Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1855645 (KPC)
 1,473 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbapenem resistance due to KPC has rarely been observed outside the United States. We noticed a sharp increase in carbapenem-resistant Klebsiella pneumoniae strains possessing KPC in Tel Aviv Medical Center from 2004 to 2006. Sixty percent of the isolates belonged to a single clone susceptible only to gentamicin and colistin and carried the bla(KPC-3) gene, while almost all other clones carried the bla(KPC-2) gene. This rapid dissemination of KPC outside the United States is worrisome.
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PMID:Emergence of KPC-2 and KPC-3 in carbapenem-resistant Klebsiella pneumoniae strains in an Israeli hospital. 1756

Strains of Klebsiella pneumoniae that produce one of three possible carbapenemases--KPC--have recently been identified with increasing frequency among isolates recovered from patients residing along the East Coast of the United States, particularly within the New York City metropolitan region. These strains have exhibited resistance to multiple antibiotic classes, including carbapenem agents. We report a case of nosocomial pneumonia and empyema caused by a KPC-producing isolate of K. pneumoniae at a large midwestern U.S. tertiary care facility in which the patient was treated with tigecycline. Although the pneumonia was treated successfully, the empyema recurred in association with a treatment-emergent tigecycline minimum inhibitory concentration (MIC) increase from 0.75 to 2 microg/ml. Clinicians should be aware of the potential occurrence of this treatment-emergent MIC increase, especially in the setting of sustained tigecycline therapy. In addition, the emergence of carbapenem-resistant Enterobacteriaceae reinforces the importance of antibiotic stewardship and strict infection control practices.
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PMID:Tigecycline for treatment of pneumonia and empyema caused by carbapenemase-producing Klebsiella pneumoniae. 1759 11

Carbapenems, such as imipenem and meropenem, are most often used to treat infections caused by enterobacteria that produce extended-spectrum beta-lactamases, and the emergence of enzymes capable of inactivating carbapenems would therefore limit the options for treatment. Carbapenem resistance in Enterobacteriaceae is rare, but class A beta-lactamases with activity against the carbapenems are becoming more prevalent within this bacterial family. The class A carbapenemases can phylogenetically be segregated into six different groups of which four groups are formed by members of the GES, KPC, SME, IMI/NMC-A enzymes, while SHV-38 and SFC-1 each separately constitute a group. The genes encoding the class A carbapenemases are either plasmid-borne or located on the chromosome of the host. The bla(GES) genes reside as gene cassettes on mainly class I integrons, whereas the bla(KPC) genes and a single bla(IMI-2) gene are flanked by transposable elements on plasmids. Class A carbapenemases hydrolyse penicillins, classical cephalosporins, monobactam, and imipenem and meropenem, and the enzymes are divided into four phenotypically different groups, namely group 2br, 2be, 2e and 2f, according to the Bush-Jacoby-Medeiros classification system. Class A carbapenemases are inhibited by clavulanate and tazobactam like other class A beta-lactamases.
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PMID:Class A carbapenemases. 1759 89

Carbapenemases are beta-lactamases with versatile hydrolytic capacities. They have the ability to hydrolyze penicillins, cephalosporins, monobactams, and carbapenems. Bacteria producing these beta-lactamases may cause serious infections in which the carbapenemase activity renders many beta-lactams ineffective. Carbapenemases are members of the molecular class A, B, and D beta-lactamases. Class A and D enzymes have a serine-based hydrolytic mechanism, while class B enzymes are metallo-beta-lactamases that contain zinc in the active site. The class A carbapenemase group includes members of the SME, IMI, NMC, GES, and KPC families. Of these, the KPC carbapenemases are the most prevalent, found mostly on plasmids in Klebsiella pneumoniae. The class D carbapenemases consist of OXA-type beta-lactamases frequently detected in Acinetobacter baumannii. The metallo-beta-lactamases belong to the IMP, VIM, SPM, GIM, and SIM families and have been detected primarily in Pseudomonas aeruginosa; however, there are increasing numbers of reports worldwide of this group of beta-lactamases in the Enterobacteriaceae. This review updates the characteristics, epidemiology, and detection of the carbapenemases found in pathogenic bacteria.
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PMID:Carbapenemases: the versatile beta-lactamases. 1763 Mar 34

The ciliate Tetrahymena, a model organism, contains divergent mitochondrial (Mt) genome with unusual properties, where half of its 44 genes still remain without a definitive function. These genes could be categorized into two major groups of KPC (known protein coding) and Ymf (genes without an identified function). To gain insights into the mechanisms underlying gene divergence and molecular evolution of Tetrahymena (T.) Mt genomes, we sequenced three Mt genomes of T.paravorax, T.pigmentosa, and T.malaccensis. These genomes were aligned and the analyses were carried out using several programs that calculate distance, nucleotide substitution (dn/ds), and their rate ratios (omega) on individual codon sites and via a sliding window approach. Comparative genomic analysis indicated a conserved putative transcription control sequence, a GC box, in a region where presumably transcription and replication initiate. We also found distinct features in Mt genome of T.paravorax despite similar genome organization among these approximately 47 kb long linear genomes. Another significant finding was the presence of at least one or more highly variable regions in Ymf genes where majority of substitutions were concentrated. These regions were mutation hotspots where elevated distances and the dn/ds ratios were primarily due to an increase in the number of nonsynonymous substitutions, suggesting relaxed selective constraint. However, in a few Ymf genes, accelerated rates of nonsynonymous substitutions may be due to positive selection. Similarly, on protein level the majority of amino acid replacements occurred in these regions. Ymf genes comprise half of the genes in Tetrahymena Mt genomes, so understanding why they have not been assigned definitive functions is an important aspect of molecular evolution. Importantly, nucleotide substitution types and rates suggest possible reasons for not being able to find homologues for Ymf genes. Additionally, comparative genomic analysis of complete Mt genomes is essential in identifying biologically significant motifs such as control regions.
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PMID:Complete mitochondrial genome sequence of three Tetrahymena species reveals mutation hot spots and accelerated nonsynonymous substitutions in Ymf genes. 1765 77

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Surveillance Program was designed to monitor the antimicrobial potency and spectrum of meropenem, and selected broad-spectrum comparison agents against pathogens from hospitalized patients. In the 2006 (year 8 of the study) United States sample, a total of 2841 isolates (94.7% compliance) including 641 Escherichia coli, 619 Klebsiella spp., 606 Pseudomonas aeruginosa, 456 oxacillin-susceptible Staphylococcus aureus, 300 streptococci, 149 Enterococcus faecalis, and 70 Gram-positive anaerobic organisms were tested by reference broth microdilution or agar dilution susceptibility methods. The carbapenems, especially meropenem, consistently demonstrated the lowest resistance rates against Enterobacteriaceae strains, and the fluoroquinolones had the highest and increasing resistance rates. The presence of qnr-mediated fluoroquinolone resistance was investigated using polymerase chain reaction methods but was only observed at very low levels (2.1%) and was not clonally associated. Confirmed extended-spectrum beta-lactamase rates for E. coli and Klebsiella spp. were only 4.8% and 5.0%, respectively, with mobile AmpC (CMY-2 and FOX-5) enzymes shown in 13 additional Enterobacteriaceae isolates. Clonally related KPC-type serine carbapenemase production (57 strains, 9.5%) was observed at a rate 2-fold greater than the prior year among Klebsiella spp. isolates, primarily from 1 geographic region (Middle Atlantic States). These MYSTIC Program (2006) results demonstrate the continued need to monitor the carbapenem class potency and spectrum of activity against Enterobacteriaceae as well as P. aeruginosa because of the documented presence of serine carbapenemases and rare incidence of metallo-beta-lactamases that may further compromise their activity and that of other beta-lactam agents.
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PMID:Activity of meropenem as serine carbapenemases evolve in US Medical Centers: monitoring report from the MYSTIC Program (2006). 1766 57

The structure of the class A extended-spectrum beta-lactamase GES-1 from Klebsiella pneumoniae has been determined to 1.1 A resolution. GES-1 has the characteristic active-site disulfide bond of the carbapenemase family of beta-lactamases and has a structure that is very similar to those of other known carbapenemases, including NMC-A, SME-1 and KPC-2. Most residues implicated in the catalytic mechanism of this class of enzyme are present in the GES-1 active site, including Ser70, which forms a covalent bond with the carbonyl C atom of the beta-lactam ring of the substrate during the formation of an acyl-enzyme intermediate, Glu166, which is implicated as both the acylation and deacylation base, and Lys73, which is also implicated as the acylation base. A water molecule crucial to catalysis is observed in an identical location as in other class A beta-lactamases, interacting with the side chains of Ser70 and Glu166. One important residue, Asn170, also normally a ligand for the hydrolytic water, is missing from the GES-1 active site. This residue is a glycine in GES-1 and the enzyme is unable to hydrolyze imipenem. This points to this residue as being critically important in the hydrolysis of this class of beta-lactam substrate. This is further supported by flexible-docking studies of imipenem with in silico-generated Gly170Asn and Gly170Ser mutant GES-1 enzymes designed to mimic the active sites of imipenem-hydrolyzing point mutants GES-2 and GES-5.
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PMID:Structure of GES-1 at atomic resolution: insights into the evolution of carbapenamase activity in the class A extended-spectrum beta-lactamases. 1770 67

Carbapenemases are beta-lactamases that hydrolyze most beta-lactams including carbapenems. Carbapenemases are classified in four molecular classes; those belonging to class A are the chromosomally-encoded and clavulanic acid-inhibited IMI, NMC-A and SME, identified in Enterobacter cloacae and Serratia marcescens; the plasmid-encoded KPC enzymes identified in Enterobacteriaceae (and rarely in Pseudomonas aeruginosa); and the GES-type enzymes identified in Enterobacteriaceae and P. aeruginosa. The class B enzymes are the most clinically-significant carbapenemases; they are metallo-beta-lactamases, mostly of the IMP and the VIM series. They have been reported worldwide and their genes are plasmid- and integron-located, hydrolyzing all beta-lactams with the exception of aztreonam. One single plasmid-mediated AmpC beta-lactamase, CMY-10, identified in an Enterobacter aerogenes isolate, has been shown to be a cephaslosporinase with some carbapenemase properties. Finally, the class D carbapenemases are being increasingly reported, mostly in Acinetobacter baumannii, and they compromise the efficacy of imipenem and meropenem significantly.
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PMID:Carbapenemases: molecular diversity and clinical consequences. 1792 73

This report describes an outbreak of carbapenem-resistant KPC-3-producing Klebsiella pneumoniae outside the USA. Ninety patients from different departments of a tertiary medical centre were diagnosed with carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-negative Klebsiella pneumoniae infection by standard methods over a 10-month period in 2006. Fifteen randomly selected outbreak isolates were subjected to randomly amplified polymorphic DNA (RAPD) polymerase chain reaction (PCR) as well as PCR amplification and sequencing of the KPC genes, and the findings were compared with two carbapenem-susceptible K. pneumoniae isolates (one ESBL-positive and one ESBL-negative). All the outbreak isolates were resistant to all fluoroquinolones and beta-lactam antibiotics tested, including carbapenems, and were sensitive only to colistin, gentamicin and most of them also to tigecycline. On RAPD-PCR, all 15 outbreak isolates were identical to each other and clearly distinguishable from control strains, indicating clonality. The KPC-3 enzyme was identified by nucleotide sequencing analysis in all outbreak isolates but not in the control strains. These findings should alert government and medical authorities to institute stringent control measures and to initiate research into therapeutic and preventive strategies.
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PMID:Outbreak of carbapenem-resistant Klebsiella pneumoniae producing KPC-3 in a tertiary medical centre in Israel. 1793 35

A total of 104 carbapenemase (serine- and metallo-beta-lactamase [MbetaL])-producing strains of the Enterobacteriaceae family collected from 2000 to 2005 in medical centers distributed worldwide were tested against tigecycline and 25 comparators by reference broth microdilution methods. The most frequent carbapenemase was KPC-2 or -3 (73 strains), followed by VIM-1 (14), IMP-1 (11), SME-2 (5), and NMC-A (1). All serine carbapenemases were detected in the United States, while MbetaL-producing strains were isolated in Europe. Carbapenemase-producing Enterobacteriaceae showed high rates of resistance to most antimicrobial agents tested. The rank order of in vitro activity against these strains was as follows: tigecycline (100.0% susceptible) > polymyxin B (88.1%) > amikacin (73.0%) > imipenem (37.5%). Tigecycline was very active (MIC(90), 1 microg/ml) against this significant, contemporary collection of well-characterized strains and appears to be an excellent option compared to the polymyxins for treatment of infections caused by these multidrug-resistant Enterobacteriaceae.
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PMID:Antimicrobial activities of tigecycline and other broad-spectrum antimicrobials tested against serine carbapenemase- and metallo-beta-lactamase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program. 1807 Sep 60


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