae

2015 ◽  
Vol 59 (6) ◽  
pp. 3281-3289 ◽  
Author(s):  
Sheila Adams-Sapper ◽  
Shantell Nolen ◽  
Grace Fox Donzelli ◽  
Mallika Lal ◽  
Kunihiko Chen ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Laboratory ◽  
Carbapenem Resistance ◽  
Content Type ◽  
Rapid Induction ◽  
Drug Concentrations ◽  
Imipenem Resistance ◽  
High Level ◽  
Testing Standards ◽  
Time Kill

ABSTRACTEnterobacteriaceaestrains producing theKlebsiella pneumoniaecarbapenemase (KPC) have disseminated worldwide, causing an urgent threat to public health. KPC-producing strains often exhibit low-level carbapenem resistance, which may be missed by automated clinical detection systems. In this study, eightKlebsiella pneumoniaestrains with heterogeneous resistance to imipenem were used to elucidate the factors leading from imipenem susceptibility to high-level resistance as defined by clinical laboratory testing standards. Time-kill analysis with an inoculum as low as 3 × 106CFU/ml and concentrations of imipenem 8- and 16-fold higher than the MIC resulted in the initial killing of 99.9% of the population. However, full recovery of the population occurred by 20 h of incubation in the same drug concentrations. Population profiles showed that recovery was mediated by a heteroresistant subpopulation at a frequency of 2 × 10−7to 3 × 10−6. Samples selected 2 h after exposure to imipenem were as susceptible as the unexposed parental strain and produced the major outer membrane porin OmpK36. However, between 4 to 8 h after exposure, OmpK36 became absent, and the imipenem MIC increased at least 32-fold. Individual colonies isolated from cultures after 20 h of exposure revealed both susceptible and resistant subpopulations. Once induced, however, the high-level imipenem resistance was maintained, and OmpK36 remained unexpressed even without continued carbapenem exposure. This study demonstrates the essential coordination betweenblaKPCandompK36expression mediating high-level imipenem resistance from a population of bacteria that initially exhibits a carbapenem-susceptibility phenotype.

scholarly journals Characteristics of Extended-Spectrum β-Lactamase- and Carbapenemase-Producing Enterobacteriaceae Isolates from Rivers and Lakes in Switzerland

2013 ◽  
Vol 79 (9) ◽  
pp. 3021-3026 ◽  
Author(s):  
Katrin Zurfluh ◽  
Herbert Hächler ◽  
Magdalena Nüesch-Inderbinen ◽  
Roger Stephan
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Content Type ◽  
Extended Spectrum ◽  
Rivers And Lakes ◽  
Genes Encoding ◽  
River Sample ◽  
Severe Infections ◽  
Enterobacter Amnigenus

ABSTRACTOne of the currently most relevant resistance mechanisms inEnterobacteriaceaeis the production of enzymes that lead to modern expanded-spectrum cephalosporin and even carbapenem resistance, mainly extended-spectrum β-lactamases (ESBLs) and carbapenemases. A worrisome aspect is the spread of ESBL and carbapenemase producers into the environment. The aim of the present study was to assess the occurrence of ESBL- and carbapenemase-producingEnterobacteriaceaeand to further characterize ESBL- and carbapenemase-producingEnterobacteriaceaein rivers and lakes in Switzerland. ESBL-producingEnterobacteriaceaewere detected in 21 (36.2%) of the 58 bodies of water sampled. One river sample tested positive for a carbapenemase-producingKlebsiella pneumoniaesubsp.pneumoniaestrain. Seventy-four individual strains expressing an ESBL phenotype were isolated. Species identification revealed 60Escherichia colistrains, sevenKlebsiella pneumoniaesubsp.pneumoniaestrains, fiveRaoultella planticolastrains, oneEnterobacter cloacaestrain, and oneEnterobacter amnigenusstrain. Three strains were identified as SHV-12 ESBL producers, and 71 strains carried genes encoding CTX-M ESBLs. Of the 71 strains with CTX-M ESBL genes, 8 isolates expressed CTX-M-1, three produced CTX-M-3, 46 produced CTX-M-15, three produced CTX-M-55, one produced CTX-M-79, six produced CTX-M-14, and four produced CTX-M-27. Three of the four CTX-M-27 producers belonged to the multiresistant pandemic sequence typeE. coliB2:ST131 that is strongly associated with potentially severe infections in humans and animals.

scholarly journals Coproduction of 16S rRNA Methyltransferase RmtD or RmtG with KPC-2 and CTX-M Group Extended-Spectrum β-Lactamases in Klebsiella pneumoniae

2013 ◽  
Vol 57 (5) ◽  
pp. 2397-2400 ◽  
Author(s):  
Maria Fernanda C. Bueno ◽  
Gabriela R. Francisco ◽  
Jessica A. O'Hara ◽  
Doroti de Oliveira Garcia ◽  
Yohei Doi
Keyword(s):  
Amino Acid ◽  
16S Rrna ◽  
Klebsiella Pneumoniae ◽  
Amino Acid Identity ◽  
Aminoglycoside Resistance ◽  
Content Type ◽  
Acid Identity ◽  
Paulo State ◽  
Extended Spectrum ◽  
High Level

ABSTRACTEightKlebsiella pneumoniaeclinical strains with high-level aminoglycoside resistance were collected from eight hospitals in São Paulo State, Brazil, in 2010 and 2011. Three of them produced an RmtD group 16S rRNA methyltransferase, RmtD1 or RmtD2. Five strains were found to produce a novel 16S rRNA methyltransferase, designated RmtG, which shared 57 to 58% amino acid identity with RmtD1 and RmtD2. Seven strains coproduced KPC-2 with or without various CTX-M group extended-spectrum β-lactamases, while the remaining strain coproduced CTX-M-2.

scholarly journals In Vivo Evolution of CTX-M-215, a Novel Narrow-Spectrum β-Lactamase in an Escherichia coli Clinical Isolate Conferring Resistance to Mecillinam

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mengyun Yin ◽  
Guoping Hu ◽  
Zhen Shen ◽  
Chengli Fang ◽  
Xuefei Zhang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Clinical Isolate ◽  
High Similarity ◽  
Content Type ◽  
Narrow Spectrum ◽  
Extended Spectrum ◽  
Hydrolytic Activities ◽  
High Level ◽  
Level Resistance

ABSTRACT Here, we report a novel narrow-spectrum β-lactamase CTX-M-215 identified in an Escherichia coli clinical isolate in China and conferring high-level resistance to mecillinam but not to cefotaxime. CTX-M-215 differed from CTX-M-125, a CTX-M extended-spectrum β-lactamase (ESBL), by an N132D substitution, which decreased hydrolytic activities toward penicillins and cephalosporins except for mecillinam. High similarity was observed between CTX-M-215- and CTX-M-125-bearing plasmids, carried by different isolates in the same patient, indicating in vivo evolution of CTX-M-215 from CTX-M-125.

scholarly journals Novel Carbapenem-Hydrolyzing β-Lactamase, KPC-1, from a Carbapenem-Resistant Strain of Klebsiella pneumoniae

2001 ◽  
Vol 45 (4) ◽  
pp. 1151-1161 ◽  
Author(s):  
Hesna Yigit ◽  
Anne Marie Queenan ◽  
Gregory J. Anderson ◽  
Antonio Domenech-Sanchez ◽  
James W. Biddle ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clavulanic Acid ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Kinetic Studies ◽  
The Novel ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
High Level

ABSTRACT A Klebsiella pneumoniae isolate showing moderate to high-level imipenem and meropenem resistance was investigated. The MICs of both drugs were 16 μg/ml. The β-lactamase activity against imipenem and meropenem was inhibited in the presence of clavulanic acid. The strain was also resistant to extended-spectrum cephalosporins and aztreonam. Isoelectric focusing studies demonstrated three β-lactamases, with pIs of 7.2 (SHV-29), 6.7 (KPC-1), and 5.4 (TEM-1). The presence of bla SHV andbla TEM genes was confirmed by specific PCRs and DNA sequence analysis. Transformation and conjugation studies withEscherichia coli showed that the β-lactamase with a pI of 6.7, KPC-1 (K. pneumoniae carbapenemase-1), was encoded on an approximately 50-kb nonconjugative plasmid. The gene,bla KPC-1, was cloned in E. coli and shown to confer resistance to imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The amino acid sequence of the novel carbapenem-hydrolyzing β-lactamase, KPC-1, showed 45% identity to the pI 9.7 carbapenem-hydrolyzing β-lactamase, Sme-1, fromSerratia marcescens S6. Hydrolysis studies showed that purified KPC-1 hydrolyzed not only carbapenems but also penicillins, cephalosporins, and monobactams. KPC-1 had the highest affinity for meropenem. The kinetic studies also revealed that clavulanic acid and tazobactam inhibited KPC-1. An examination of the outer membrane proteins of the parent K. pneumoniae strain demonstrated that the strain does not express detectable levels of OmpK35 and OmpK37, although OmpK36 is present. We concluded that carbapenem resistance in K. pneumoniae strain 1534 is mainly due to production of a novel Bush group 2f, class A, carbapenem-hydrolyzing β-lactamase, KPC-1, although alterations in porin expression may also play a role.

scholarly journals KPC-53, a KPC-3 Variant of Clinical Origin Associated with Reduced Susceptibility to Ceftazidime-Avibactam

2020 ◽  
Vol 65 (1) ◽  
pp. e01429-20
Author(s):  
Vincenzo Di Pilato ◽  
Noemi Aiezza ◽  
Valentina Viaggi ◽  
Alberto Antonelli ◽  
Luigi Principe ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Clinical Isolate ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Mechanisms Of Resistance ◽  
Content Type ◽  
High Level ◽  
Level Resistance

ABSTRACTThis study reports on the characterization of a Klebsiella pneumoniae clinical isolate showing high-level resistance to ceftazidime-avibactam associated with the production of KPC-53, a KPC-3 variant exhibiting a Leu167Glu168 duplication in the Ω-loop and a loss of carbapenemase activity. Whole-genome sequencing (WGS) revealed the presence of two copies of blaKPC-53, located on a pKpQIL-like plasmid and on a plasmid prophage of the Siphoviridae family, respectively. The present findings provide new insights into the mechanisms of resistance to ceftazidime-avibactam.

scholarly journals Novel Conjugative Plasmid from Escherichia coli of Swine Origin That Coharbors the Multiresistance Genecfrand the Extended-Spectrum-β-Lactamase GeneblaCTX-M-14b

2014 ◽  
Vol 59 (2) ◽  
pp. 1337-1340 ◽  
Author(s):  
Wan-Jiang Zhang ◽  
Xiu-Mei Wang ◽  
Lei Dai ◽  
Xin Hua ◽  
Zhimin Dong ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Conjugative Plasmid ◽  
Content Type ◽  
Conjugative Plasmids ◽  
Extended Spectrum ◽  
Lactamase Gene

ABSTRACTTwo porcineEscherichia coliisolates harbored thecfrgene on conjugative plasmids of 38,405 bp (pGXEC6) and 41,646 bp (pGXEC3). In these two plasmids, thecfrgene was located within a 4,612-bp region containing atnpA-IS26-cfr-IS26-Δhypelement. Plasmid pGXEC3 was almost identical to pGXEC6 except for a 3,235-bp ISEcp1-blaCTX-M-14binsertion. The colocation of the multiresistancecfrgene with an extended-spectrum-β-lactamase gene on a conjugative plasmid may support the dissemination of these genes by coselection.

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