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)

Among 257 isolates of Klebsiella pneumoniae collected in Brooklyn, NY, 24% were found to possess bla(KPC). Clinical microbiology laboratories that used automated broth microdilution systems reported 15% of the KPC-possessing isolates as susceptible to imipenem. The imipenem MIC was found to be markedly affected by the inoculum. For accurate detection of KPC-possessing K. pneumoniae, particular attention should be paid to proper inoculum preparation for broth-based susceptibility methods. In addition, using ertapenem or meropenem for class reporting of carbapenem susceptibility will improve detection.
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PMID:Emergence of KPC-possessing Klebsiella pneumoniae in Brooklyn, New York: epidemiology and recommendations for detection. 1598 Mar 89

Among 8885 Enterobacteriaceae tested in the 1999 to 2005 period as part of the USA Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program, 51 strains with increased imipenem and meropenem MIC values (> or =2 microg/mL) were detected. bla(KPC) was identified from 28 Klebsiella pneumoniae from 3 medical centers in the New York City area (8 ribotypes), 2 Klebsiella oxytoca from Arkansas (same ribotype), 7 Citrobacter freundii (6 from New York [5 ribotypes] and 1 from Delaware), 4 Enterobacter spp. from New York (2 species, different ribotypes), 3 Escherichia coli (2 from New York and 1 from Ohio, same ribotype), and 1 Serratia marcescens (New York). Sequencing confirmed KPC-2 or -3 in all of the strains. S. marcescens strains harboring SME-1 (2 isolates, same ribotype) and SME-2 (1 isolate) were identified from medical centers in Illinois and Washington state, respectively. Our results indicate that bla(KPC-2/3) has emerged widely (New York City area, Arkansas, Delaware, and Ohio) among Enterobacteriaceae isolated in the MYSTIC Program participant sites (2000-2005) and continues to be isolated from multiple species, as a result of clonal expansion and horizontal gene transfer. The escalating occurrence (0.35%) of serine carbapenemases could compromise the role of carbapenems and other beta-lactams in USA clinical practice although observed in only a few locations to date.
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PMID:Emergence of serine carbapenemases (KPC and SME) among clinical strains of Enterobacteriaceae isolated in the United States Medical Centers: report from the MYSTIC Program (1999-2005). 1702 Jul 98

Emergence and dissemination of Enterobacteriaceae isolates harboring carbapenemases in various geographic regions represents a significant threat to the management of nosocomial infections. Enterobacteriaceae isolates from the SENTRY Antimicrobial Surveillance Program (2000-2004) demonstrating decreased susceptibility to imipenem and meropenem (minimum inhibitory concentration [MIC], > or =2 mg/L) were evaluated for the production of metallo-beta-lactamases and serine carbapenemases using disk approximation and polymerase chain reaction (PCR) tests. Carbapenemase-producing strains were epidemiologically typed by automated riboprinting and pulsed-field gel electrophoresis (PFGE) to establish clonality. Among 37,557 Enterobacteriaceae (5 genus groups) evaluated, 119 (0.32%) had increased carbapenem MIC values, and a carbapenemase was identified in 51 (42.9%) of these strains. KPC-2 and KPC-3 were the most frequently occurring carbapenemases (24 isolates, 20.2%) in the United States and were detected in Klebsiella spp, Citrobacter spp., Enterobacter spp., and Serratia marcescens strains isolated in New York, Arkansas, and Virginia. SME-2-producing S. marcescens were isolated in the New York City area, Texas, and Ohio, while NMC-A was found in one E. cloacae strain from New York. In contrast, metallo-beta-lactamases were prevalent in Europe. IMP-1-producing E. cloacae (11 isolates) were detected in Turkey, while VIM-1-producing strains were found in Italy (Enterobacter spp.) and Greece (Klebsiella pneumoniae). Clonal dissemination of carbapenemase-producing strains was observed in several medical centers on both continents. The occurrence of carbapenemases in various Enterobacteriaceae remains rare but appears to be spreading geographically (not in Latin America), mainly with metallo-beta-lactamases being found in Mediterranean Europe and KPC enzymes in the New York City area.
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PMID:Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000-2004). 1722 6

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

An imipenem-resistant isolate of Citrobacter freundii ZJ163 (MIC 256 microg ml(-1)) isolated from a Chinese hospital was investigated. The C. freundii ZJ163 isolate exhibited high-level resistance to carbapenems, penicillins, cephalosporins, cefoxitin, aztreonam, quinolones and aminoglycosides. Isoelectric focusing (IEF) demonstrated three beta-lactamases with pIs of 5.4 (TEM-1), 6.7 (KPC-2) and 7.9 (CTX-M-14). Two different transconjugants (types A and B) were obtained by conjugation studies. The type A transconjugant exhibited reduced susceptibility or resistance to penicillins, cephalosporins and aztreonam, but was susceptible to carbapenems, quinolones and aminoglycosides. The antimicrobial susceptibility patterns of the type B transconjugant were similar to that of type A, except for its significantly reduced carbapenem susceptibility (imipenem MIC 2 microg ml(-1)). IEF, specific PCRs and DNA sequence analysis indicated that the type A transconjugant produced CTX-M-14 beta-lactamase with a pI of 7.9, that the type B transconjugant produced KPC-2 beta-lactamase with a pI of 6.7 and that the beta-lactamase with a pI of 5.4 was TEM-1. PCR analysis and sequencing confirmed the presence of the ampC gene in the chromosomal DNA from C. freundii ZJ163, although no activity of AmpC beta-lactamase was detected by IEF. Urea/SDS-PAGE analysis of outer-membrane proteins revealed that the levels of the 41 and 38 kDa porins were decreased in C. freundii ZJ163. It was concluded that production of KPC-2 combined with decreased expression of porins contributes to high-level resistance to carbapenems in C. freundii ZJ163.
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PMID:High-level carbapenem resistance in a Citrobacter freundii clinical isolate is due to a combination of KPC-2 production and decreased porin expression. 1828 96

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

In concert with the development of novel beta-lactams and broad-spectrum cephalosporins, bacterially encoded beta-lactamases have evolved to accommodate the new agents. This study was designed to identify, at the sequence level, the genes responsible for the extended-spectrum-beta-lactamase (ESBL) phenotypes of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolates collected during the global tigecycline phase 3 clinical trials. PCR assays were developed to identify and clone the bla(TEM), bla(SHV), bla(OXA), and bla(CTX) genes from clinical strains. Isolates were also screened for AmpC genes of the bla(CMY), bla(ACT), bla(FOX), and bla(DHA) families as well as the bla(KPC) genes encoding class A carbapenemases. E. coli, K. pneumoniae, and P. mirabilis isolates with ceftazidime MICs of > or =2 microg/ml were designated possible ESBL-producing pathogens and were then subjected to a confirmatory test for ESBLs by use of Etest. Of 272 unique patient isolates, 239 were confirmed by PCR and sequencing to carry the genes for at least one ESBL, with 44% of the positive isolates harboring the genes for multiple ESBLs. In agreement with current trends for ESBL distribution, bla(CTX-M)-type beta-lactamase genes were found in 83% and 71% of the ESBL-positive E. coli and K. pneumoniae isolates, respectively, whereas bla(SHV) genes were found in 41% and 28% of the ESBL-positive K. pneumoniae and E. coli isolates, respectively. Ninety-seven percent of the E. coli and K. pneumoniae isolates were tigecycline susceptible (MIC(90) = 2 microg/ml), warranting further studies to define the therapeutic utility of tigecycline against strains producing ESBLs in a clinical setting.
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PMID:Characterization and sequence analysis of extended-spectrum-{beta}-lactamase-encoding genes from Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolates collected during tigecycline phase 3 clinical trials. 1901 60

The detection of class A serine-carbapenemases among species of Enterobacteriaceae remains a challenging issue. Methods of identification for routine use in clinical microbiology laboratories have not been standardized to date. We developed a novel screening methodology suitable for countries with high basal levels of carbapenem resistance due to non-carbapenemase-mediated mechanisms and standardized several simple confirmatory methods that allow the recognition of bacteria producing class A carbapenemases, including KPC, Sme, IMI, NMC-A, and GES, by using boronic acid (BA) derivatives. A total of 28 genetically unrelated Enterobacteriaceae strains producing several class A carbapenemases were tested. Thirty-eight genetically unrelated negative controls were included. The isolates were tested against imipenem (IPM), meropenem (MEM), and ertapenem (ETP) by MIC and disk diffusion assays in order to select appropriate tools to screen for suspected carbapenemase production. It was possible to differentiate class A carbapenemase-producing bacteria from non-carbapenemase-producing bacteria by using solely the routine IPM susceptibility tests. The modified Hodge test was evaluated and found to be highly sensitive, although false-positive results were documented. Novel BA-based methods (a double-disk synergy test and combined-disk and MIC tests) using IPM, MEM, and ETP, in combination with 3-aminophenylboronic acid as an inhibitor, were designed as confirmatory tools. On the basis of the performance of these methods, a sensitive flow chart for suspicion and confirmation of class A carbapenemase production in species of Enterobacteriaceae was designed. By using this methodology, isolates producing KPC, GES, Sme, IMI, and NMC-A carbapenemases were successfully distinguished from those producing other classes of beta-lactamases (extended-spectrum beta-lactamases, AmpCs, and metallo-beta-lactamases, etc). These methods will rapidly provide useful information needed for targeting antimicrobial therapy and appropriate infection control.
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PMID:Sensitive screening tests for suspected class A carbapenemase production in species of Enterobacteriaceae. 1938 50

There are currently no standardized diagnostic tests available for the reliable detection of AmpC beta-lactamases in Klebsiella spp., Escherichia coli, Proteus mirabilis and Salmonella spp. A study was designed to evaluate a confirmation disk test using cefotetan (CTT) and cefoxitin (FOX) with phenylboronic acid (PBA). It also investigated the most suitable screening concentrations of FOX, ceftriaxone (CRO) and ceftazidime (CAZ) for the detection of AmpC beta-lactamases. A total of 126 control (consisting of 11 laboratory and 115 well-characterized clinical strains) and 29,840 non-repeat clinical isolates were included. FOX with PBA used in a confirmation test and CRO and CAZ as screening agents were found to be unreliable. FOX at >or= 32 mg/L was the best screening agent and CTT with PBA was the best confirmation test. Of the clinical isolates 635 (2%) were found to be resistant to cefoxitin (MIC >or= 32 ug/mL) and 332 (52%) were AmpC positive. E. coli was the most common organism with AmpC beta-lactamases and was mostly present in urines from community patients. It is recommended that laboratories use FOX at 32 mg/L as a screening agent and perform a disk test with CTT and PBA to confirm the presence of an AmpC cephalosporinase in isolates of Klebsiella spp., E. coli, Salmonella spp. and P. mirabilis. This approach is convenient, practical and easy to incorporate into the workflow of a clinical laboratory. False-positive AmpC detection may occur with KPC-producing bacteria when inhibitor-based methods are used.
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PMID:Detection of AmpC beta-lactamases in Escherichia coli, Klebsiella spp., Salmonella spp. and Proteus mirabilis in a regional clinical microbiology laboratory. 1945 38

To verify the presence of Klebsiella pneumoniae carbapenemase-producing (KPC-producing) Klebsiella pneumoniae in Greece, we asked 40 Greek hospitals participating in the Greek System for the Surveillance of Antimicrobial Resistance (GSSAR) to apply a combination of the modified Hodge test plus EDTA synergy test on all K. pneumoniae clinical isolates obtained from February 2008 which displayed reduced susceptibility to carbapenems (MIC of imipenem > or = 1 mg/L). The presence of the blaKPC gene was confirmed by PCR and sequencing. This procedure revealed the presence of KPC-2 in isolates from 173 patients in 18 hospitals during a period of 11 months. Of these, 166 isolates belonged to a single pulsotype a fact consistent with possible epidemic spread, whereas the remaining seven isolates were further classified into four different pulsotypes. BlaKPC-2 gene was found to be transferable by conjugation in the four pulsotypes other than the prevailing one. The emergence of a new carbapenemase gene in Greece, where high resistance rates to carbapenems in K. pneumoniae due to the spread of the VIM type metalloenzyme have been observed, emphasises the urgent need for the implementation of public health measures in the field of infection control and antibiotic consumption. It also underlines the need to supplement surveillance systems based on susceptibility data with the surveillance of resistance mechanisms.
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PMID:KPC-2-producing Klebsiella pneumoniae infections in Greek hospitals are mainly due to a hyperepidemic clone. 1948 Aug 9


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