Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0519030 (Klebsiella)
 21,988 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

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 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

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

Klebsiella pneumoniae isolates harboring KPC enzymes have been identified in many geographical areas since 2001. Numerous problems exist in the detection and treatment of patients with such isolates. The clinical characteristics and molecular epidemiology associated with 12 randomly chosen patients in whom these enzymes were detected by molecular methods are described. This is the first description of the identification of carbapenem-resistant K. pneumoniae isolates harboring KPC beta-lactamases at the Veterans Administration Hospital in New Jersey (VA NJHCS). Because recognition of carbapenem resistance in K. pneumoniae due to KPC enzymes can only be achieved by molecular methods, detection in the Clinical Microbiology Laboratory by routine methods will continue to be difficult, leading to dilemmas in treatment.
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PMID:Identification of carbapenem-resistant klebsiella pneumoniae harboring KPC enzymes in New Jersey. 1818 49

Although much of today's media focuses on multidrug-resistant gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, resistance within gram-negative bacilli continues to rise, occasionally creating situations in which few or no antibiotics that retain activity are available. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella sp are emerging threats nationally. Although carbapenems are considered the antibiotic class of choice to treat ESBL-producing Enterobacteriaceae, the ability of these organisms to produce carbapenemases has now become apparent in some regions throughout the United States. Although still rare, Klebsiella sp that produce KPC-2 retain susceptibility only to tigecycline, polymyxins, and occasionally aminoglycosides. Multidrug resistance among Pseudomonas aeruginosa and Acinetobacter sp has always been apparent across many hospitals in the United States. Recent surveillance indicates increasing resistance to all currently available antibiotics, including carbapenems, cephalosporins, penicillins, fluoroquinolones, and aminoglycosides. Against many strains, only polymyxins retain activity; however, resistance has also been reported to these agents. Fortunately, resistance mechanisms such as metallo-beta-lactamases are still rare in the United States. As no new antibiotics with novel mechanisms against many of these gram-negative bacilli are expected to be developed in the foreseeable future, careful and conservative use of agents combined with good infection control practices is required.
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PMID:The current state of multidrug-resistant gram-negative bacilli in North America. 1822 69

Genetic structures surrounding the carbapenem-hydrolyzing Ambler class A bla KPC gene were characterized in several KPC-positive Klebsiella pneumoniae and Pseudomonas aeruginosa strains isolated from the United States, Colombia, and Greece. The bla KPC genes were associated in all cases with transposon-related structures. In the K. pneumoniae YC isolate from the United States, the beta-lactamase bla KPC-2 gene was located on a novel Tn3-based transposon, Tn4401. Tn4401 was 10 kb in size, was delimited by two 39-bp imperfect inverted repeat sequences, and harbored, in addition to the beta-lactamase bla KPC-2 gene, a transposase gene, a resolvase gene, and two novel insertion sequences, ISKpn6 and ISKpn7. Tn4401 has been identified in all isolates. However, two isoforms of this transposon were found: Tn4401a was found in K. pneumoniae YC and K. pneumoniae GR from the United States and Greece, respectively, and differed by a 100-bp deletion, located just upstream of the bla KPC-2 gene, compared to the sequence of Tn4401b, which was found in the Colombian isolates. In all isolates tested, Tn4401 was flanked by a 5-bp target site duplication, the signature of a recent transposition event, and was inserted in different open reading frames located on plasmids that varied in size and nature. Tn4401 is likely at the origin of carbapenem-hydrolyzing beta-lactamase KPC mobilization to plasmids and its further insertion into various-sized plasmids identified in nonclonally related K. pneumoniae and P. aeruginosa isolates.
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PMID:Genetic structures at the origin of acquisition of the beta-lactamase bla KPC gene. 1822 85

Since 1997, the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program has monitored the antimicrobial activity of broad-spectrum agents against pathogens from hospitalized patients. In the United States, 2894 isolates were submitted in 2007 from 15 sites, including 1392 Enterobacteriaceae, 643 nonfermentative Gram-negative bacilli, and 829 Gram-positive cocci. All isolates were tested by broth microdilution methods. Meropenem (MIC(90) range, 0.12-2 microg/mL) exhibited the lowest resistance rates (1.9-2.4%) against Enterobacteriaceae, and fluoroquinolones had the highest rates of resistance (17.3-18.3%). KPC carbapenemases, usually found in Klebsiella pneumoniae, were also detected in Citrobacter freundii, Enterobacter spp., and Escherichia coli. Confirmed extended-spectrum beta-lactamase-producing isolate rates for E. coli, Klebsiella spp., and Proteus mirabilis isolates were 6.0%, 12.0%, and 0.0%, respectively. Meropenem remained active against Gram-positive pathogens such as staphylococci (methicillin-susceptible; MIC(90), 0.12-0.25 microg/mL), Streptococcus pneumoniae (MIC(90), 0.5 microg/mL), and beta-hemolytic and viridans group streptococci (MIC(90) range, 0.06-0.25 microg/mL). These US MYSTIC Program results demonstrate the continued emergence of novel beta-lactamases and multidrug-resistant bacterial phenotypes necessitating monitoring of carbapenem activities against Enterobacteriaceae species as well as nonfermentative bacilli.
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PMID:Comparative activity of meropenem in US medical centers (2007): initiating the 2nd decade of MYSTIC program surveillance. 1832 35


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