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Sample records for citrobacter freundii clinical

  1. Clinical features and antimicrobial susceptibility trends in Citrobacter freundii bacteremia.

    PubMed

    Chen, Ying-Sheng; Wong, Wing-Wai; Fung, Chang-Phone; Yu, Kwok-Woon; Liu, Cheng-Yi

    2002-06-01

    This retrospective study investigated the clinical characteristics and antimicrobial susceptibilities of 36 cases of Citrobacter freundii bacteremia treated at the Taipei Veterans General Hospital from 1996 through 1999. The results showed that the predominant infection site was the intraabdominal region and the mortality was 22%. The resistance of C. freundii to most third-generation cephalosporins and broad-spectrum penicillins increased in both nosocomial and community-acquired C. freundii bacteremia during the study period, and the strategy of using a combination of antimicrobial agents to treat C. freundii infection was effective. This study also demonstrated the importance of appropriate antimicrobial therapy to the successful outcome of C. freundii bacteremia. The guidelines of the National Nosocomial Infections Surveillance System were followed to determine trends of resistance of C. freundii to various antimicrobial agents. The resistance of C. freundii to antibiotics in 1999 (n = 10), compared with the period from 1996 through 1998 (n = 26), increased 66% for ciprofloxacin, 36% for ticarcillin/clavulanate, 70% for piperacillin/tazobactam, and 62.8% for piperacillin, but remained uniformly susceptible to imipenem/cilastatin and the new fluoroquinolone (levofloxacin). This increase in resistance was attributable to the use of third-generation cephalosporin instead of first-generation cephalosporins. These findings indicate the need for new measures to facilitate the appropriate choice of antimicrobial agents for patients with C. freundii bacteremia.

  2. Complete Genome of Citrobacter freundii Siphophage Stevie.

    PubMed

    Shaw, Justin P; Aviles Medina, Carlos A; Chen, Yi; Luna, Adrian J; Hernandez, Adriana C; Kuty Everett, Gabriel F

    2015-01-01

    Citrobacter freundii is an opportunistic pathogen responsible for many urinary tract infections acquired in hospitals and is thus a concern for public health. C. freundii phage Stevie might prove beneficial as a treatment against these infections. The complete genome of Stevie and its key features are described here.

  3. A new restriction endonuclease from Citrobacter freundii

    PubMed Central

    Janulaitis, A.A.; Stakenas, P.S.; Lebedenko, E.N.; Berlin, Yu.A.

    1982-01-01

    CfrI, a new restriction endonuclease of unique substrate specificity, has been isolated from a Citrobacter freundii strain. The enzyme recognizes a degenerated sequence PyGGCCPu in double-strand DNA and cleaves it between Py and G residues to yield 5′ -protruding tetranucleotide ends GGCC. Images PMID:6294607

  4. Genetic characteristics of blaNDM-1-positive plasmid in Citrobacter freundii isolate separated from a clinical infectious patient.

    PubMed

    Du, Xiao-Xing; Wang, Jian-Feng; Fu, Ying; Zhao, Feng; Chen, Yan; Wang, Hai-Ping; Yu, Yun-Song

    2013-09-01

    This study reports an infectious case involving an (NDM-1)-producing Citrobacter freundii and further explored the potential threat of the bla(NDM-1) gene by analysing the characteristics of the (NDM-1)-encoding plasmid sequence. A bla(NDM-1)-positive C. freundii with high resistance to carbapenems was separated from a clinical patient suffering from a urinary tract infection. S1 nuclease-based plasmid analysis followed by Southern blot hybridization, a conjugation experiment and electrotransformation confirmed that the bla(NDM-1) gene was located on a plasmid. High-throughput sequencing of the bla(NDM-1)-positive plasmid (pCFNDM-CN) showed that it was a 54 kb IncX-type plasmid and contained a backbone region and a variable region with two β-lactamase genes (bla(NDM-1) and bla(SHV-12)). The NDM-1 composite transposon in the variable region was surrounded by IS26 and IS5-truncated ISAba125, and shared a high sequence similarity to the bla(NDM-1) surrounding structure in Acinetobacter spp. Our research suggested that the NDM-1 composite transposon might play an essential role in mobilization of the bla(NDM-1) gene from Acinetobacter spp. to Enterobacteriaceae.

  5. Genetic characteristics of blaNDM-1-positive plasmid in Citrobacter freundii isolate separated from a clinical infectious patient.

    PubMed

    Du, Xiao-Xing; Wang, Jian-Feng; Fu, Ying; Zhao, Feng; Chen, Yan; Wang, Hai-Ping; Yu, Yun-Song

    2013-09-01

    This study reports an infectious case involving an (NDM-1)-producing Citrobacter freundii and further explored the potential threat of the bla(NDM-1) gene by analysing the characteristics of the (NDM-1)-encoding plasmid sequence. A bla(NDM-1)-positive C. freundii with high resistance to carbapenems was separated from a clinical patient suffering from a urinary tract infection. S1 nuclease-based plasmid analysis followed by Southern blot hybridization, a conjugation experiment and electrotransformation confirmed that the bla(NDM-1) gene was located on a plasmid. High-throughput sequencing of the bla(NDM-1)-positive plasmid (pCFNDM-CN) showed that it was a 54 kb IncX-type plasmid and contained a backbone region and a variable region with two β-lactamase genes (bla(NDM-1) and bla(SHV-12)). The NDM-1 composite transposon in the variable region was surrounded by IS26 and IS5-truncated ISAba125, and shared a high sequence similarity to the bla(NDM-1) surrounding structure in Acinetobacter spp. Our research suggested that the NDM-1 composite transposon might play an essential role in mobilization of the bla(NDM-1) gene from Acinetobacter spp. to Enterobacteriaceae. PMID:23741025

  6. Complete Genome Sequence of Citrobacter freundii Myophage Michonne.

    PubMed

    Bernal, Christopher L; Berkowitz, Victoria E; Cahill, Jesse L; Rasche, Eric S; Kuty Everett, Gabriel F

    2015-01-01

    Citrobacter freundii is a Gram-negative opportunistic pathogen that causes dangerous infections such as neonatal meningitis. C. freundii also harbors antibiotic resistance, making phages infecting this host valuable tools. Here, we announce the complete genome of the C. freundii FelixO1-like myophage Michonne and describe its notable features.

  7. Complete Genome Sequence of Citrobacter freundii Myophage Mordin.

    PubMed

    Guan, Jingwen; Snowden, Jeffrey D; Cahill, Jesse L; Rasche, Eric S; Kuty Everett, Gabriel F

    2015-01-01

    Citrobacter freundii is a Gram-negative opportunistic pathogen that is associated with urinary tract infections. Bacteriophages infecting C. freundii can be used as an effective treatment to fight these infections. Here, we announce the complete genome sequence of the C. freundii Felix O1-like myophage Mordin and describe its features.

  8. Complete Genome Sequence of Citrobacter freundii Myophage Mordin

    PubMed Central

    Guan, Jingwen; Snowden, Jeffrey D.; Cahill, Jesse L.; Rasche, Eric S.

    2015-01-01

    Citrobacter freundii is a Gram-negative opportunistic pathogen that is associated with urinary tract infections. Bacteriophages infecting C. freundii can be used as an effective treatment to fight these infections. Here, we announce the complete genome sequence of the C. freundii Felix O1-like myophage Mordin and describe its features. PMID:26472844

  9. Genetic Characterization of Atypical Citrobacter freundii

    PubMed Central

    Delgado, Gabriela; Souza, Valeria; Morales, Rosario; Cerritos, René; González-González, Andrea; Méndez, José Luis; Cravioto, Alejandro

    2013-01-01

    The ability of a bacterial population to survive in different niches, as well as in stressful and rapidly changing environmental conditions, depends greatly on its genetic content. To survive such fluctuating conditions, bacteria have evolved different mechanisms to modulate phenotypic variations and related strategies to produce high levels of genetic diversity. Laboratories working in microbiological diagnosis have shown that Citrobacter freundii is very versatile in its colony morphology, as well as in its biochemical, antigenic and pathogenic behaviours. This phenotypic versatility has made C. freundii difficult to identify and it is frequently confused with both Salmonella enterica and Escherichia coli. In order to determine the genomic events and to explain the mechanisms involved in this plasticity, six C. freundii isolates were selected from a phenotypic variation study. An I-CeuI genomic cleavage map was created and eight housekeeping genes, including 16S rRNA, were sequenced. In general, the results showed a range of both phenotypes and genotypes among the isolates with some revealing a greater similarity to C. freundii and some to S. enterica, while others were identified as phenotypic and genotypic intermediary states between the two species. The occurrence of these events in natural populations may have important implications for genomic diversification in bacterial evolution, especially when considering bacterial species boundaries. In addition, such events may have a profound impact on medical science in terms of treatment, course and outcomes of infectious diseases, evading the immune response, and understanding host-pathogen interactions. PMID:24069274

  10. Characterization of swarming motility in Citrobacter freundii.

    PubMed

    Cong, Yanguang; Wang, Jing; Chen, Zhijin; Xiong, Kun; Xu, Qiwang; Hu, Fuquan

    2011-04-01

    Bacterial swarming motility is a flagella-dependent translocation on the surface environment. It has received extensive attention as a population behavior involving numerous genes. Here, we report that Citrobacter freundii, an opportunistic pathogen, exhibits swarming movement on a solid medium surface with appropriate agar concentration. The swarming behavior of C. freundii was described in detail. Insertional mutagenesis with transposon Mini-Tn5 was carried out to discover genetic determinants related to the swarming of C. freundii. A number of swarming genes were identified, among which flhD, motA, motB, wzx, rfaL, rfaJ, rfbX, rfaG, rcsD, rcsC, gshB, fabF, dam, pgi, and rssB have been characterized previously in other species. In mutants related to lipopolysaccharide synthesis and RcsCDB signal system, a propensity to form poorly motile bacterial aggregates on the agar surface was observed. The aggregates hampered bacterial surface migration. In several mutants, the insertion sites were identified to be in the ORF of yqhC, yeeZ, CKO_03941, glgC, and ttrA, which have never been shown to be involved in swarming. Our results revealed several novel characteristics of swarming motility in C. freundii which are worthy of further study.

  11. Genetic characterization of atypical Citrobacter freundii.

    PubMed

    Delgado, Gabriela; Souza, Valeria; Morales, Rosario; Cerritos, René; González-González, Andrea; Méndez, José Luis; Vázquez, Virginia; Cravioto, Alejandro

    2013-01-01

    The ability of a bacterial population to survive in different niches, as well as in stressful and rapidly changing environmental conditions, depends greatly on its genetic content. To survive such fluctuating conditions, bacteria have evolved different mechanisms to modulate phenotypic variations and related strategies to produce high levels of genetic diversity. Laboratories working in microbiological diagnosis have shown that Citrobacter freundii is very versatile in its colony morphology, as well as in its biochemical, antigenic and pathogenic behaviours. This phenotypic versatility has made C. freundii difficult to identify and it is frequently confused with both Salmonella enterica and Escherichia coli. In order to determine the genomic events and to explain the mechanisms involved in this plasticity, six C. freundii isolates were selected from a phenotypic variation study. An I-CeuI genomic cleavage map was created and eight housekeeping genes, including 16S rRNA, were sequenced. In general, the results showed a range of both phenotypes and genotypes among the isolates with some revealing a greater similarity to C. freundii and some to S. enterica, while others were identified as phenotypic and genotypic intermediary states between the two species. The occurrence of these events in natural populations may have important implications for genomic diversification in bacterial evolution, especially when considering bacterial species boundaries. In addition, such events may have a profound impact on medical science in terms of treatment, course and outcomes of infectious diseases, evading the immune response, and understanding host-pathogen interactions.

  12. Complete Genome Sequence of Citrobacter freundii Myophage Merlin.

    PubMed

    LeSage, Kayla C; Hargrove, Emily C; Cahill, Jesse L; Rasche, Eric S; Kuty Everett, Gabriel F

    2015-01-01

    Bacteriophage Merlin is a T4-like myophage which infects Citrobacter freundii, a member of the Enterobacteriaceae family. C. freundii is an opportunistic pathogen that is a common cause of nosocomial infections. This report announces the complete genome of myophage Merlin and describes its features.

  13. Complete Genome Sequence of Citrobacter freundii Myophage Moogle.

    PubMed

    Nguyen, Quynh T; Luna, Adrian J; Hernandez, Adriana C; Kuty Everett, Gabriel F

    2015-01-01

    Citrobacter freundii is an opportunistic pathogen that has been linked to nosocomial infections, such as brain abscesses and pneumonia. Further study on phages infecting C. freundii may provide therapeutics for these infections. Here, we announce the complete genome sequence of the FelixO1-like myophage Moogle and describe its features.

  14. Complete Genome Sequence of Citrobacter freundii Myophage Moon.

    PubMed

    Edwards, Garrett B; Luna, Adrian J; Hernandez, Adriana C; Kuty Everett, Gabriel F

    2015-01-01

    Citrobacter freundii and other Gram-negative opportunistic pathogens necessitate concern from the public health sector. Bacteriophages that kill such pathogens may be useful in the control and containment of these infections. Here, we describe the genome of a newly isolated T4-like myophage of C. freundii, Moon, and present its features.

  15. Complete Genome Sequence of Citrobacter freundii Myophage Miller.

    PubMed

    Hwang, Kyuwon; Luna, Adrian J; Hernandez, Adriana C; Kuty Everett, Gabriel F

    2015-01-01

    Citrobacter freundii is a Gram-negative, opportunistic pathogen that can be fatal to newborns or immunocompromised patients. Bacteriophages against this bacterium can be useful for therapeutic purposes. Here, we describe the complete genome and the key features of the pseudo T-even C. freundii bacteriophage Miller.

  16. High prevalence of qnr and aac(6')-Ib-cr genes in both water-borne environmental bacteria and clinical isolates of Citrobacter freundii in China.

    PubMed

    Zhang, Rong; Ichijo, Tomoaki; Huang, Yong-Lu; Cai, Jia-Chang; Zhou, Hong-Wei; Yamaguchi, Nobuyasu; Nasu, Masao; Chen, Gong-Xiang

    2012-01-01

    We investigated the prevalence of qnr and aac(6')-Ib-cr genes in water-borne environmental bacteria and in clinical isolates of Enterobacteriaceae, as well as the subtypes of qnr. Environmental bacteria were isolated from surface water samples obtained from 10 different locations in Hangzhou City, and clinical isolates of Citrobacter freundii were isolated from several hospitals in four cities in China. qnrA, qnrB, qnrS, and aac(6')-Ib-cr genes were screened using PCR, and the genotypes were analyzed by DNA sequencing. Ten of the 78 Gram-negative bacilli isolated from water samples were C. freundii and 80% of these isolates carried the qnrB gene. qnrS1 and aac(6')-Ib-cr genes were detected in two Escherichia coli isolates and qnrS2 was detected in one species, Aeromonas punctata. The qnr and aac(6')-Ib-cr genes were present in 75 (72.8%) and 12 (11.6%) of 103 clinical isolates of C. freundii, respectively. Of the clinical C. freundii isolates with the qnr gene, 65 isolates (63.1%) carried qnrB, but only three (2.9%) and one (1.0%) carried qnrA1 and qnrS2, respectively, while five isolates carried both qnrA1 and qnrB, and one isolate carried both qnrS1 and qnrB. The qnrB9 gene was the dominant qnrB subtype, followed by qnrB8 and qnrB6. Southern hybridization studies indicated that the qnr genes are located on different plasmids. Plasmids isolated from both environmental and clinical C. freundii isolates appeared to be homogenous.

  17. Bacteraemia caused by non-freundii, non-koseri Citrobacter species in Taiwan.

    PubMed

    Lai, C-C; Tan, C-K; Lin, S-H; Liu, W-L; Liao, C-H; Huang, Y-T; Hsueh, P-R

    2010-12-01

    This study analysed the clinical characteristics of bacteraemia due to unusual Citrobacter species. All non-freundii and non-koseri Citrobacter isolates were identified to species level by two commercial identification methods and 16S rRNA gene sequence analysis. A total of 306 patients with Citrobacter spp. bacteraemia were identified from January 2000 through December 2009. Four patients (1.3%) had C. braakii bacteraemia, and one had C. amalonaticus and C. sedlakii sepsis, respectively. Misidentification as non-freundii and non-koseri Citrobacter spp., which occurred in eight isolates with the Phoenix automated system PMIC/ID-30 and three with the Vitek II system, occurred in five of six infection episodes. Among the six patients with bacteraemia caused by non-freundii and non-koseri Citrobacter spp., five (83.3%) had healthcare-associated infection and five (83.3%) infections were secondary to intra-abdominal infection. Cancer and liver cirrhosis were the commonest underlying diseases. An attributable mortality was 33.3%. Antimicrobial susceptibility testing showed that the resistance patterns varied among different Citrobacter species. Non-freundii and non-koseri Citrobacter species are difficult to identify and are a rare cause of intra-abdominal infections with secondary healthcare-associated bacteraemia in immunocompromised patients.

  18. Draft Genome Sequence of the Type Species of the Genus Citrobacter, Citrobacter freundii MTCC 1658.

    PubMed

    Kumar, Shailesh; Kaur, Chandandeep; Kimura, Kazuyuki; Takeo, Masahiro; Raghava, Gajendra Pal Singh; Mayilraj, Shanmugam

    2013-01-01

    We report the 5.0-Mb genome sequence of the type species of the genus Citrobacter, Citrobacter freundii strain MTCC 1658, isolated from canal water. This draft genome sequence of C. freundii strain MTCC 1658(T) consists of 5,001,265 bp with a G+C content of 51.61%, 4,691 protein-coding genes, 70 tRNAs, and 10 rRNAs.

  19. Characterization of a virulent bacteriophage LK1 specific for Citrobacter freundii isolated from sewage water.

    PubMed

    Chaudhry, Waqas Nasir; Haq, Irshad Ul; Andleeb, Saadia; Qadri, Ishtiaq

    2014-06-01

    Citrobacter freundii is a worldwide emerging nosocomial pathogen with escalating incidence of multidrug resistance. Citrobacter freundii exists in natural environment, especially in health care settings and is difficult to eradicate. Phage therapy is considered as an alternative way of controlling bacterial infections and contaminations. In this study, we have described isolation and characterization of a virulent bacteriophage LK1 capable of specifically infecting Citrobacter freundii. A virulent bacteriophage LK1, specific for Citrobacter freundii was isolated from sewage water sample. TEM showed that phage Lk1 has an icosahedral head 70 nm in diameter and short tail of 17 nm, and can be classified as a member of the Podoviridae family. Restriction analysis indicated that phage LK1 was a dsDNA virus with an approximate genome size of 20-23 kb. Proteomic pattern generated by SDS PAGE using purified LK1 phage particles, revealed three major and six minor protein bands with molecular weight ranging from 25 to 80 kDa. Adsorption rate of LK1 relative to the host bacterium was also determined which showed significant improvement in adsorption with the addition of CaCl2 . In a single step growth experiment, LK1 exhibited a latent period of 24 min and burst size of 801 particle/cell. Moreover, pH and thermal stability of phage LK1 demonstrated a pH range of 5.0-6.0 and phage viability decreased to 0% at 65 °C. When LK1 was used to infect six other clinically isolated pathogenic strains, it showed relatively narrow host range. LK1 was capable of eliciting efficient lysis of Citrobacter freundii, revealing its potential as a non-toxic sanitizer for controlling Citrobacter freundii infection and contamination in both hospital and other public environments.

  20. Comparison of antimicrobial susceptibility of Citrobacter freundii isolates in two different time periods.

    PubMed

    Wang, J T; Chang, S C; Chen, Y C; Luh, K T

    2000-12-01

    Citrobacter freundii was first identified in 1932, since then it has been reported to cause a variety of infections in aged, immunocompromised, and debilitated patients. With the use of broad-spectrum antibiotics, C. freundii has become increasingly resistant to antimicrobial agents. In order to determine the chronological changes in susceptibility and current susceptibility status of C. freundii, we compared the antimicrobial susceptibility of C. freundii in two different time periods, from 1987 to 1988 and from 1997 to 1998. In both time periods, 61 isolates of C. freundii were randomly selected for study from all clinical isolates at National Taiwan University Hospital. The minimum inhibitory concentrations and susceptible rates of 15 antimicrobial agents were compared, and it was found that most C. freundii isolates were resistant to anti-pseudomonal penicillins, first, second, and third generation cephalosporins, gentamicin, tobramycin, and aztreonam. The results indicate that the susceptible rates of C. freundii to aminoglycosides and ciprofloxacin decreased markedly during the period from 1987 to 1998. Cefepime, cefpirome, imipenem, and meropenem remained the most active agents against C. freundii.

  1. Genome sequencing, annotation of Citrobacter freundii strain GTC 09479.

    PubMed

    Kimura, Kazuyuki; Kumar, Shailesh; Takeo, Masahiro; Mayilraj, Shanmugam

    2014-12-01

    We report the 4.9-Mb genome sequence of Citrobacter freundii strain GTC 09479, isolated from urine sample collected during the year 1983 at Gifu University Graduate School of Medicine, Japan. This draft genome consist of 4,899,578 bp with 51.62% G + C, 4,574 predicted CDSs, 72 tRNAs and 10 rRNAs.

  2. Thermolabile repression of cephalosporinase synthesis in Citrobacter freundii.

    PubMed

    Sawai, T; Nakajima, S; Morohoshi, T; Yamagishi, S

    1977-11-01

    An unusual regulatory system of cephalosporinase synthesis in Citrobacter freundii has been found. When the bacteria are grown at 20 C, the cephalosporinase is synthesized as a typical inducible enzyme and benzylpenicillin acts as an effective inducer. The enzyme, however, is synthesized in the absence of the inducer at growth temperatures above 25 C. when the growth temperature is shifted from 20 C to 37 C, the induction of enzyme synthesis is observed after about one half of the organism doubling time, but it does not occur in the presence of chloramphenicol. The reverse control mutants, the enzyme constitutive synthesis of which is markedly depressed by benzylpenicillin, were isolated from the C. freundii wild strain. The possibility that the enzyme synthesis is governed by a regulatory system analogous to the its mutant of the lac operon in Escherichia coli was suggested. PMID:203825

  3. High-level carbapenem resistance in a Citrobacter freundii clinical isolate is due to a combination of KPC-2 production and decreased porin expression.

    PubMed

    Zhang, Rong; Yang, Lijiang; Cai, Jia Chang; Zhou, Hong Wei; Chen, Gong-Xiang

    2008-03-01

    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.

  4. Emergence of a cefepime- and cefpirome-resistant Citrobacter freundii clinical isolate harbouring a novel chromosomally encoded AmpC beta-lactamase, CMY-37.

    PubMed

    Ahmed, Ashraf M; Shimamoto, Tadashi

    2008-09-01

    Citrobacter freundii strain 4306 was isolated from a urine specimen of a patient in March 2006 in Palestine. This strain showed a unique multidrug resistance phenotype, as it was resistant both to 7-alpha-methoxy- and oxyimino-cephalosporins, including cefepime, cefpirome and monobactams, in addition to quinolones, streptomycin and trimethoprim/sulfamethoxazole. Clavulanic acid did not act synergistically with cephalosporins by the double-disk synergy test. Molecular characterisation showed that the resistance to 7-alpha-methoxy- and oxyimino-cephalosporins was due to a novel AmpC beta-lactamase, designated CMY-37, with an isoelectric point of approximately 9.0. CMY-37 is a variant of C. freundii chromosomal AmpC enzymes with at least seven amino acid substitutions. One of these substitutions, L316I, is located within the R2 loop that is considered the hotspot region responsible for the extended substrate spectrum in class C beta-lactamases. The blaCMY-37 gene was cloned and expressed in Escherichia coli TG1. CMY-37 is chromosomally encoded and is not associated with ISEcp1-like element. Phylogenetic analysis suggested that CMY-37 is the origin of many plasmid-mediated AmpC beta-lactamases. This study highlights the emergence of cefepime and cefpirome resistance in C. freundii owing to a new type of AmpC beta-lactamase.

  5. Isolation and characterization of cytotoxic, aggregative Citrobacter freundii.

    PubMed

    Bai, Li; Xia, Shengli; Lan, Ruiting; Liu, Liyun; Ye, Changyun; Wang, Yiting; Jin, Dong; Cui, Zhigang; Jing, Huaiqi; Xiong, Yanwen; Bai, Xuemei; Sun, Hui; Zhang, Jin; Wang, Lei; Xu, Jianguo

    2012-01-01

    Citrobacter freundii is an infrequent but established cause of diarrhea in humans. However, little is known of its genetic diversity and potential for virulence. We analyzed 26 isolates, including 12 from human diarrheal patients, 2 from human fecal samples of unknown diarrheal status, and 12 from animals, insects, and other sources. Pulsed field gel electrophoresis using XbaI allowed us to divide the 26 isolates into 20 pulse types, while multi-locus sequence typing using 7 housekeeping genes allowed us to divide the 26 isolates into 6 sequence types (STs) with the majority belonging to 4 STs. We analyzed adhesion and cytotoxicity to HEp-2 cells in these 26 strains. All were found to adhere to HEp-2 cells. One strain, CF74, which had been isolated from a goat, showed the strongest aggregative adhesion pattern. Lactate dehydrogenase (LDH) released from HEp-2 cells was evaluated as a measure of cytotoxicity, averaging 7.46%. Strain CF74 induced the highest level of LDH, 24.3%, and caused >50% cell rounding, detachment, and death. We named strain CF74 "cytotoxic and aggregative C. freundii." Genome sequencing of CF74 revealed that it had acquired 7 genomic islands, including 2 fimbriae islands and a type VI secretion system island, all of which are potential virulence factors. Our results show that aggregative adherence and cytotoxicity play an important role in the pathogenesis of C. freundii.

  6. Origin and evolution of the AmpC beta-lactamases of Citrobacter freundii.

    PubMed

    Barlow, Miriam; Hall, Barry G

    2002-05-01

    To determine whether the widespread clinical use of beta-lactams has been selective for Citrobacter freundii-derived alleles of plasmid ampC genes, we generated a Bayesian consensus phylogeny of the published ampC sequences and compared the MICs of 16 beta-lactam antibiotics for Escherichia coli strains containing cloned copies of the C. freundii ampC alleles. We found that for the majority of compounds investigated, there has been essentially no increase in beta-lactam resistance conferred by those alleles. We also found that ampC alleles from the chromosomes of two beta-lactam-sensitive C. freundii strains isolated in the 1920s, before the clinical use of antibiotics, were as effective at providing beta-lactam resistance in E. coli as were the plasmid-borne alleles from beta-lactam-resistant clinical isolates. These results suggest that selection for increased resistance to beta-lactam antibiotics has not been a significant force directing the evolution of the C. freundii ampC alleles found in beta-lactam-resistant clinical isolates.

  7. Isolation of a Citrobacter freundii strain which carries the Escherichia coli O157 antigen.

    PubMed Central

    Bettelheim, K A; Evangelidis, H; Pearce, J L; Sowers, E; Strockbine, N A

    1993-01-01

    A biochemically typical strain of Citrobacter freundii which carries the Escherichia coli O157 antigen is described. The significance of differentiating such strains from typical E. coli O157 strains is stressed. PMID:7681442

  8. Purification and characterization of tyrosine phenol lyase from Citrobacter freundii.

    PubMed

    Chandel, Meenakshi; Azmi, Wamik

    2013-12-01

    The purification and characterization of intracellular tyrosine phenol lyase from Citrobacter freundii has been carried out. The enzyme was purified 35-fold to homogeneity by ammonium sulphate precipitation and hydrophobic interaction chromatography. Its subunit molecular weight was found to be 52 kDa on sodium dodecyl sulphate polyacrylamide gel electrophoresis. The purified tyrosine phenol lyase showed maximum activity in borate buffer (0.05 M at pH 8.5) at 45 °C after 20 min of incubation. The Km and Vmax values of purified enzyme were found to be 0.446 mm and 0.342 mM/min/mg. This enzyme exhibits t1/2 of 10, 52 and 130 min at 55, 45 and 35 °C, respectively. The N-terminal amino acid sequence was determined as MET-ASN-TYR-PRO-ALA-GLU-PRO-PHE-ARG-ILETRP- TRP-VAL-GLY.

  9. Severe peritonitis caused by Citrobacter freundii and successful treatment with double antibiotic coverage.

    PubMed

    Kataria, A; Saad, E

    2015-01-01

    Serratia, Pseudomonas/Providencia, indole-positive Proteus/Acinetobacter/Morganella, Citrobacter, Enterobacter and Hafnia group of organisms cause peritoneal dialysis (PD)-related peritonitis with high morbidity and mortality. Peritonitis caused by Citrobacter freundii is uncommon, and it may lead to catheter removal despite antimicrobial treatment. We describe a case of PD-related peritonitis caused by C. freundii, which was successfully treated with double antibiotic coverage.

  10. Characterization of Five Podoviridae Phages Infecting Citrobacter freundii

    PubMed Central

    Hamdi, Sana; Rousseau, Geneviève M.; Labrie, Simon J.; Kourda, Rim S.; Tremblay, Denise M.; Moineau, Sylvain; Slama, Karim B.

    2016-01-01

    Citrobacter freundii causes opportunistic infections in humans and animals, which are becoming difficult to treat due to increased antibiotic resistance. The aim of this study was to explore phages as potential antimicrobial agents against this opportunistic pathogen. We isolated and characterized five new virulent phages, SH1, SH2, SH3, SH4, and SH5 from sewage samples in Tunisia. Morphological and genomic analyses revealed that the five C. freundii phages belong to the Caudovirales order, Podoviridae family, and Autographivirinae subfamily. Their linear double-stranded DNA genomes range from 39,158 to 39,832 bp and are terminally redundant with direct repeats between 183 and 242 bp. The five genomes share the same organization as coliphage T7. Based on genomic comparisons and on the phylogeny of the DNA polymerases, we assigned the five phages to the T7virus genus but separated them into two different groups. Phages SH1 and SH2 are very similar to previously characterized phages phiYeO3-12 and phiSG-JL2, infecting, respectively, Yersinia enterocolitica and Salmonella enterica, as well as sharing more than 80% identity with most genes of coliphage T7. Phages SH3, SH4, and SH5 are very similar to phages K1F and Dev2, infecting, respectively, Escherichia coli and Cronobacter turicensis. Several structural proteins of phages SH1, SH3, and SH4 were detected by mass spectrometry. The five phages were also stable from pH 5 to 10. No genes coding for known virulence factors or integrases were found, suggesting that the five isolated phages could be good candidates for therapeutic applications to prevent or treat C. freundii infections. In addition, this study increases our knowledge about the evolutionary relationships within the T7virus genus. PMID:27446058

  11. Characterization of Five Podoviridae Phages Infecting Citrobacter freundii.

    PubMed

    Hamdi, Sana; Rousseau, Geneviève M; Labrie, Simon J; Kourda, Rim S; Tremblay, Denise M; Moineau, Sylvain; Slama, Karim B

    2016-01-01

    Citrobacter freundii causes opportunistic infections in humans and animals, which are becoming difficult to treat due to increased antibiotic resistance. The aim of this study was to explore phages as potential antimicrobial agents against this opportunistic pathogen. We isolated and characterized five new virulent phages, SH1, SH2, SH3, SH4, and SH5 from sewage samples in Tunisia. Morphological and genomic analyses revealed that the five C. freundii phages belong to the Caudovirales order, Podoviridae family, and Autographivirinae subfamily. Their linear double-stranded DNA genomes range from 39,158 to 39,832 bp and are terminally redundant with direct repeats between 183 and 242 bp. The five genomes share the same organization as coliphage T7. Based on genomic comparisons and on the phylogeny of the DNA polymerases, we assigned the five phages to the T7virus genus but separated them into two different groups. Phages SH1 and SH2 are very similar to previously characterized phages phiYeO3-12 and phiSG-JL2, infecting, respectively, Yersinia enterocolitica and Salmonella enterica, as well as sharing more than 80% identity with most genes of coliphage T7. Phages SH3, SH4, and SH5 are very similar to phages K1F and Dev2, infecting, respectively, Escherichia coli and Cronobacter turicensis. Several structural proteins of phages SH1, SH3, and SH4 were detected by mass spectrometry. The five phages were also stable from pH 5 to 10. No genes coding for known virulence factors or integrases were found, suggesting that the five isolated phages could be good candidates for therapeutic applications to prevent or treat C. freundii infections. In addition, this study increases our knowledge about the evolutionary relationships within the T7virus genus.

  12. Characterization of Five Podoviridae Phages Infecting Citrobacter freundii.

    PubMed

    Hamdi, Sana; Rousseau, Geneviève M; Labrie, Simon J; Kourda, Rim S; Tremblay, Denise M; Moineau, Sylvain; Slama, Karim B

    2016-01-01

    Citrobacter freundii causes opportunistic infections in humans and animals, which are becoming difficult to treat due to increased antibiotic resistance. The aim of this study was to explore phages as potential antimicrobial agents against this opportunistic pathogen. We isolated and characterized five new virulent phages, SH1, SH2, SH3, SH4, and SH5 from sewage samples in Tunisia. Morphological and genomic analyses revealed that the five C. freundii phages belong to the Caudovirales order, Podoviridae family, and Autographivirinae subfamily. Their linear double-stranded DNA genomes range from 39,158 to 39,832 bp and are terminally redundant with direct repeats between 183 and 242 bp. The five genomes share the same organization as coliphage T7. Based on genomic comparisons and on the phylogeny of the DNA polymerases, we assigned the five phages to the T7virus genus but separated them into two different groups. Phages SH1 and SH2 are very similar to previously characterized phages phiYeO3-12 and phiSG-JL2, infecting, respectively, Yersinia enterocolitica and Salmonella enterica, as well as sharing more than 80% identity with most genes of coliphage T7. Phages SH3, SH4, and SH5 are very similar to phages K1F and Dev2, infecting, respectively, Escherichia coli and Cronobacter turicensis. Several structural proteins of phages SH1, SH3, and SH4 were detected by mass spectrometry. The five phages were also stable from pH 5 to 10. No genes coding for known virulence factors or integrases were found, suggesting that the five isolated phages could be good candidates for therapeutic applications to prevent or treat C. freundii infections. In addition, this study increases our knowledge about the evolutionary relationships within the T7virus genus. PMID:27446058

  13. Citrobacter freundii septicemia in a stranded newborn Cuvier's beaked whale (Ziphius cavirostris).

    PubMed

    Fernández, Antonio; Vela, Ana Isabel; Andrada, Marisa; Herraez, Pedro; Díaz-Delgado, Josue; Domínguez, Lucas; Arbelo, Manuel

    2011-10-01

    Citrobacter freundii, a gram-negative enterobacterium, may cause fatal septicemia in humans and animals. Its potential pathogenic role in cetaceans (bottlenose dolphins and beluga whales) has been hypothesized. Here we describe fatal C. freundii septicemia in a stranded newborn Cuvier's beaked whale (Ziphius cavirostris). PMID:22102682

  14. Citrobacter freundii septicemia in a stranded newborn Cuvier's beaked whale (Ziphius cavirostris).

    PubMed

    Fernández, Antonio; Vela, Ana Isabel; Andrada, Marisa; Herraez, Pedro; Díaz-Delgado, Josue; Domínguez, Lucas; Arbelo, Manuel

    2011-10-01

    Citrobacter freundii, a gram-negative enterobacterium, may cause fatal septicemia in humans and animals. Its potential pathogenic role in cetaceans (bottlenose dolphins and beluga whales) has been hypothesized. Here we describe fatal C. freundii septicemia in a stranded newborn Cuvier's beaked whale (Ziphius cavirostris).

  15. Characterization of the Citrobacter freundii phoE gene and development of C. freundii-specific oligonucleotides.

    PubMed

    Spierings, G; Ockhuijsen, C; Hofstra, H; Tommassen, J

    1992-12-01

    The phoE gene of Citrobacter freundii, encoding a pore-forming outer membrane protein, was cloned and its nucleotide sequence was determined. The homologies in terms of identical amino acids between the C. freundii PhoE protein and those of Escherichia coli, E. cloacae and Klebsiella pneumoniae were 90%, 86% and 84%, respectively. Two synthetic oligonucleotides, corresponding to hypervariable, cell surface-exposed regions of the protein, were tested for their specificity in polymerase chain reactions. They were specific for the species C. freundii, i.e., no reaction was detected with 35 non-C. freundii strains tested, including 17 Salmonella, two C. amalonaticus and three C. diversus strains, whereas all five C. freundii strains tested were correctly recognized.

  16. Bacteriophage lytic patterns for identification of salmonellae, shigellae, Escherichia coli, Citrobacter freundii, and Enterobacter cloacae.

    PubMed

    He, X Q; Pan, R N

    1992-03-01

    A series of bacteriophages specific for Escherichia coli (E-1, E-2, E-3, and E-4), Citrobacter freundii (phi I, phi II, and phi III), Enterobacter cloacae (Ent), and Shigella spp. (Sh) have been isolated from hospital sewage. These bacteriophages, in combination with Felix Salmonella phage O-I, were used as a diagnostic phage typing set which included seven phage preparations: O-I, C (phi I and phi III), Sh, E (E-1 and E-2), CE (phi II and E-3), E-4, and Ent. After 20,280 cultures of 27 species and 9 biogroups of 15 genera of the family Enterobacteriaceae and 276 cultures of 8 species of 6 genera outside the Enterobacteriaceae were tested, it was shown that most strains of salmonellae, E. coli, C. freundii, and E. cloacae can be identified accurately. The sensitivities of identification were 83.6% for E. cloacae, 88.8% for C. freundii, 90.3% for E. coli, and 95.76% for salmonellae. The specificities were 99.78% for salmonellae, 99.84% for E. cloacae, 99.89% for E. coli, and 99.97% for C. freundii. The results of bacteriophage lytic patterns were highly correlated with Shigella serotypes. Therefore, such a phage typing set may be used routinely in public hygiene and clinical laboratories.

  17. Production of methionine γ- lyase in recombinant Citrobacter freundii bearing the hemoglobin gene.

    PubMed

    Kahraman, Huseyin; Aytan, Emel; Kurt, Ash Giray

    2011-09-01

    The production of antileukemic enzyme methionine γ-lyase (MGL) in distinctly related bacteria, Citrobacter freundii and in their recombinants expressing the Vitresocilla hemoglobin (VHb) has been studied. This study concerns the potential of Citrobacter freundii expressing the Vitreoscilla hemoglobin gene (vgb) for the methionine γ- liyase production. Methionine γ- liyase production by Citrobacter freundii and its vgb(-) and vgb(+) bearing recombinant strain was studied in shake-flasks under 200 rpm agitation, culture medium and 30 °C in a time-course manner. The vgb(+) and especially the carbon type had a dramatic effect on methionine γ- liyase production. The vgb(+) strain of C. freundii had about 2-fold and 3.1-fold higher levels of MGL than the host and vgb(-) strain, respectively.

  18. Citrobacter freundii invades and replicates in human brain microvascular endothelial cells.

    PubMed

    Badger, J L; Stins, M F; Kim, K S

    1999-08-01

    Neonatal bacterial meningitis remains a disease with unacceptable rates of morbidity and mortality despite the availability of effective antimicrobial therapy. Citrobacter spp. cause neonatal meningitis but are unique in their frequent association with brain abscess formation. The pathogenesis of Citrobacter spp. causing meningitis and brain abscess is not well characterized; however, as with other meningitis-causing bacteria (e.g., Escherichia coli K1 and group B streptococci), penetration of the blood-brain barrier must occur. In an effort to understand the pathogenesis of Citrobacter spp. causing meningitis, we have used the in vitro blood-brain barrier model of human brain microvascular endothelial cells (HBMEC) to study the interaction between C. freundii and HBMEC. In this study, we show that C. freundii is capable of invading and trancytosing HBMEC in vitro. Invasion of HBMEC by C. freundii was determined to be dependent on microfilaments, microtubules, endosome acidification, and de novo protein synthesis. Immunofluorescence microscopy studies revealed that microtubules aggregated after HBMEC came in contact with C. freundii; furthermore, the microtubule aggregation was time dependent and seen with C. freundii but not with noninvasive E. coli HB101 and meningitic E. coli K1. Also in contrast to other meningitis-causing bacteria, C. freundii is able to replicate within HBMEC. This is the first demonstration of a meningitis-causing bacterium capable of intracellular replication within BMEC. The important determinants of the pathogenesis of C. freundii causing meningitis and brain abscess may relate to invasion of and intracellular replication in HBMEC.

  19. Phosphatase production and activity in Citrobacter freundii and a naturally occurring, heavy-metal-accumulating Citrobacter sp.

    PubMed

    Montgomery, D M; Dean, A C; Wiffen, P; Macaskie, L E

    1995-10-01

    The ability of a naturally occurring Citrobacter sp. to accumulate cadmium has been attributed to cellular precipitation of CdHPO4, utilizing HPO4(2-) liberated via the activity of an overproduced, Cd-resistant acid-type phosphatase. Phosphatase production and heavy metal accumulation by batch cultures of this strain (N14) and a phosphatase-deficient mutant were compared with two reference strains of Citrobacter freundii. Only strain N14 expressed a high level of acid phosphatase and accumulated lanthanum and uranyl ion enzymically. Acid phosphatase is regulated via carbon-starvation; although the C. freundii strains overexpressed phosphatase activity in carbon-limiting continuous culture, this was approximately 20-fold less than the activity of strain N14 grown similarly. Citrobacter strain N14 was originally isolated from a metal-contaminated soil environment; phosphatase overproduction and metal accumulation were postulated as a detoxification mechanism. However, application of Cd-stress, and enrichment for Cd-resistant C. freundii ('training'), reduced the phosphatase activity of this organism by about 50% as compared to Cd-unstressed cultures. The acid phosphatase of C. freundii and Citrobacter N14 had a similar pattern of resistance to some diagnostic reagents. The enzyme of the latter is similar to the PhoN acid phosphatase of Salmonella typhimurium described by other workers; the results are discussed with respect to the known phosphatases of the enterobacteria.

  20. Characterization of an extended-spectrum class C beta-lactamase of Citrobacter freundii.

    PubMed

    Haruta, S; Nukaga, M; Sawai, T

    2001-01-01

    Citrobacter freundii GC3 is a clinical isolate which showed moderate resistance to oxyimino beta-lactams such as ceftazidime and aztreonam. This drug resistance was due to an extended-spectrum class C beta-lactamase encoded by chromosomal gene(s). The GC3 beta-lactamase showed high amino acid sequence homology to a known C. freundii beta-lactamase, i.e., 346 of 361 amino acids were identical with those of C. freundii GN346 beta-lactamase (Tsukamoto, K. et al, Eur. J. Biochem. 188, 15-22, 1990). Asp198 was the only dissimilar amino acid found in the omega loop region, known as the hot spot for extended-spectrum resistance in class C beta-lactamases (Haruta, S. et al, Microbiol. Immunol. 42, 165-169, 1998). However, Asp198 was eliminated as a cause of the extended-spectrum resistance by the substitution of Asn for Asp198. Subsequent investigation suggested that the moderate resistance to oxyimino beta-lactams is attributable to the replacement of amino acids on the enzyme's surface area, far from the active-site. Some or all of the replacements are assumed to delicately modify the active-site configuration. The GC3 beta-lactamase is the first example of an extended-spectrum class C beta-lactamase in which mutations are independent of the omega loop.

  1. Genetic regulation of variable Vi antigen expression in a strain of Citrobacter freundii.

    PubMed

    Snellings, N J; Johnson, E M; Kopecko, D J; Collins, H H; Baron, L S

    1981-02-01

    Certain strains of the genus Citrobacter exhibit a variable expression of the Vi surface antigen that appears to involve a special mechanism for regulation of gene expression. Two nonlinked chromosomal loci, viaA and viaB, are known to determine nonvariable Vi antigen expression in strains of Salmonella. To confirm the presence of analogous loci in Citrobacter and to ascertain whether either of them is involved in variable Vi antigen expression in this organism, donor strains were constructed from Citrobacter freundii WR7004 and used to transfer their Vi antigen-determining genes to ViaA- and ViaB- Salmonella typhi recipient strains. Vi antigen expression in C. freundii was found to be controlled by loci analogous to the Salmonella via genes. S. typhi recipients of the C. freundii viaA+ genes were restored to the full, continuous expression of the Vi antigen normally seen in S. typhi. Thus, the C. freundii viaA genes appeared to play no role in the variable expression of the Vi antigen. In contrast, S. typhi recipients of the C. freundii viaB+ genes exhibited the rapid, reversible alternation between full Vi antigen expression and markedly reduced Vi antigen expression that was seen to occur in the C. freundii parent. The C. freundii viaB locus was thus identified as the one whose genes are regulated so as to produce variable Vi antigen expression. Genes determining another C. freundii surface antigen, the synthesis of which is not affected by the mechanism regulating Vi expression, were coinherited with the C. freundii viaB+ genes. An invertible, insertion sequence element located within the C. freundii viaB locus is proposed to account for the regulation of variable Vi antigen expression.

  2. Morphological alterations on Citrobacter freundii bacteria induced by erythrosine dye and laser light.

    PubMed

    Silva, Josmary R; Cardoso, Gleidson; Maciel, Rafael R G; de Souza, Nara C

    2015-01-01

    The effect of the laser irradiation (532 nm) on films prepared from Citrobacter freundii mixed with erythrosine dye was investigated by using atomic force microscopy. It was observed that morphological changes of bacterial surfaces after irradiations, which were attributed to cellular damage of the outer membranes, are a result of a photodynamic effect. The results suggested that the combination of erythrosine and laser light at 532 nm could be a candidate to a photodynamic therapy against C. freundii.

  3. Characterization of phiCFP-1, a virulent bacteriophage specific for Citrobacter freundii.

    PubMed

    Zhao, Xiangna; Huang, Simo; Zhao, Jiangtao; He, Xiaoming; Li, Erna; Li, Huan; Liu, Wei; Zou, Dayang; Wei, Xiao; Wang, Xuesong; Dong, Derong; Yang, Zhan; Yan, Xiabei; Shen, Zhiqiang; Yuan, Jing

    2016-05-01

    Citrobacter freundii, a Gram-negative bacterium, causes many opportunistic infections. Bacteriophage phiCFP-1 was isolated and characterized by its ability to lyse the multidrug-resistant clinical C. freundii strain P10159. Transmission electron microscopy showed that the phage has an icosahedral head and a short tail, making it a Podoviridae family member. In a single-step growth experiment, phiCFP-1 exhibited an eclipse period of 20 min and a burst size of 100 particles per cell. Its genome assembled as a circular molecule when genomic sequencing was completed. However, based on genome content and organization, it was categorized as a classic T7-related phage, and such phages are known to have linear genomes with direct terminal repeats. With the quick and simple method established herein, the 38,625-bp linear double-stranded DNA with 229-bp direct terminal repeats was accurately identified. The genome contained 43 putative open reading frames and no tRNA genes. Using a proteomics-based approach, seven viral and two host proteins from purified phiCFP-1 particles were identified. Comparative genomics and recombination analyzes revealed close genetic relatedness among phiCFP-1, phiYeO3-12/vB_YenP_AP5 (from Yersinia enterocolitica O3), and phiSG-JL2 (from Salmonella enterica).

  4. Utilization of aminoaromatic acids by a methanogenic enrichment culture and by a novel Citrobacter freundii strain.

    PubMed

    Savelieva, Olga; Kotova, Irina; Roelofsen, Wim; Stams, Alfons J M; Netrusov, Alexander

    2004-02-01

    Following incubation of mesophilic methanogenic floccular sludge from a lab-scale upflow anaerobic sludge bed reactor used to treat cattle manure wastewater, a stable 5-aminosalicylate-degrading enrichment culture was obtained. Subsequently, a Citrobacter freundii strain, WA1, was isolated from the 5-aminosalicylate-degrading methanogenic consortium. The methanogenic enrichment culture degraded 5-aminosalicylate completely to CH4, CO2 and NH4+, while C. freundii strain WA1 reduced 5-aminosalicylate with simultaneous deamination to 2-hydroxybenzyl alcohol during anaerobic growth with electron donors such as pyruvate, glucose or serine. When grown on pyruvate, C. freundii WA1 converted 3-aminobenzoate to benzyl alcohol and also reduced benzaldehyde to benzyl alcohol. Pyruvate was fermented to acetate, CO2, H2 and small amounts of lactate, succinate and formate. Less lactate (30%) was produced from pyruvate when C. freundii WA1 grew with 5-aminosalicylate as co-substrate.

  5. Prevalence of decreased susceptibility to carbapenems among Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii and investigation of carbapenemases.

    PubMed

    Lee, Hae Kyung; Park, Yeon-Joon; Kim, Ja-Young; Chang, Eundeok; Cho, Seok Goo; Chae, Hiun Suk; Kang, Chang Suk

    2005-08-01

    Between March and July 2002, total of 612 clinical isolates of Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii (201 S. marcescens, 228 E. cloacae, and 183 C. freundii) were collected from 13 clinical laboratories in a nationwide distribution. Imipenem and meropenem minimum inhibitory concentrations (MICs) were determined using the agar dilution method according to the National Committee for Clinical Laboratory Standards guidelines. For the isolates with a decreased susceptibility to carbapenems (MICs of >or=2 microg/mL), isoelectric focusing, polymerase chain reaction (PCR) amplification of the carbapenemase genes (bla(IMP-1), bla(VIM-2), bla(SME-1), bla(OXA-23), bla(OXA-25), bla(KPC-1)), and sequencing were performed. The prevalence of S. marcescens, E. cloacae, and C. freundii with a decreased susceptibility to imipenem was 17.9% (36/201), 0.4% (1/228), and 0.5% (1/183), respectively, and to meropenem, it was 11.4% (23/201), 0% (0/228), and 0.5% (1/183), respectively. The bla(VIM-2) was the only carbapenemase detected, and was found in 0.5% (1/201) of S. marcescens and 0.5% (1/183) of C. freundii isolate.

  6. Decreased production of AmpC-type beta-lactamases associated with the development of resistance to quinolones in Citrobacter freundii strains.

    PubMed

    Tavío Pérez, M M; Amicosante, G; Franceschini, N; Vila, J; Ruiz, J; Oratore, A; Martín-Sánchez, A M; Jiménez de Anta, M T

    1999-01-01

    The effect of fluoroquinolones in Citrobacter freundii strains that results in a decreased expression of cephalosporin-hydrolysing beta-lactamases was studied. Resistance to broad-spectrum cephalosporins and penicillins in two C. freundii clinical isolates was associated with moderate production of chromosomal AmpC-type-beta-lactamase in addition to changes in the outer membrane proteins profile with respect to wild-type C. freundii strains. Ten quinolone-resistant mutants were derived from the two clinical isolates using increasing fluoroquinolone concentrations. The level of susceptibility to cephalosporins and meropenem of these 10 mutants was increased and was associated with a 3.6-32% diminution in the hydrolyzing activity of their periplasmic extracts containing beta-lactamases on cephaloridine as compared with those from their parent strains. Susceptibility to cephalosporins and meropenem, as well as the expression of chromosomal AmpC-type-beta-lactamase in C. freundii strains, was influenced by the exposure to quinolones.

  7. Emphysematous Pyelonephritis Caused by Citrobacter freundii in a Patient with Type 2 Diabetes and Neurogenic Bladder.

    PubMed

    Kim, Min Jeong; Park, Ji Sang; Lim, Hye Jin; Jung, Jihye; Shin, Dong Geum; Lee, Ki-Deok; Jung, Yoon Young; Min, Kyung Wan; Han, Kyung-Ah

    2013-09-01

    Emphysematous pyelonephritis (EPN) is a rare, life-threatening complication of upper urinary tract infections that is characterized by the presence of gas in the renal parenchyma and perirenal space. It commonly occurs in diabetic patients. Escherichia coli are the most common causative organisms, with few reports implicating Citrobacter freundii as the etiologic agent in EPN. A 57-year-old woman with diabetes and neurogenic bladder visited at our department with confused mentality, myalgia, and general weakness. Further investigation revealed that the patient suffered from unilateral EPN with sepsis caused by C. freundii. The patient's condition was improved considerably with percutaneous drainage and use of intravenous antibiotics for several weeks. However, renal function eventually deteriorated to permanent renal failure, which required hemodialysis. In conclusion, C. freundii may be the causative pathogen of EPN in a patient with type 2 diabetes and neurogenic bladder.

  8. Biosorption of lead by citrobacter freundii immobilized on hazelnut shells

    SciTech Connect

    Bueyuekguengoer, H.; Wilk, M.; Schubert, H.

    1996-12-31

    Biosorption of lead from aqueous solutions by living and immobilized cell of C. freundii was examined as a function of metal concentration in a batch laboratory bioreactor. Lead concentrations were analyzed using Atomic Absorption Spectrophotometer (AAS). X-ray Energy Dispersion (EDX) analyses were made in order to determine the accumulation of lead on the cells and shell surfaces. Before and after the experiments the biomaterials and adsorbents were examined by Scanning Electron Microscopy (SEM). Biosorption was detected over a range of initial lead concentrations from 25{times}10{sup -3} to 200{times}10{sup -3} kg/m{sup 3}. 15 refs., 4 figs.

  9. Regulatory components in Citrobacter freundii ampC beta-lactamase induction.

    PubMed

    Lindberg, F; Westman, L; Normark, S

    1985-07-01

    Citrobacter freundii encodes an inducible chromosomal beta-lactamase similar to the constitutively expressed ampC beta-lactamase of Escherichia coli. In the latter species the ampC gene is located next to the fumarate reductase (frd) operon, whereas in C. freundii the ampC gene is known to be separated from frd by 1100 base pairs. This intervening DNA segment carries a gene, ampR, coding for a 31-kilodalton polypeptide. The cloned C. freundii OS60 ampC gene is inducible by beta-lactam antibiotics in E. coli, but only in the presence of an intact ampR gene. In the absence of inducer the AmpR protein represses C. freundii ampC synthesis 2.5-fold. Addition of beta-lactams induced expression from the cloned ampC beta-lactamase gene 11-fold. Thus, the AmpR protein has a positive effect on ampC expression in the presence of inducing beta-lactams. Two spontaneous mutants of C. freundii were isolated that constitutively overproduce the ampC beta-lactamase. The mutations in both these strains occurred outside the frd-amp region, suggesting that there is at least one additional component in the regulatory system. With the cloned C. freundii ampC gene in E. coli, mutants with the same phenotype could be obtained. These mutations were located on the E. coli chromosome. The constitutive beta-lactamase overproduction in these mutants requires the presence of an intact ampR gene.

  10. Exoelectrogenic bacterium phylogenetically related to Citrobacter freundii, isolated from anodic biofilm of a microbial fuel cell.

    PubMed

    Huang, Jianjian; Zhu, Nengwu; Cao, Yanlan; Peng, Yue; Wu, Pingxiao; Dong, Wenhao

    2015-02-01

    An electrogenic bacterium, named Citrobacter freundii Z7, was isolated from the anodic biofilm of microbial fuel cell (MFC) inoculated with aerobic sewage sludge. Cyclic voltammetry (CV) analysis exhibited that the strain Z7 had relatively high electrochemical activity. When the strain Z7 was inoculated into MFC, the maximum power density can reach 204.5 mW/m(2) using citrate as electron donor. Series of substrates including glucose, glycerol, lactose, sucrose, and rhammose could be utilized to generate power. CV tests and the addition of anode solution as well as AQDS experiments indicated that the strain Z7 might transfer electrons indirectly via secreted mediators.

  11. Cefotaxime-resistant Citrobacter freundii in isolates from blood in a tertiary teaching hospital in Northern Taiwan.

    PubMed

    Liu, Chang-Pan; Weng, Li-Chuan; Tseng, Hsiang-Kuang; Wang, Nai-Yu; Lee, Chun-Ming

    2007-10-01

    From January 2002 to December 2003, 12 patients in a tertiary teaching hospital in northern Taiwan had bloodstream infections caused by Citrobacter freundii. Seven of the 12 isolates were resistant to cefotaxime. Using polymerase chain reaction and DNA sequencing, 3 of the 7 cefotaxime-resistant C. freundii isolates were found to carry extended-spectrum beta-lactamase (ESBL). AmpC beta-lactamase genes were also detected in all strains of C. freundii. All strains of C. freundii with MICs >or=4 mg/L for cefepime were positive for ESBL. Rather than performing PCR on all cefotaxime-resistant C. freundii isolates, assessment of the MIC for cefepime might be a practical way to choose between treatment with cefepime or with carbapenems.

  12. Detection and quantification of Citrobacter freundii and C. braakii by 5'-nuclease polymerase chain reaction.

    PubMed

    Kaclíková, Eva; Krascsenicsová, Klára; Pangallo, Domenico; Kuchta, Tomás

    2005-10-01

    A new 5'-nuclease polymerase chain reaction (PCR) system for the detection and quantification of Citrobacter freundii and C. braakii was developed with primers and the probe oriented to a specific region of the cfa gene encoding a cyclopropane fatty acid synthase. The qualitative variant of the method consisted of a conventional PCR with end-point fluorimetry or agarose gel electrophoresis, and the quantitative variant used kinetic real-time PCR measurement. The PCR system was specific for C. freundii and C. braakii, detecting neither other Citrobacter spp. nor other enteric bacteria (Escherichia coli, Salmonella enterica, and others). The detection limit of the qualitative variant of the method was 10(3) cfu/mL when the amplification was followed by fluorimetry and 10(4) cfu/mL when the amplification was followed by gel electrophoresis. The real-time PCR variant of the method facilitated quantification over a range of concentrations from 10(2) to 10(8) cfu/mL, with Escherichia coli (10(6) cfu/mL) and Salmonella enterica (10(6) cfu/mL) having no effect on the quantification.

  13. Re-speciation of the original reference strains of serovars in the Citrobacter freundii (Bethesda-Ballerup group) antigenic scheme of West and edwards.

    PubMed

    Miki, K; Tamura, K; Sakazaki, R; Kosako, Y

    1996-01-01

    The antigenic scheme for the Bethesda-Ballerup group of bacteria established by West and Edwards in 1954 has continued to be applied as a serotyping scheme for Citrobacter freundii. In 1993, however, the classification of the Citrobacter was drastically revised and the species C. freundii redefined by Brenner et al. Accordingly, to judge the propriety to continuously use a single antigenic scheme for the C. freundii complex, the 90 reference strains listed in the antigenic scheme for C. freundii by West and Edwards were characterized phenotypically and specified based on the revised classification. Of these 90 strains, two strains of Hafnia alvei and one of Escherichia coli were found. Among the remaining 87 reference strains, Citrobacter youngae was the predominant species (40 strains), followed by Citrobacter braakii (25 strains), Citrobacter werkmanii (13 strains), and the unnamed Citrobacter genospecies 10 of Brenner et al (six strains). Citrobacter freundii, as redefined, accounted for only three strains and ranked behind the other four species. No overlapping with most of the 42 O-groups and 82 H-antigens was recognized between species with few exceptions. O-groups 1-9 inclusive, which were estimated to represent more than 90% of the former C.freundii strains, occurred in strains of C. youngae and C. braakii; and all nine strains of O-group 29, formerly known as the Ballerup group, were identified as C. braakii. These findings suggest that further study of the serotyping system is needed for all H2S-producing Citrobacter species.

  14. Prevalence of plasmid-mediated quinolone resistance determinants in Citrobacter freundii isolates from Anhui province, PR China.

    PubMed

    Shao, Yibo; Xiong, Zizhong; Li, Xu; Hu, Lifen; Shen, Jilu; Li, Tao; Hu, Fupin; Chen, Shudan

    2011-12-01

    This study was conducted to detect and analyse the presence of plasmid-mediated quinolone resistance (PMQR) determinants [qnr, aac(6')-Ib-cr and qepA] among Citrobacter freundii isolates from patients in Anhui province, PR China. During 2009-2010, 31 C. freundii strains were collected from various hospital units and patient specimens. Using PCR, qnr genes were detected in eight isolates, but aac(6')-Ib-cr and qepA genes were not found. The genes qnrA1, qnrB1, qnrB2, qnrB4, qnrB10 and qnrB24 were present in 6.5, 3.2, 6.5, 3.2, 3.2 and 3.2% of C. freundii isolates, respectively. A new subgene of qnrB variant (qnrB24) was found and identified for what we believe to be the first time. PFGE after XbaI digestion of genomic DNA indicated that qnr-positive strains were not clonally related. Conjugation experiments were conducted to determine whether the qnr-carrying plasmids were self-transferable, and plasmids of transconjugants were extracted and analysed. The qnr genes were transferred from three clinical isolates to their transconjugants. Two qnrA1 genes transferred quinolone resistance with a plasmid of ~11 kb, whilst the size of the plasmid carrying the qnrB4 gene was ~64 kb. The susceptibility of positive isolates and transconjugants was tested using an agar dilution method according to Clinical and Laboratory Standards Institute guidelines, and the MICs of ciprofloxacin and levofloxacin were determined using Etest strips. Most isolates with qnr genes were resistant to fluoroquinolones and other antimicrobial agents. The MICs of transconjugants showed reduced susceptibility to fluoroquinolones.

  15. Purification and characterization of an antifungal chitinase from Citrobacter freundii str. nov. haritD11.

    PubMed

    Meruvu, Haritha; Donthireddy, Sri Rami Reddy

    2014-01-01

    The purpose of the research was to study the purification and partial characterization of antifungal alkaline chitinase from a newly isolated Citrobacter freundii haritD11. The enzyme was purified in a three-step procedure involving ammonium sulfate precipitation, dialysis, and Sephadex G-100 gel filtration chromatography. The enzyme was shown to have a relative high molecular weight of 64 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis and was purified 7.3-fold with a yield of 18.8 %. It was most active at 35 °C, pH 8.0, with colloid chitin as substrate and was very stable at alkaline pH contradicting the characteristic that most of the bacterial chitinases are active at acidic pH. Further, the purified chitinase exhibited remarkable antifungal activity against pathogenic fungi Aspergillus flavus MTCC 2798 and Aspergillus niger MTCC 9652 showing diametric inhibition zones of 27 mm and 21 mm, respectively.

  16. Paraffin as oxygen vector modulates tyrosine phenol lyase production by Citrobacter freundii MTCC 2424.

    PubMed

    Azmi, Wamik; Kumar, Ajay; Dev, Varun

    2013-06-01

    The efficiency of three oxygen-vectors liquid paraffin, silicone oil and n-dodecane in the production of tyrosine phenol lyase (TPL) by Citrobacter freundii MTCC 2424 was evaluated at 4% (v/v) concentration. The liquid paraffin as oxygenvectors was found to exhibit a stimulatory effect on TPL synthesis. The liquid paraffin at 6% (v/v) resulted in 34% increase in the TPL synthesis accompanied by a 13% increase in the production of cell mass at a 10 L scale. This improvement in TPL and cell mass production in the presence of liquid paraffin can be related to the fact that liquid paraffin was capable of maintaining dissolved O2 concentration above 28% throughout the course of the fermentation. Maintenance of the dissolved O2 concentration above 28% could be viewed in terms of an adequate oxygen supply to the rapidly dividing cells of the bacterium, which in turn resulted in enhanced synthesis of TPL and cell mass.

  17. Pathway redesign for deoxyviolacein biosynthesis in Citrobacter freundii and characterization of this pigment.

    PubMed

    Jiang, Pei-xia; Wang, Hai-sheng; Xiao, Su; Fang, Ming-yue; Zhang, Rui-ping; He, Shu-ying; Lou, Kai; Xing, Xin-Hui

    2012-06-01

    Violacein (Vio) is an important purple pigment with many potential bioactivities. Deoxyviolacein, a structural analog of Vio, is always synthesized in low concentrations with Vio in wild-type bacteria. Due to deoxyviolacein's low production and difficulties in isolation and purification, little has been learned regarding its function and potential applications. This study was the first effort in developing a stable and efficient biosynthetic system for producing pure deoxyviolacein. A recombinant plasmid with vioabce genes was constructed by splicing using an overlapping extension-polymerase chain reaction, based on the Vio-synthesizing gene cluster of vioabcde, originating from Duganella sp. B2, and was introduced into Citrobacter freundii. With the viod gene disrupted in the Vio synthetic pathway, Vio production was completely abolished and the recombinant C. freundii synthesized only deoxyviolacein. Interestingly, vioe gene expression was strongly stimulated in the viod-deleted recombinant strain, indicating that viod disruptions could potentially induce polar effects upon the downstream vioe gene within this small operon. Deoxyviolacein production by this strain reached 1.9 g/L in shaker flasks. The product exhibited significant acid/alkali and UV resistance as well as significant inhibition of hepatocellular carcinoma cell proliferation at low concentrations of 0.1-1 μM. These physical characteristics and antitumor activities of deoxyviolacein contribute to illuminating its potential applications.

  18. Impact of cold plasma on Citrobacter freundii in apple juice: inactivation kinetics and mechanisms.

    PubMed

    Surowsky, Björn; Fröhling, Antje; Gottschalk, Nathalie; Schlüter, Oliver; Knorr, Dietrich

    2014-03-17

    Various studies have shown that cold plasma is capable of inactivating microorganisms located on a variety of food surfaces, food packaging materials and process equipment under atmospheric pressure conditions; however, less attention has been paid to the impact of cold plasma on microorganisms in liquid foodstuffs. The present study investigates cold plasma's ability to inactivate Citrobacter freundii in apple juice. Optical emission spectroscopy (OES) and temperature measurements were performed to characterise the plasma source. The plasma-related impact on microbial loads was evaluated by traditional plate count methods, while morphological changes were determined using scanning electron microscopy (SEM). Physiological property changes were obtained through flow cytometric measurements (membrane integrity, esterase activity and membrane potential). In addition, mathematical modelling was performed in order to achieve a reliable prediction of microbial inactivation and to establish the basis for possible industrial implementation. C. freundii loads in apple juice were reduced by about 5 log cycles after a plasma exposure of 480s using argon and 0.1% oxygen plus a subsequent storage time of 24h. The results indicate that a direct contact between bacterial cells and plasma is not necessary for achieving successful inactivation. The plasma-generated compounds in the liquid, such as H2O2 and most likely hydroperoxy radicals, are particularly responsible for microbial inactivation.

  19. Draft Genome Sequences of Citrobacter freundii Strains CF04 and A41 Isolated from Moribund, Septicemic Giant Gourami (Osphronemus goramy) in Sri Lanka.

    PubMed

    Honein, Karim; Jagoda, S S S De S; Arulkanthan, Appudurai; Ushio, Hideki; Asakawa, Shuichi

    2016-01-01

    Citrobacter freundii is a Gram-negative opportunistic pathogen associated with many infectious conditions including septicemia in humans and animals. Here, we announce the draft genome sequences of two multidrug-resistant C. freundii strains (CF04 and A41) isolated from septicemic giant gourami (Osphronemus goramy) collected from aquaria in Sri Lanka.

  20. Draft Genome Sequences of Citrobacter freundii Strains CF04 and A41 Isolated from Moribund, Septicemic Giant Gourami (Osphronemus goramy) in Sri Lanka

    PubMed Central

    Jagoda, S. S. S. De S.; Arulkanthan, Appudurai; Ushio, Hideki

    2016-01-01

    Citrobacter freundii is a Gram-negative opportunistic pathogen associated with many infectious conditions including septicemia in humans and animals. Here, we announce the draft genome sequences of two multidrug-resistant C. freundii strains (CF04 and A41) isolated from septicemic giant gourami (Osphronemus goramy) collected from aquaria in Sri Lanka. PMID:27516512

  1. Draft Genome Sequences of Citrobacter freundii Strains CF04 and A41 Isolated from Moribund, Septicemic Giant Gourami (Osphronemus goramy) in Sri Lanka.

    PubMed

    Honein, Karim; Jagoda, S S S De S; Arulkanthan, Appudurai; Ushio, Hideki; Asakawa, Shuichi

    2016-01-01

    Citrobacter freundii is a Gram-negative opportunistic pathogen associated with many infectious conditions including septicemia in humans and animals. Here, we announce the draft genome sequences of two multidrug-resistant C. freundii strains (CF04 and A41) isolated from septicemic giant gourami (Osphronemus goramy) collected from aquaria in Sri Lanka. PMID:27516512

  2. CFE-1, a novel plasmid-encoded AmpC beta-lactamase with an ampR gene originating from Citrobacter freundii.

    PubMed

    Nakano, Ryuichi; Okamoto, Ryoichi; Nakano, Yumiko; Kaneko, Kenichi; Okitsu, Naohiro; Hosaka, Yoshio; Inoue, Matsuhisa

    2004-04-01

    A clinical isolate of Escherichia coli from a patient in Japan, isolate KU6400, was found to produce a plasmid-encoded beta-lactamase that conferred resistance to extended-spectrum cephalosporins and cephamycins. Resistance arising from production of a beta-lactamase could be transferred by either conjugation or transformation with plasmid pKU601 into E. coli ML4947. The substrate and inhibition profiles of this enzyme resembled those of the AmpC beta-lactamase. The resistance gene of pKU601, which was cloned and expressed in E. coli, proved to contain an open reading frame showing 99.8% DNA sequence identity with the ampC gene of Citrobacter freundii GC3. DNA sequence analysis also identified a gene upstream of ampC whose sequence was 99.0% identical to the ampR gene from C. freundii GC3. In addition, a fumarate operon (frdABCD) and an outer membrane lipoprotein (blc) surrounding the ampR-ampC genes in C. freundii were identified, and insertion sequence (IS26) elements were observed on both sides of the sequences identified (forming an IS26 composite transposon); these results confirm the evidence of the translocation of a beta-lactamase-associated gene region from the chromosome to a plasmid. Finally, we describe a novel plasmid-encoded AmpC beta-lactamase, CFE-1, with an ampR gene derived from C. freundii.

  3. [Microbial contamination of water by pipe and tube materials. 3. Behavior of E. coli, Citrobacter freundii and Klebsiella pneumoniae].

    PubMed

    Schoenen, D; Schlömer, G

    1989-08-01

    Materials water comes into contact with can promote the microbial growth as it could be shown before. The reaction of an unspecific microorganism flora and of Legionella pneumophila in pipes and hoses has been described in the two previous communications. The investigation with L. pneumophila has shown that even a pathogen organism can grow upon the materials. Therefore it was of special interest to prove whether indicator organisms for the testing of drinking water can grow in pipes and hoses as well. Escherichia coli, Citrobacter freundii and Klebsiella pneumoniae grew after the experimental contamination for many weeks on the rubber hose until the test was finally stopped, in the other pipes and hoses (glass, high-grade steel, PVC, PE, PA, PTFE and silicone) E. coli could be found for maximal 7 weeks, Citrobacter freundii for 1 week and Klebsiella pneumoniae for maximal 3 weeks. In the copper pipe the organisms could be found only for a few days. PMID:2673263

  4. CTX-M-14 β-lactamase-producing Citrobacter freundii isolated in Venezuela.

    PubMed

    Millán, Beatriz; Ghiglione, Bárbara; Díaz, Tulia; Gutkind, Gabriel; Araque, María

    2011-01-01

    A clinical isolate of C. freundii with reduced susceptibility to extended-spectrum β-lactams from a woman with cystocele associated with recurrent urinary tract infection was analyzed. Susceptibility tests, double disk synergy tests (DDST) and enzymatic activity by the agar iodometric method suggested the presence of ESBLs. Conjugation experiments revealed the presence of a large conjugative plasmid (pLM07/20) with an exclusive FrepB replicon type (IncF/FIB). PCR analysis and sequencing confirmed the presence of the blaCTX-M-14 gene in the pLM07/20 from C. freundii.LM07/10. Although this is the first report of CTX-M-14 in Venezuela, we alert the medical community that future increase of these β-lactamases in our city could be due to dissemination of plasmids into bacterial populations.

  5. High level expression of an acid-stable phytase from Citrobacter freundii in Pichia pastoris.

    PubMed

    Zhao, Wei; Xiong, Aisheng; Fu, Xiaoyan; Gao, Feng; Tian, Yongsheng; Peng, Rihe

    2010-12-01

    To obtain a high level expression of phytase with favorable characteristics, a codon-optimized phytase gene from Citrobacter freundii was synthesized and transferred into Pichia pastoris. Small-scale expression experiments and activity assays were used to screen positive colonies. After purified by Ni²+-NTA agarose affinity column, the characterizations of the recombinant phytase were determined. The recombinant phytase (r-phyC) had two distinct pH optima at 2.5 and 4.5 and an optimal temperature at 50 °C. It retained more than 80% activity after being incubated under various buffer (pH 1.5-8.0) at 37 °C for 1 h. The specific activity, Km, and Vmax values of r-phyC for sodium phytate were 2,072 ± 18 U mg⁻¹, 0.52 ± 0.04 mM, and 2,380 ± 84 U mg⁻¹ min⁻¹, respectively. The enzyme activity was significantly improved by 1 mM of K+, Ca²+, and Mg²+. These characteristics contribute to its potential application in feed industry.

  6. Kinetic and spectral parameters of interaction of Citrobacter freundii methionine γ-lyase with amino acids.

    PubMed

    Morozova, E A; Bazhulina, N P; Anufrieva, N V; Mamaeva, D V; Tkachev, Y V; Streltsov, S A; Timofeev, V P; Faleev, N G; Demidkina, T V

    2010-10-01

    Kinetic parameters of Citrobacter freundii methionine γ-lyase were determined with substrates in γ-elimination reactions as well as the inhibition of the enzyme in the γ-elimination of L-methionine by amino acids with different structure. The data indicate an important contribution of the sulfur atom and methylene groups to the efficiency of binding of substrates and inhibitors. The rate constants of the enzyme-catalyzed exchange of C-α- and C-β-protons with deuterium were determined, as well as the kinetic isotope effect of the deuterium label in the C-α-position of inhibitors on the rate of exchange of their β-protons. Neither stereoselectivity in the β-proton exchange nor noticeable α-isotope effect on the exchange rates of β-protons was found. The ionic and tautomeric composition of the external Schiff base of methionine γ-lyase was determined. Spectral characteristics (absorption and circular dichroism spectra) of complexes with substrates and inhibitors were determined. The spectral and kinetic data indicate that deamination of aminocrotonate should be the rate-determining stage of the enzymatic reaction.

  7. Purification and characterization of selenocysteine beta-lyase from Citrobacter freundii

    SciTech Connect

    Chocat, P.; Esaki, N.; Tanizawa, K.; Nakamura, K.; Tanaka, H.; Soda, K.

    1985-08-01

    The purification and characterization of bacterial selenocysteine beta-lyase, an enzyme which specifically catalyzes the cleavage of L-selenocysteine to L-alanine and Se0, are presented. The enzyme, purified to near homogeneity from Citrobacter freundii, is monomeric with a molecular weight of ca. 64,000 and contains 1 mol of pyridoxal 5'-phosphate as a cofactor per mol of enzyme. L-Selenocysteine is the sole substrate. L-Cysteine is a competitive inhibitor of the enzyme. The enzyme also catalyzes the alpha, beta elimination of beta-chloro-L-alanine to form NH3, pyruvate, and Cl- and is irreversibly inactivated during the reaction. The physicochemical properties, e.g., amino acid composition and subunit structure, of the bacterial enzyme are fairly different from those of the pig liver enzyme. However, the catalytic properties of both enzymes, e.g., substrate specificity and inactivation by the substrate or a mechanism-based inactivator, beta-chloro-L-alanine, are very similar.

  8. Acute death associated with Citrobacter freundii infection in an African elephant (Loxodonta africana).

    PubMed

    Ortega, Joaquín; Corpa, Juan M; Orden, José A; Blanco, Jorge; Carbonell, María D; Gerique, Amalia C; Latimer, Erin; Hayward, Gary S; Roemmelt, Andreas; Kraemer, Thomas; Romey, Aurore; Kassimi, Labib B; Casares, Miguel

    2015-09-01

    A 21-year-old male African elephant (Loxodonta africana) died suddenly with no previous medical history. Grossly, there were severe multifocal epicardial and endocardial hemorrhages of the atria and ventricles, hydropericardium, multifocal pleural hemorrhages, and severe pulmonary congestion and edema. Histologically, there was fibrinoid vasculitis and thrombosis in the heart and lung and myocardial necrosis. Citrobacter freundii was isolated in abundance in pure culture from liver and heart samples. Low levels of multiples types of elephant endotheliotropic herpesvirus (EEHV-6, EEHV-2B, and EEHV-3A) were detected in spleen samples, but not in heart samples. The levels of EEHV DNA found were much lower than those usually associated with acute EEHV hemorrhagic disease, and many other genomic loci that would normally be found in such cases were evidently below the level of detection. Therefore, these findings are unlikely to indicate lethal EEHV disease. Polymerase chain reaction for encephalomyocarditis virus (EMCV) and toxicology for oleander (Nerium oleander) were negative. Stress, resulting from recent transport, and antimicrobial therapy may have contributed to the death of this animal.

  9. Engineered Citrobacter freundii methionine γ-lyase effectively produces antimicrobial thiosulfinates.

    PubMed

    Morozova, Elena A; Kulikova, Vitalia V; Rodionov, Alexei N; Revtovich, Svetlana V; Anufrieva, Natalya V; Demidkina, Tatyana V

    2016-01-01

    Antimicrobial activity of thiosulfinates in situ produced by mixtures of Citrobacter freundii methionine γ-lyase (MGL) with new substrates, l-methionine and S-(alkyl/allyl)-l-cysteine sulfoxides has been recently demonstrated (Anufrieva et al., 2015). This opens a way to the rational design of a new biotechnologically relevant antimicrobial drug producer. To increase the efficiency of the enzyme toward sulfoxides, the mutant forms of MGL, with the replacements of active site cysteine 115 with alanine (C115A MGL) and histidine (C115H MGL) were obtained. The replacement of cysteine 115 by histidine results in the loss of activity of the mutant enzyme in the γ-elimination reaction of physiological substrate, whereas the activity in the β-elimination reaction of characteristic substrates persists. However, the catalytic efficiency of C115H MGL in the β-elimination reaction of S-substituted l-cysteine sulfoxides is increased by about an order of magnitude compared to the wild type MGL. The antibacterial activity of C115H MGL mixtures with a number of sulfoxides was assessed against Gram-positive and Gram-negative bacteria. The bacteriostatic effect was more pronounced against Gram-positive than against Gram-negative bacteria, while antibacterial potential proved to be quite similar. Thus, the mutant enzyme C115H MGL is an effective catalyst, in particular, for decomposition of sulfoxides and the pharmacological couples of the mutant form with sulfoxides might be new antimicrobial agents.

  10. Resistance to oxyimino beta-lactams due to a mutation of chromosomal beta-lactamase in Citrobacter freundii.

    PubMed

    Haruta, S; Nukaga, M; Taniguchi, K; Sawai, T

    1998-01-01

    The duplicative mutation of an Ala-Val-Arg sequence at positions 208 to 210 in the loop structure of Enterobacter cloacae class C beta-lactamase caused substrate specificity extension to oxyimino beta-lactam antibiotics and this chromosomal mutation provided bacterial cells with high resistance to the beta-lactams (M. Nukaga et al, 1995, J. Biol. Chem. 270, 5729-5735). In order to confirm the universality of this phenomenon among other class C beta-lactamases, the duplicative mutation was applied to a class C beta-lactamase of Citrobacter freundii, which has 74% homology to the E. cloacae beta-lactamase amino acid sequence. The counterpart sequence to the Ala-Val-Arg of the E. cloacae enzyme in C. freundii beta-lactamase was identified to be Pro-Val-His. A Pro-Val-His sequence was inserted just after the native Pro-Val-His sequence at positions 208 to 210 in the C. freundii beta-lactamase. The resulting mutant of C. freundii beta-lactamase obtained a striking characteristic that we expected, showing substrate specificity extension to oxyimino beta-lactams. Nearly the same result was obtained with the insertion of an Ala-Val-Arg sequence after the native Pro-Val-His sequence. These results indicate that structural modification of this locus commonly induces modification of the substrate specificity to unfavorable substrates for many chromosomal class C beta-lactamases produced by gram-negative bacteria.

  11. Draft genome sequence of Citrobacter freundii strain ST2, a γ-proteobacterium that produces N-acylhomoserine lactones.

    PubMed

    Wang, Yan; Zhou, Jin

    2015-12-01

    Citrobacter freundii strain ST2, isolated from the algae bloom sample, possesses an N-acylhomoserine lactone (AHL) production activity that secretes short-chain AHL molecules. In this study, we sequenced the complete genome of C. freundii strain ST2 to understand the molecular regulation of the AHL system and to search for the AHL gene in this bacterium. The results show that the genome size is 4.89 Mb with a G + C content of 51.96%. 4626 function proteins were predicted and 3647 proteins were assigned to COG functional categories. A predicted AHL-coding gene LuxR was found at contig 4 and the length was 1541 bp. The strain temporary deposited at Shenzhen Public Platform of Screening & Application of Marine Microbial Resources (Shenzhen, China), and the genome sequence can be accessed at GenBank under the accession no. LJSQ00000000.

  12. Molecular cloning, co-expression, and characterization of glycerol dehydratase and 1,3-propanediol dehydrogenase from Citrobacter freundii.

    PubMed

    Qi, Xianghui; Deng, Wenying; Wang, Fei; Guo, Qi; Chen, Huayou; Wang, Liang; He, Xiang; Huang, Ribo

    2013-06-01

    1,3-Propanediol (1,3-PD), an important material for chemical industry, is biologically synthesized by glycerol dehydratase (GDHt) and 1,3-propanediol dehydrogenase (PDOR). In present study, the dhaBCE and dhaT genes encoding glycerol dehydratase and 1,3-propanediol dehydrogenase respectively were cloned from Citrobacter freundii and co-expressed in E. coli. Sequence analysis revealed that the cloned genes were 85 and 77 % identical to corresponding gene of C. freundii DSM 30040 (GenBank No. U09771), respectively. The over-expressed recombinant enzymes were purified by nickel-chelate chromatography combined with gel filtration, and recombinant GDHt and PDOR were characterized by activity assay, kinetic analysis, pH, and temperature optimization. This research may form a basis for the future work on biological synthesis of 1,3-PD.

  13. Complete Genome Sequence of Multidrug-Resistant Citrobacter freundii Strain P10159, Isolated from Urine Samples from a Patient with Esophageal Carcinoma.

    PubMed

    Liu, Xiaodong; Huang, Yong; Xu, Xiaomeng; Zhao, Yachao; Sun, Qiang; Zhang, Zhiyi; Zhang, Xianglilan; Wu, Yi; Wang, Jie; Zhou, Dongsheng; An, Xiaoping; Pei, Guangqian; Wang, Yunfei; Mi, Zhiqiang; Yin, Zhe; Tong, Yigang

    2016-01-01

    Citrobacter freundii is an opportunistic pathogen that can cause diarrhea, septicemia, meningitis, and urinary tract infections. We report here the complete genome sequence of C. freundii strain P10159, isolated from urine samples from a patient in China with esophageal carcinoma. The genome has 5,080,321 bp and 4,768 coding sequences, with a G+C content of 51.7%.

  14. NDM-1-Producing Citrobacter freundii, Escherichia coli, and Acinetobacter baumannii Identified from a Single Patient in China.

    PubMed

    Huang, Ying-Min; Zhong, Lan-Lan; Zhang, Xue-Fei; Hu, Hang-Tong; Li, Yu-Qi; Yang, Xiao-Rong; Feng, Lian-Qiang; Huang, Xi; Tian, Guo-Bao

    2015-08-01

    We identified New Delhi metallo-β-lactamase (NDM-1)-producing Citrobacter freundii GB032, Escherichia coli GB102, and Acinetobacter baumannii GB661 in urine and stool samples from a single patient in China. Plasmid profiling and Southern blotting indicated that blaNDM-1 from GB032 and that from GB102 were likely located on the same plasmid, while blaNDM-1 from GB661 was located on a very large (>400-kb) plasmid. This case underscores the broad host range of blaNDM-1 and its potential to spread between members of the family Enterobacteriaceae and A. baumannii.

  15. 1,3-Propanediol production by Escherichia coli using genes from Citrobacter freundii atcc 8090.

    PubMed

    Przystałowska, Hanna; Zeyland, Joanna; Kośmider, Alicja; Szalata, Marlena; Słomski, Ryszard; Lipiński, Daniel

    2015-01-01

    Compared with chemical synthesis, fermentation has the advantage of mass production at low cost, and has been used in the production of various industrial chemicals. As a valuable organic compound, 1,3-propanediol (1,3-PDO) has numerous applications in the production of polymers, lubricants, cosmetics and medicines. Here, conversion of glycerol (a renewable substrate and waste from biodiesel production) to 1,3-PDO by E. coli bacterial strain carrying altered glycerol metabolic pathway was investigated. Two gene constructs containing the 1,3-PDO operon from Citrobacter freundii (pCF1 and pCF2) were used to transform the bacteria. The pCF1 gene expression construct contained dhaBCE genes encoding the three subunits of glycerol dehydratase, dhaF encoding the large subunit of the glycerol dehydratase reactivation factor and dhaG encoding the small subunit of the glycerol dehydratase reactivating factor. The pCF2 gene expression construct contained the dhaT gene encoding the 1,3-propanediol dehydrogenase. Expression of the genes cloned in the above constructs was under regulation of the T7lac promoter. RT-PCR, SDS-PAGE analyses and functional tests confirmed that 1,3-PDO synthesis pathway genes were expressed at the RNA and protein levels, and worked flawlessly in the heterologous host. In a batch flask culture, in a short time applied just to identify the 1,3-PDO in a preliminary study, the recombinant E. coli bacteria produced 1.53 g/L of 1,3-PDO, using 21.2 g/L of glycerol in 72 h. In the Sartorius Biostat B Plus reactor, they produced 11.7 g/L of 1,3-PDO using 24.2 g/L of glycerol, attaining an efficiency of 0.58 [mol1,3-PDO/molglycerol].

  16. The role of active site tyrosine 58 in Citrobacter freundii methionine γ-lyase.

    PubMed

    Anufrieva, Natalya V; Faleev, Nicolai G; Morozova, Elena A; Bazhulina, Natalia P; Revtovich, Svetlana V; Timofeev, Vladimir P; Tkachev, Yaroslav V; Nikulin, Alexei D; Demidkina, Tatyana V

    2015-09-01

    In the spatial structure of methionine γ-lyase (MGL, EC 4.4.1.11) from Citrobacter freundii, Tyr58 is located at H-bonding distance to the oxygen atom of the phosphate "handle" of pyridoxal 5'-phosphate (PLP). It was replaced for phenylalanine by site-directed mutagenesis. The X-ray structure of the mutant enzyme was determined at 1.96Å resolution. Comparison of spatial structures and absorption spectra of wild-type and mutant holoenzymes demonstrated that the replacement did not result in essential changes of the conformation of the active site Tyr58Phe MGL. The Kd value of PLP for Tyr58Phe MGL proved to be comparable to the Kd value for the wild-type enzyme. The replacement led to a decrease of catalytic efficiencies in both γ- and β-elimination reactions of about two orders of magnitude as compared to those for the wild-type enzyme. The rates of exchange of C-α- and C-β- protons of inhibitors in D2O catalyzed by the mutant form are comparable with those for the wild-type enzyme. Spectral data on the complexes of the mutant form with the substrates and inhibitors showed that the replacement led to a change of rate the limiting step of the physiological reaction. The results allowed us to conclude that Tyr58 is involved in an optimal positioning of the active site Lys210 at some stages of γ- and β-elimination reactions. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications.

  17. Inactivation of the ampD gene causes semiconstitutive overproduction of the inducible Citrobacter freundii beta-lactamase.

    PubMed Central

    Lindberg, F; Lindquist, S; Normark, S

    1987-01-01

    In Citrobacter freundii and Enterobacter cloacae, synthesis of AmpC beta-lactamase is inducible by the addition of beta-lactams to the growth medium. Spontaneous mutants that constitutively overproduce the enzyme occur at a high frequency. When the C. freundii ampC beta-lactamase gene is cloned into Escherichia coli together with the regulatory gene ampR, beta-lactamase expression from the clone is inducible. Spontaneous cefotaxime-resistant mutants were selected from an E. coli strain carrying the cloned C. freundii ampC and ampR genes on a plasmid. Virtually all isolates had chromosomal mutations leading to semiconstitutive overproduction of beta-lactamase. The mutation ampD2 in one such mutant was caused by an IS1 insertion into the hitherto unknown ampD gene, located between nadC and aroP at minute 2.4 on the E. coli chromosome. The wild-type ampD allele cloned on a plasmid could fully trans-complement beta-lactamase-overproducing mutants of both E. coli and C. freundii, restoring the wild-type phenotype of highly inducible enzyme synthesis. This indicates that these E. coli and C. freundii mutants have their lesions in ampD. We hypothesize that induction of beta-lactamase synthesis is caused by blocking of the AmpD function by the beta-lactam inducer and that this leads directly or indirectly to an AmpR-mediated stimulation of ampC expression. PMID:3032901

  18. Characterization of chromosomal qnrB and ampC alleles in Citrobacter freundii isolates from different origins.

    PubMed

    Liao, Xiaoping; Fang, Liangxing; Li, Liang; Sun, Jian; Li, Xingping; Chen, Muya; Deng, Hui; Yang, Qiu'e; Li, Xue; Liu, Yahong

    2015-10-01

    The association of ESBLs (extended-spectrum beta-lactamases)/pAmpCs (plasmid-mediated AmpC β-lactamases) with PMQR (plasmid mediated quinolone resistance) in gram-negative bacteria has been of great concern. The present study was performed to characterize the diversity, gene location, genetic context, and evolution of ampC and qnrB alleles in isolates of Citrobacter freundii. Fifteen isolates of C. freundii were identified from a total of 788 isolates of Enterobacteriaceae derived from humans, animals, animal food products, and the environment between 2010 and 2012. Co-existence of qnrB/ΔqnrB with ampC was detected in all C. freundii isolates. Both ampC and qnrB genes were found to be located on the chromosome, but were distantly separated on the chromosome. Seven and six novel alleles were discovered for the 10 ampC and qnrB variants detected in this study, respectively. Phylogenetic analysis showed that the new alleles differed a little from the variants of ampC/qnrB previously described in this genus. The genetic context surrounding ampC genes was AmpR-AmpC-Blc-SugE. However, five different genetic contexts surrounding qnrB/ΔqnrB genes were observed, but they occurred in all cases between the pspF and sapA genes. Additionally, cloning experiments showed that the regions containing different qnrB alleles, even with different genetic contexts, contributed to the reduction of quinolone susceptibility. Our results showed that the chromosomal ampC and qnrB alleles are closely related to C. freundii. However, unlike ampC, qnrB alleles seemed to be related to the genetic contexts surrounding them. The evolution of these two genes in C. freundii isolates might be through different pathways.

  19. Molecular dynamics simulations of class C beta-lactamase from Citrobacter freundii: insights into the base catalyst for acylation.

    PubMed

    Díaz, Natalia; Suárez, Dimas; Sordo, Tomás L

    2006-01-17

    Herein, we present results from molecular dynamics (MD) simulations of the class C beta-lactamase from Citrobacter freundii and its Michaelis complex with aztreonam. Four different configurations of the active site were modeled in aqueous solution, and their relative stability was estimated by means of quantum mechanical energy calculations. For the free enzyme, the energetically most stable configurations present a neutral Lys67 residue or an anionic Tyr150 side chain. Our calculations predict that these two configurations are quite close in terms of free energy, the anionic Tyr150 state being favored by approximately 1 kcal/mol. In contrast, for the noncovalent complex formed between the C. freundii enzyme and aztreonam, the energetic analyses predict that the configuration with the neutral Lys67 residue is much more stable than the anionic Tyr150 one (approximately 20 kcal/mol). Moreover, the MD simulations reveal that the neutral Lys67 state results in a proper enzyme-aztreonam orientation for nucleophilic attack and in a very stable contact between the nucleophilic hydroxyl group of Ser64 and the neutral amino side chain of Lys67. Thus, both the computed free energies and the structural analyses support the assignation of Lys67 as the base catalyst for the acylation step in the native form of the C. freundii enzyme.

  20. Conversion of glycerol to 1,3-propanediol by Citrobacter freundii and Hafnia alvei - newly isolated strains from the Enterobacteriaceae.

    PubMed

    Drożdżyńska, Agnieszka; Pawlicka, Joanna; Kubiak, Piotr; Kośmider, Alicja; Pranke, Dorota; Olejnik-Schmidt, Agnieszka; Czaczyk, Katarzyna

    2014-09-25

    In this study, nearly 4000 bacterial strains from the family of Enterobacteriaceae isolated from different environments were screened for ability to convert glycerol to 1,3-propanediol (1,3-PD). The aim of the research was to isolate 1,3-PD producers from the natural environment, identify and characterize the best isolates. Three selective media were tested to usefulness in the isolation of bacteria from the family Enterobacteriaceae. Only, 28% of examined isolates could synthesize 1,3-PD from glycerol. 1,3-PD producing bacteria were identified by API 20E tests and 16S rRNA sequences to be Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter freundii and Hafnia alvei. It is the first time, when the fermentation glycerol to 1,3-PD by H. alvei was investigated. The selected strains (C. freundii AD119 and H. alvei AD27) were analyzed on a bioreactor scale under constant pH value 7.0 at temperature of 30°C and 37°C. After 40h in batch fermentation, H. alvei AD27 produced 11.3g/L of 1,3-PD at 37°C. For C. freundii AD119, the best results were obtained at temperature of 30°C. After 24h of fermentation, the 1,3-PD concentration reached above 23 g/L of 1,3-PD. PMID:24768868

  1. Conversion of glycerol to 1,3-propanediol by Citrobacter freundii and Hafnia alvei - newly isolated strains from the Enterobacteriaceae.

    PubMed

    Drożdżyńska, Agnieszka; Pawlicka, Joanna; Kubiak, Piotr; Kośmider, Alicja; Pranke, Dorota; Olejnik-Schmidt, Agnieszka; Czaczyk, Katarzyna

    2014-09-25

    In this study, nearly 4000 bacterial strains from the family of Enterobacteriaceae isolated from different environments were screened for ability to convert glycerol to 1,3-propanediol (1,3-PD). The aim of the research was to isolate 1,3-PD producers from the natural environment, identify and characterize the best isolates. Three selective media were tested to usefulness in the isolation of bacteria from the family Enterobacteriaceae. Only, 28% of examined isolates could synthesize 1,3-PD from glycerol. 1,3-PD producing bacteria were identified by API 20E tests and 16S rRNA sequences to be Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter freundii and Hafnia alvei. It is the first time, when the fermentation glycerol to 1,3-PD by H. alvei was investigated. The selected strains (C. freundii AD119 and H. alvei AD27) were analyzed on a bioreactor scale under constant pH value 7.0 at temperature of 30°C and 37°C. After 40h in batch fermentation, H. alvei AD27 produced 11.3g/L of 1,3-PD at 37°C. For C. freundii AD119, the best results were obtained at temperature of 30°C. After 24h of fermentation, the 1,3-PD concentration reached above 23 g/L of 1,3-PD.

  2. L-methionine gamma-lyase from Citrobacter freundii: cloning of the gene and kinetic parameters of the enzyme.

    PubMed

    Manukhov, I V; Mamaeva, D V; Morozova, E A; Rastorguev, S M; Faleev, N G; Demidkina, T V; Zavilgelsky, G B

    2006-04-01

    It is shown for the first time for the Enterobacteriaceae family that a gene encoding L-methionine gamma-lyase (MGL) is present in the genome of Citrobacter freundii. Homogeneous enzyme has been purified from C. freundii cells and its N-terminal sequence has been determined. The hybrid plasmid pUCmgl obtained from the C. freundii genomic library contains an EcoRI insert of about 3000 bp, which ensures the appearance of MGL activity when expressed in Escherichia coli TG1 cells. The nucleotide sequence of the EcoRI fragment contains two open reading frames. The first frame (the megL gene) encodes a protein of 398 amino acid residues that has sequence homology with MGLs from different sources. The second frame encodes a protein with sequence homology with proteins belonging to the family of permeases. To overexpress the megL gene it was cloned into pET-15b vector. Recombinant enzyme has been purified and its kinetic parameters have been determined. It is demonstrated that a presence of a hybrid plasmid pUCmgl, containing the megL gene in the E. coli K12 cells, leads to a decrease in efficiency of EcoKI-restriction. It seems likely that decomposition of L-methionine under the action of MGL leads to a decrease in the intracellular content of S-adenosylmethionine. Expression of the megL gene in the C. freundii genome occurs only upon induction by a significant amount of L-methionine.

  3. Shiga-like toxin II-related cytotoxins in Citrobacter freundii strains from humans and beef samples.

    PubMed

    Schmidt, H; Montag, M; Bockemühl, J; Heesemann, J; Karch, H

    1993-02-01

    By hybridizing colonies grown from 928 individual stool samples of patients suffering from diarrhea with oligonucleotide probes 772 and 849 complementary to Shiga-like toxin I (SLT-I) and SLT-II gene sequences, respectively, we identified two strains that hybridized with probe 849, which biochemical identification revealed as Citrobacter freundii. An additional five slt-II probe-positive isolates were screened from 81 beef samples. Polymerase chain reaction analysis and restriction of amplified products provided evidence for slt-II-related genes in all seven strains. From C. freundii LM 76, the genes encoding the A and B subunits were cloned in pUC 18 vectors and sequenced. The gene encoding the A subunit differed from that of Escherichia coli slt-IIvhc in 4 bases, resulting in two amino acid residue differences. In 11, 13, and 11 nucleotides, differentiation of slt-IIA, slt-IIcA, and vtx2haA, respectively, was found. These differences affected the predicted amino acid sequence as follows: there were six amino acid differences with SLT-IIA, five with SLT-IIcA, and four with VTx2haA. The nucleotide sequence of the gene encoding the B subunit is identical to slt-IIvhcB and differed from slt-IIcB and vtx2haB by only a single nucleotide base, but this resulted in a predicted amino acid sequence identical to that reported for these toxins. We therefore termed the toxin genes C. freundii slt-IIcA and slt-IIcB. Culture filtrates inoculated with material from the colonies from primary cultures were cytotoxic to Vero cells. Neutralization assays with antisera to E. coli SLT-I, SLT-II, and SLT-IIvhc revealed that antibodies against SLT-IIvhc reduced the C. freundii cytotoxic activity specifically and to the same degree as with the E. coli SLT-IIvhc control strain. In five of the seven strains tested, subcultivation on both a liquid or solid medium resulted in loss of cytotoxic activity. With polymerase chain reaction, we demonstrated that loss of cytotoxic activity ran

  4. Carbohydrate binding specificities and crystal structure of the cholera toxin-like B-subunit from Citrobacter freundii.

    PubMed

    Jansson, Lena; Angström, Jonas; Lebens, Michael; Imberty, Anne; Varrot, Annabelle; Teneberg, Susann

    2010-05-01

    Enterotoxigenic Escherichia coli and Vibrio cholerae are well known causative agents of severe diarrheal diseases. Both pathogens produce AB(5) toxins, with one enzymatically active A-subunit and a pentamer of receptor-binding B-subunits. The primary receptor for both B-subunits is the GM1 ganglioside (Galbeta3GalNAcbeta4(NeuAcalpha3)Galbeta4GlcbetaCer), but the B-subunits from porcine isolates of E. coli also bind neolacto-(Galbeta4GlcNAcbeta-)terminated glycoconjugates and the B-subunits from human isolates of E. coli (hLTB) have affinity for blood group A type 2-(GalNAcalpha3(Fucalpha2)Galbeta4GlcNAcbeta-)terminated glycoconjugates. A B-subunit with 73% sequence identity to the B-subunits of cholera toxin and the heat-labile toxin of E. coli is produced by certain strains of enteropathogenic E. coli and by Citrobacter freundii. This C. freundii B-subunit (CFXB) has now been expressed in V. cholerae, and isolated in high yields. Glycosphingolipid binding studies show that CFXB binds to the GM1 ganglioside with high affinity. In addition, CFXB has high affinity for both neolacto-terminated and blood group A type 2-terminated glycoconjugates. The crystal structure of the pentameric arrangement of C. freundii B-subunits display high structural similarity with related proteins from E. coli and V. cholerae and oligosaccharide binding sites can be identified on the protein surface. Small changes in the 88-95 loop connecting the GM1 and blood group A binding sites explains the minor changes in affinity seen for these two ligands. However, the enhanced affinity of CFXB for neolacto-terminated structures can be sought in the Lys34Tyr substitution affording additional hydrogen bond interactions between the tyrosyl side chain and the GlcNAcbeta3Galb4Glcbeta1 segment of neolactotetraosylceramide via bridging water molecules.

  5. Diarrhea-associated biofilm formed by enteroaggregative Escherichia coli and aggregative Citrobacter freundii: a consortium mediated by putative F pili

    PubMed Central

    2010-01-01

    Background Enteroaggregative Escherichia coli (EAEC) are enteropathogenic strains identified by the aggregative adhesion (AA) pattern that share the capability to form biofilms. Citrobacter freundii is classically considered as an indigenous intestinal species that is sporadically associated with diarrhea. Results During an epidemiologic study focusing on infantile diarrhea, aggregative C. freundii (EACF) and EAEC strains were concomitantly recovered from a severe case of mucous diarrhea. Thereby, the occurrence of synergic events involving these strains was investigated. Coinfection of HeLa cells with EACF and EAEC strains showed an 8-fold increase in the overall bacterial adhesion compared with single infections (P < 0.001). The synergic effect was mediated by physical interactions among the bacteria and primed in the absence of chemical signaling and without the participation of host cells. Thus, significant increases (2.7-fold on average) in bacterial adhesion were also observed during the formation of mixed biofilms on abiotic surfaces. Bacterial settling assays showed that EAEC strains harboring F-pili genes (traA) were capable of forming bacterial aggregates only in the presence of EACF. Scanning electronic microscopy analyses revealed that bacterial aggregates as well as enhanced biofilms formed by EACF and traA-positive EAEC were mediated by non-bundle forming, flexible pili. Moreover, mixed biofilms formed by EACF and traA-positive EAEC strains were significantly reduced using nonlethal concentration of zinc, a specific inhibitor of F pili. In addition, EAEC strains isolated from diarrheic children frequently produced single biofilms sensitive to zinc. Conclusions Putative F pili expressed by EAEC strains boosted mixed biofilm formation when in the presence of aggregative C. freundii. PMID:20175929

  6. Comparison of the taxonomy, serology, drug resistance transfer, and virulence of Citrobacter freundii strains from mammals and poikilothermic hosts.

    PubMed Central

    Toranzo, A E; Cutrín, J M; Roberson, B S; Núñez, S; Abell, J M; Hetrick, F M; Baya, A M

    1994-01-01

    In this study, the phenotypic, antigenic, and virulence characteristics of 32 Citrobacter freundii strains of fish, human, and veterinary origin were comparatively analyzed. In addition, the spread of drug resistance factors by conjugation was investigated. Regardless of the source of isolation, the strains exhibited variable reactions mainly for arginine dihydrolase, ornithine decarboxylase, and fermentation of sucrose, melibiose, amygdalin, and salicin. Total fatty acid methyl ester analysis by gas chromatography proved to be useful for an intratypic differentiation within the C. freundii strains studied. In fact, although all of the isolates exhibited similar fatty acid methyl ester profiles, significant differences in the major fatty acids 16:1 and 16:0 and in the 17:0 delta region were observed between the isolates from salmonids and the remaining strains. Serological studies using agglutination tests, analysis of lipopolysaccharides (LPS), and the corresponding immunoblots with 13 antisera indicated a great antigenic diversity among the strains. Common LPS patterns were shared only by some isolates showing high cross-agglutination titers. In contrast, although all strains exhibited very similar surface protein patterns, only two common outer membrane proteins of 54 and 58 kDa were immunologically related. Infectivity trials performed in mice and rainbow trout indicated that all of the C. freundii strains were not pathogenic for mice (50% lethal dose of > 5 x 10(7)). Although the isolates displayed a low degree of virulence for trout, inoculated strains were always recovered from the survivors in pure culture.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8031079

  7. Alliin is a suicide substrate of Citrobacter freundii methionine γ-lyase: structural bases of inactivation of the enzyme.

    PubMed

    Morozova, Elena A; Revtovich, Svetlana V; Anufrieva, Natalya V; Kulikova, Vitalia V; Nikulin, Alexey D; Demidkina, Tatyana V

    2014-11-01

    The interaction of Citrobacter freundii methionine γ-lyase (MGL) and the mutant form in which Cys115 is replaced by Ala (MGL C115A) with the nonprotein amino acid (2R)-2-amino-3-[(S)-prop-2-enylsulfinyl]propanoic acid (alliin) was investigated. It was found that MGL catalyzes the β-elimination reaction of alliin to form 2-propenethiosulfinate (allicin), pyruvate and ammonia. The β-elimination reaction of alliin is followed by the inactivation and modification of SH groups of the wild-type and mutant enzymes. Three-dimensional structures of inactivated wild-type MGL (iMGL wild type) and a C115A mutant form (iMGL C115A) were determined at 1.85 and 1.45 Å resolution and allowed the identification of the SH groups that were oxidized by allicin. On this basis, the mechanism of the inactivation of MGL by alliin, a new suicide substrate of MGL, is proposed. PMID:25372692

  8. Citrobacter freundii carrying blaKPC-2 and blaNDM-1: characterization by whole genome sequencing

    PubMed Central

    Wu, Wenjing; Espedido, Björn; Feng, Yu; Zong, Zhiyong

    2016-01-01

    A carbapenem-resistant Citrobacter freundii strain WCHCF65 was recovered from hospital sewage and was characterized by genome sequencing and conjugation experiments. The strain carried nine genes encoding β-lactamases including two carbapenemase genes, blaNDM-1 and blaKPC-2. blaNDM-1 was carried on an IncX3 plasmid, which was identical to a plasmid found in a local Escherichia coli, suggesting interspecies horizontal transfer. blaKPC-2 was bracketed by two copies of insertion sequence ISKpn19, which could form a composite transposon with the potential to mobilize blaKPC-2, on a new type of plasmid. The coexistence of blaNDM-1 and blaKPC-2 conferred higher levels of resistance to carbapenems compared with blaNDM-1 or blaKPC-2 alone. The coexistence of these carbapenemase genes, on two different plasmids, in one strain may allow new genetic platforms to be generated to mediate their spread. PMID:27465241

  9. Alliin is a suicide substrate of Citrobacter freundii methionine γ-lyase: structural bases of inactivation of the enzyme.

    PubMed

    Morozova, Elena A; Revtovich, Svetlana V; Anufrieva, Natalya V; Kulikova, Vitalia V; Nikulin, Alexey D; Demidkina, Tatyana V

    2014-11-01

    The interaction of Citrobacter freundii methionine γ-lyase (MGL) and the mutant form in which Cys115 is replaced by Ala (MGL C115A) with the nonprotein amino acid (2R)-2-amino-3-[(S)-prop-2-enylsulfinyl]propanoic acid (alliin) was investigated. It was found that MGL catalyzes the β-elimination reaction of alliin to form 2-propenethiosulfinate (allicin), pyruvate and ammonia. The β-elimination reaction of alliin is followed by the inactivation and modification of SH groups of the wild-type and mutant enzymes. Three-dimensional structures of inactivated wild-type MGL (iMGL wild type) and a C115A mutant form (iMGL C115A) were determined at 1.85 and 1.45 Å resolution and allowed the identification of the SH groups that were oxidized by allicin. On this basis, the mechanism of the inactivation of MGL by alliin, a new suicide substrate of MGL, is proposed.

  10. Verotoxinogenic Citrobacter freundii associated with severe gastroenteritis and cases of haemolytic uraemic syndrome in a nursery school: green butter as the infection source.

    PubMed Central

    Tschape, H.; Prager, R.; Streckel, W.; Fruth, A.; Tietze, E.; Böhme, G.

    1995-01-01

    A summer outbreak of severe gastroenteritis followed by haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura in a nursery school and kindergarten is described. Sandwiches prepared with green butter made with contaminated parsley were the likely vehicle of infection. The parsley originated from an organic garden in which manure of pig origin was used instead of artificial fertilizers. Clonally identical verotoxinogenic Citrobacter freundii were found as causative agents of HUS and gastroenteritis and were also detected on the parsley. Images Fig. 1 Fig. 2 PMID:7781732

  11. Characterization of KPC-2-producing Escherichia coli, Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, and Klebsiella oxytoca isolates from a Chinese Hospital.

    PubMed

    Luo, Yanping; Yang, Jiyong; Ye, Liyan; Guo, Lin; Zhao, Qiang; Chen, Rong; Chen, Yong; Han, Xuelin; Zhao, Jingya; Tian, Shuguang; Han, Li

    2014-08-01

    Twelve nonduplicated KPC-2-producing enterobacterial isolates, including three Escherichia coli, two Citrobacter freundii, two Enterobacter cloacae, four Enterobacter aerogenes, and one Klebsiella oxytoca, were collected from various clinical samples within 18 months (March 2011 to September 2012). Two of the 12 patients died from infections caused by KPC-2-producing pathogens, while the rest of the patients with KPC-2-producing pathogens improved or were cured. The majority of the clinical isolates exhibited a high-level of resistance to oxyimino-cephalosporins and carbapenems, and possessed self-transferable bla(KPC-2)-carrying plasmids with sizes ranging from 20 to 120 kb. Most isolates carried bla(CTX-M) and plasmid-mediated quinolone resistance genes, while some isolates produced 16S rRNA methylases (ArmA or RmtB). The genetic environment of bla(KPC-2) of most clinical strains was consistent with the genetic structure surrounding bla(KPC-2) on the plasmid pKP048, which contains an integration structure of a Tn3-based transposon and partial Tn4401 segment. Inserted fragments (truncated bla(TEM)) were detected upstream of the bla(KPC-2) gene for two E. aerogenes strains. In conclusion, the enterobacterial isolates exhibited sporadic emergence and did not arise by clonal spread at our hospital. The outcome of infections caused by KPC-producing enterobacterial isolates and their mortality were closely associated with the baseline condition of patients. The spread of bla(KPC-2) gene between different enterobacterial species in China was mainly mediated by horizontal transfer of the Tn3-based transposons and not the bla(KPC-2)-carrying plasmids.

  12. A Salmonella fim homologue in Citrobacter freundii mediates invasion in vitro and crossing of the blood-brain barrier in the rat pup model.

    PubMed

    Hess, Petra; Altenhöfer, Artur; Khan, A Salam; Daryab, Neda; Kim, Kwang Sik; Hacker, Jörg; Oelschlaeger, Tobias A

    2004-09-01

    From the invasive Citrobacter freundii strain 3009, an invasion determinant was cloned, sequenced, and expressed. Sequence analysis of the determinant showed high homology with the fim determinant from Salmonella enterica serovar Typhimurium. The genes of the invasion determinant directed invasion of recombinant Escherichia coli K-12 strains into human epithelial cell lines of the bladder and gut as well as mannose-sensitive yeast agglutination and were termed fim(Cf) genes. Expression of the Fim(Cf) proteins was shown by (35)S labeling and/or Western blotting. In the infant rat model of experimental hematogenous meningitis, C. freundii strain 3009 and the in vitro invasive recombinant E. coli K-12 strain harboring the fim(Cf) determinant reached the cerebrospinal fluid, in contrast to the case for the control strain. The fim determinant was also necessary for efficient in vitro invasion by C. freundii, because a deletion mutant was strongly reduced in its invasion efficiency. The mutation could be complemented in trans by the corresponding genes. Invasion by C. freundii could be blocked only by d-mannose, GlcNAc, and chitin hydrolysate and not by other carbohydrates tested. In contrast, yeast agglutination was not affected by GlcNAc or chitin hydrolysate. This finding indicated mannose residues to be essential for both yeast agglutination and invasion, whereas GlcNAc (oligomer) residues of host cells are involved exclusively in invasion. These results showed the fim determinant of C. freundii to be responsible for d-mannose- and GlcNAc-dependent in vitro invasion without being assembled into pili and for crossing of the blood-brain barrier in the infant rat model.

  13. Enhanced 1,3-propanediol production by a newly isolated Citrobacter freundii strain cultivated on biodiesel-derived waste glycerol through sterile and non-sterile bioprocesses.

    PubMed

    Metsoviti, Maria; Zeng, An-Ping; Koutinas, Apostolis A; Papanikolaou, Seraphim

    2013-02-20

    The production of 1,3-propanediol (PD) by a newly isolated Citrobacter freundii strain [FMCC-B 294 (VK-19)] was investigated. Different grades of biodiesel-derived glycerol were employed. Slightly lower PD biosynthesis was observed in batch experiments only when crude glycerol from waste-cooking oil trans-esterification was utilized and only at elevated initial substrate concentrations employed. Batch bioreactor cultures revealed the capability of the strain to tolerate elevated amounts of substrate (glycerol up to 170 g/L) and produce quantities of PD in such high substrate concentrations. Nevertheless, maximum PD quantities (45.9 g/L) were achieved at lower initial glycerol concentrations (∼100 g/L) employed, suggesting some inhibition exerted due to the increased initial substrate concentrations. In order to improve PD production, a fed-batch fermentation was carried out and 68.1g/L of PD were produced (the highest PD quantity achieved by C. freundii strains so far) with yield per glycerol consumed ∼0.40 g/g and volumetric productivity 0.79 g/L/h. Aiming to perform a more economical and eco-friendlier procedure, batch and fed-batch fermentations under completely non-sterile conditions were carried out. During non-sterilized fed-batch process, 176 g/L of raw glycerol were converted to 66.3g/L of PD, suggesting the potentiality of the non-sterile fermentation by C. freundii FMCC-B 294.

  14. In vitro inhibition of Citrobacter freundii, a red-leg syndrome associated pathogen in raniculture, by indigenous Lactococcus lactis CRL 1584.

    PubMed

    Pasteris, Sergio E; Guidoli, Marcos G; Otero, María C; Bühler, Marta I; Nader-Macías, María E

    2011-08-01

    Red-leg syndrome (RLS) is one of the main infectious diseases that cause economic losses in Lithobates catesbeianus hatcheries, Citrobacter freundii being an etiological agent. Treatment or prevention with therapeutics or chemicals results in modifications of the indigenous microbiota, development of antibiotic resistance, presence of their residues in food and enhancement of production costs. Thus, probiotics could be used as an alternative therapy. Lactic acid bacteria are part of the indigenous microbiota of healthy frogs and can prevent pathogen colonization by different mechanisms, including the production of antagonistic substances. In this work, the evaluation and characterization of the inhibition of C. freundii CFb by Lactococcus lactis subsp. lactis CRL 1584, a potentially probiotic candidate, were carried out. This strain produced lactic acid, H(2)O(2) and bacteriocin in static and shaken conditions and inhibited pathogen growth in associative cultures, with an earlier inhibition under agitated conditions. The elimination of each of the antimicrobial metabolites partially abolished the inhibition of the pathogen, suggesting that the inhibitory effect could be attributed to a combined action of the three antagonistic molecules. Electron microphotographs revealed the damage caused by L. lactis CRL 1584 supernatants to C. freundii cells. The addition of pure lactic acid, H(2)O(2) and bacteriocin to the culture media showed that each metabolite caused different morphological modifications in C. freundii, in agreement with the effect on viable cell counts. The results support the possibility that L. lactis CRL 1584 might be considered as a probiotic to be used in the prevention of RLS in raniculture.

  15. Evaluation of the immunogenicity and biological activity of the Citrobacter freundii Vi-CRM197 conjugate as a vaccine for Salmonella enterica serovar Typhi.

    PubMed

    Rondini, Simona; Micoli, Francesca; Lanzilao, Luisa; Hale, Christine; Saul, Allan J; Martin, Laura B

    2011-03-01

    Typhoid fever remains a major health problem in developing countries. Young children are at high risk, and a vaccine effective for this age group is urgently needed. Purified capsular polysaccharide from Salmonella enterica serovar Typhi (Vi) is licensed as a vaccine, providing 50 to 70% protection in individuals older than 5 years. However, this vaccine is ineffective in infants. Vi conjugated to a carrier protein (i.e., an exoprotein A mutant from Pseudomonas aeruginosa [rEPA]) is highly immunogenic, provides long-term protection, and shows more than 90% protective efficacy in children 2 to 5 years old. Here, we describe an alternative glycoconjugate vaccine for S. Typhi, Vi-CRM(197), where Vi was obtained from Citrobacter freundii WR7011 and CRM(197), the mutant diphtheria toxin protein, was used as the carrier. We investigated the optimization of growth conditions for Vi production from C. freundii WR7011 and the immunogenicity of Vi-CRM(197) conjugates in mice. The optimal saccharide/protein ratio of the glycoconjugates was identified for the best antibody production. We also demonstrated the ability of this new vaccine to protect mice against challenge with Vi-positive Salmonella enterica serovar Typhimurium.

  16. A comparative study of solvent-assisted pretreatment of biodiesel derived crude glycerol on growth and 1,3-propanediol production from Citrobacter freundii.

    PubMed

    Anand, Pinki; Saxena, Rajendra Kumar

    2012-01-15

    The rapidly growing biodiesel industry has created a scenario, where it is both important and challenging to deal with the enormous amount of crude glycerol generated as an inherent by-product. With every 100 gallons of biodiesel produced, 5-10 gallons of the crude glycerol is left behind containing several impurities which makes its disposal difficult. The objective of the present investigation was to evaluate the impact of biodiesel-derived crude glycerol upon microbial growth and production of 1,3-propanediol by Citrobacter freundii. Five different grades of crude glycerol (obtained from biodiesel preparation using jatropha, soybean, sunflower, rice bran and linseed oils) were used. Crude glycerol caused significant inhibition of microbial growth and subsequently 1,3-propanediol production as compared to pure glycerol. Therefore, a process was developed for the treatment of crude glycerol using solvents before fermentation wherein four different non-polar solvents were examined yielding different grades of pretreated glycerol. Subsequently, the potential toxic effects of pretreated glycerol on the growth and 1,3-propanediol production by C. freundii was evaluated. In case of petroleum ether-treated crude glycerol obtained from jatropha & linseed and hexane-treated crude glycerol obtained from rice bran, the yields obtained were comparable to the pure glycerol. Similarly, soybean-derived glycerol gave comparable results after treatment with either hexane or petroleum ether.

  17. Novel genetic environment of the plasmid-mediated KPC-3 gene detected in Escherichia coli and Citrobacter freundii isolates from China.

    PubMed

    Li, G; Wei, Q; Wang, Y; Du, X; Zhao, Y; Jiang, X

    2011-04-01

    The imipenem and meropenem-resistant strains Citrobacter freundii HS70 and Escherichia coli HS510 were isolated from patients in Shanghai, China. By isoelectric focusing, PCR amplification and sequencing, these strains were each found to produce four β-lactamases: TEM-1, KPC-3, SHV-7 and CTX-M-14. A conjugation experiment and plasmid restriction digestion revealed that the bla (KPC-3) gene was located on the same plasmid in both isolates. Bidirectional primer walking sequencing showed that the nucleotide sequence surrounding the 3.8 kb bla(KPC-3) contained a 671-bp insertion similar to that previously characterized in China. The insertion was located between the promoter and the coding region of the bla(KPC-3) gene. Susceptibility testing performed on recombinant strains carrying the bla(KPC-3) gene with or without the insertion revealed that minimum inhibitory concentrations of imipenem, meropenem, cefepime, and cefotaxime for E. coli EMU-KPC3 (without insertion) were four times higher than that of E. coli EKPC3 (with insertion). The 671 bp insertion reduced bla(KPC-3) expression significantly. Taken together, these results suggest that KPC-3-producing C. freundii and E. coli have begun to emerge in our hospital.

  18. Molecular epidemiological survey of Citrobacter freundii misidentified as Cronobacter spp. (Enterobacter sakazakii) and Enterobacter hormaechei isolated from powdered infant milk formula.

    PubMed

    Giammanco, Giovanni M; Aleo, Aurora; Guida, Ivana; Mammina, Caterina

    2011-04-01

    A total of 75 powdered infant milk formula (PIF) samples collected from pharmacies and drugstores in Western Sicily, Italy, and representative of 12 different brands were analyzed in this study to evaluate their microbiological quality. According to the U.S. Food and Drug Administration protocol, 32 samples out of 75 were contaminated by enterobacteria. Commercial biochemical API(r) 20E-system identification method indicated that six PIF samples were presumptively contaminated by Cronobacter spp., but further characterization by alpha-glucosidase based polymerase chain reaction (PCR) assay identification strongly suggested that these strains did not belong to the genus Cronobacter. Phylogenetic analysis of partial 16S rRNA (rrs) sequences combined with the results of biochemical tests allowed to identify the six strains as Citrobacter freundii. Similarly, rrs sequence analysis identified as Enterobacter hormaechei 23 strains originally ascribed to Enterobacter cloacae by the API 20E system. Characterization of C. freundii and E. hormaechei PIF isolates by the DiversiLab(r) repetitive sequence-based PCR (rep-PCR) typing method revealed a variety of amplification patterns, but the recovery of the same rep-PCR genotype in several products might indicate a special adaptation of genetic clones to this food or cross-contamination through common ingredients. Antibiotic-resistance profiles were also determined, but none of the strains tested was resistant to third-generation cephalosporins or fluoroquinolones and extended-spectrum beta-lactamase activity was not detected. Our results confirm that E. hormaechei contamination of PIF is widespread, thus making it a cause for concern. Similarly to what was demonstrated for E. hormaechei, we suggest that C. freundii also may be an under-reported cause of bacterial infection, especially in high-risk neonates, due to misidentification.

  19. Four variants of the Citrobacter freundii AmpC-Type cephalosporinases, including novel enzymes CMY-14 and CMY-15, in a Proteus mirabilis clone widespread in Poland.

    PubMed

    Literacka, Elzbieta; Empel, Joanna; Baraniak, Anna; Sadowy, Ewa; Hryniewicz, Waleria; Gniadkowski, Marek

    2004-11-01

    Twenty-nine Proteus mirabilis isolates from 17 Polish hospitals were analyzed. The isolates were resistant to a variety of antimicrobials, and their patterns of resistance to beta-lactams resembled those of the constitutive class C cephalosporinase (AmpC) producers. Indeed, beta-lactamases with a pI of approximately 9.0 were found in all of the isolates, and they were subsequently identified as four AmpC-type cephalosporinases, CMY-4, -12, -14, and -15, of which the two last ones were novel enzyme variants. The enzymes were of Citrobacter freundii origin and were closely related to each other, with CMY-4 likely being the evolutionary precursor of the remaining ones. The bla(CMY) genes were located exclusively in chromosomal DNA, within EcoRI restriction fragments of the same size of approximately 10 kb. In the CMY-12- and -15-producing isolates, an additional fragment of approximately 4.5 kb hybridized with the bla(CMY) probe as well, which could have arisen from a duplication event during the evolution of the genes. In all of the isolates, the ISEcp1 mobile element, which most probably is involved in mobilization of the C. freundii ampC gene, was placed at the same distance from the 5' ends of the bla(CMY) genes, and sequences located between them were identical in isolates carrying each of the four genes. These data suggested that a single chromosome-to-chromosome transfer of the ampC gene from C. freundii to P. mirabilis could have initiated the spread and evolution of the AmpC-producing P. mirabilis in Poland. The hypothesis seems to be confirmed by pulsed-field gel electrophoresis typing, which revealed several cases of close relatedness between the P. mirabilis isolates from distant centers and showed an overall similarity between the majority of the multiresistant isolates.

  20. An Analysis of the Effects of Vancomycin and/or Vancomycin-Resistant Citrobacter freundii Exposure on the Microbial Community Structure in Soil.

    PubMed

    Cycoń, Mariusz; Borymski, Sławomir; Orlewska, Kamila; Wąsik, Tomasz J; Piotrowska-Seget, Zofia

    2016-01-01

    The occurrence of antibiotics and antibiotic resistance genes in the environment has become a subject of growing concern. The extensive use of vancomycin and other pharmaceuticals may alter the biodiversity of soil microbial communities and select antibiotic-resistant bacteria. Therefore, the purpose of the study was to evaluate the impact of vancomycin and/or vancomycin-resistant Citrobacter freundii on soil microbial communities using the denaturing gradient gel electrophoresis (DGGE) and the phospholipid fatty acid (PLFA) approaches. The experiment had a completely randomized block design with the following treatments: control soil (C), soil with vancomycin (1 mg/kg soil-VA1), soil with vancomycin (10 mg/kg soil-VA10), soil with C. freundii (Cit), soil with vancomycin (1 mg/kg soil) and C. freundii (VA1+Cit), and soil with vancomycin (10 mg/kg soil) and C. freundii (VA10+Cit). A bacterial strain resistant to vancomycin was isolated from raw sewage collected from the municipal sewage treatment plant. The obtained results indicated that the antibiotic and/or the bacterial strain exerted a selective pressure that resulted in qualitative and quantitative changes in the population of soil microorganisms. However, a multivariate analysis showed that the genetic and structural diversity of the soil microbial community was primarily affected by the incubation time and to a lesser extent by the antibiotic and introduced bacteria. DGGE analysis clearly showed that certain species within the bacterial community were sensitive to vancomycin as was evidenced by a decrease in the values of S (richness) and H (Shannon-Wiener) indices. Moreover, a PLFA method-based analysis revealed alterations in the structure of the soil microbial community as indicated by changes in the biomass of the PLFA biomarkers specific for Gram-positive and Gram-negative bacteria as well as fungi. The changes observed in the community of soil microorganisms may decrease the rate of microbial

  1. An Analysis of the Effects of Vancomycin and/or Vancomycin-Resistant Citrobacter freundii Exposure on the Microbial Community Structure in Soil

    PubMed Central

    Cycoń, Mariusz; Borymski, Sławomir; Orlewska, Kamila; Wąsik, Tomasz J.; Piotrowska-Seget, Zofia

    2016-01-01

    The occurrence of antibiotics and antibiotic resistance genes in the environment has become a subject of growing concern. The extensive use of vancomycin and other pharmaceuticals may alter the biodiversity of soil microbial communities and select antibiotic-resistant bacteria. Therefore, the purpose of the study was to evaluate the impact of vancomycin and/or vancomycin-resistant Citrobacter freundii on soil microbial communities using the denaturing gradient gel electrophoresis (DGGE) and the phospholipid fatty acid (PLFA) approaches. The experiment had a completely randomized block design with the following treatments: control soil (C), soil with vancomycin (1 mg/kg soil—VA1), soil with vancomycin (10 mg/kg soil—VA10), soil with C. freundii (Cit), soil with vancomycin (1 mg/kg soil) and C. freundii (VA1+Cit), and soil with vancomycin (10 mg/kg soil) and C. freundii (VA10+Cit). A bacterial strain resistant to vancomycin was isolated from raw sewage collected from the municipal sewage treatment plant. The obtained results indicated that the antibiotic and/or the bacterial strain exerted a selective pressure that resulted in qualitative and quantitative changes in the population of soil microorganisms. However, a multivariate analysis showed that the genetic and structural diversity of the soil microbial community was primarily affected by the incubation time and to a lesser extent by the antibiotic and introduced bacteria. DGGE analysis clearly showed that certain species within the bacterial community were sensitive to vancomycin as was evidenced by a decrease in the values of S (richness) and H (Shannon-Wiener) indices. Moreover, a PLFA method-based analysis revealed alterations in the structure of the soil microbial community as indicated by changes in the biomass of the PLFA biomarkers specific for Gram-positive and Gram-negative bacteria as well as fungi. The changes observed in the community of soil microorganisms may decrease the rate of microbial

  2. An Analysis of the Effects of Vancomycin and/or Vancomycin-Resistant Citrobacter freundii Exposure on the Microbial Community Structure in Soil.

    PubMed

    Cycoń, Mariusz; Borymski, Sławomir; Orlewska, Kamila; Wąsik, Tomasz J; Piotrowska-Seget, Zofia

    2016-01-01

    The occurrence of antibiotics and antibiotic resistance genes in the environment has become a subject of growing concern. The extensive use of vancomycin and other pharmaceuticals may alter the biodiversity of soil microbial communities and select antibiotic-resistant bacteria. Therefore, the purpose of the study was to evaluate the impact of vancomycin and/or vancomycin-resistant Citrobacter freundii on soil microbial communities using the denaturing gradient gel electrophoresis (DGGE) and the phospholipid fatty acid (PLFA) approaches. The experiment had a completely randomized block design with the following treatments: control soil (C), soil with vancomycin (1 mg/kg soil-VA1), soil with vancomycin (10 mg/kg soil-VA10), soil with C. freundii (Cit), soil with vancomycin (1 mg/kg soil) and C. freundii (VA1+Cit), and soil with vancomycin (10 mg/kg soil) and C. freundii (VA10+Cit). A bacterial strain resistant to vancomycin was isolated from raw sewage collected from the municipal sewage treatment plant. The obtained results indicated that the antibiotic and/or the bacterial strain exerted a selective pressure that resulted in qualitative and quantitative changes in the population of soil microorganisms. However, a multivariate analysis showed that the genetic and structural diversity of the soil microbial community was primarily affected by the incubation time and to a lesser extent by the antibiotic and introduced bacteria. DGGE analysis clearly showed that certain species within the bacterial community were sensitive to vancomycin as was evidenced by a decrease in the values of S (richness) and H (Shannon-Wiener) indices. Moreover, a PLFA method-based analysis revealed alterations in the structure of the soil microbial community as indicated by changes in the biomass of the PLFA biomarkers specific for Gram-positive and Gram-negative bacteria as well as fungi. The changes observed in the community of soil microorganisms may decrease the rate of microbial

  3. Mechanistic deductions from kinetic isotope effects and pH studies of pyridoxal phosphate dependent carbon-carbon lyases: Erwinia herbicola and Citrobacter freundii tyrosine phenol-lyase

    SciTech Connect

    Kiick, D.M.; Phillips, R.S.

    1988-09-20

    The pH dependence of the kinetic parameters and primary deuterium isotope effects have been determined for tyrosine phenol-lyase from both Erwinia herbicola and Citrobacter freundii. The primary deuterium isotope effects indicate that proton abstraction from the 2-position of the substrate is partially rate-limiting for both enzymes. The C. freundii enzyme primary deuterium isotope effects (DV = 3.5 and D(V/Ktyr) = 2.5) are pH independent, indicating that tyrosine is not sticky (i.e., does not dissociate slower than it reacts to give products). Since Vmax for both tyrosine and the alternate substrate S-methyl-L-cysteine is also pH independent, substrate binds only to the correctly protonated form of the enzyme. For the E. herbicola enzyme, both Vmax and V/K for tyrosine or S-methyl-L-cysteine are pH dependent, as well as both DV and D(V/Ktyr). Thus, while both the protonated and unprotonated enzyme can bind substrate, and may be interconverted directly, only the unprotonated Michaelis complex is catalytically competent. At pH 9.5, DV = 2.5 and D(V/Ktyr) = 1.5. However, at pH 6.4 the isotope effect on both parameters is equal to 4.1. From these data, the forward commitment factor (cf = 5.2) and catalytic ratio (cvf = 1.1) for tyrosine and S-methyl-L-cysteine (cf = 2.2, cvf = 24) are calculated. Also, the Michaelis complex partition ratio (cf/cvf) for substrate and products is calculated to be 4.7 for tyrosine and 0.1 for S-methyl-L-cysteine.

  4. The Type VI Secretion System Modulates Flagellar Gene Expression and Secretion in Citrobacter freundii and Contributes to Adhesion and Cytotoxicity to Host Cells.

    PubMed

    Liu, Liyun; Hao, Shuai; Lan, Ruiting; Wang, Guangxia; Xiao, Di; Sun, Hui; Xu, Jianguo

    2015-07-01

    The type VI secretion system (T6SS) as a virulence factor-releasing system contributes to virulence development of various pathogens and is often activated upon contact with target cells. Citrobacter freundii strain CF74 has a complete T6SS genomic island (GI) that contains clpV, hcp-2, and vgr T6SS genes. We constructed clpV, hcp-2, vgr, and T6SS GI deletion mutants in CF74 and analyzed their effects on the transcriptome overall and, specifically, on the flagellar system at the levels of transcription and translation. Deletion of the T6SS GI affected the transcription of 84 genes, with 15 and 69 genes exhibiting higher and lower levels of transcription, respectively. Members of the cell motility class of downregulated genes of the CF74ΔT6SS mutant were mainly flagellar genes, including effector proteins, chaperones, and regulators. Moreover, the production and secretion of FliC were also decreased in clpV, hcp-2, vgr, or T6SS GI deletion mutants in CF74 and were restored upon complementation. In swimming motility assays, the mutant strains were found to be less motile than the wild type, and motility was restored by complementation. The mutant strains were defective in adhesion to HEp-2 cells and were restored partially upon complementation. Further, the CF74ΔT6SS, CF74ΔclpV, and CF74Δhcp-2 mutants induced lower cytotoxicity to HEp-2 cells than the wild type. These results suggested that the T6SS GI in CF74 regulates the flagellar system, enhances motility, is involved in adherence to host cells, and induces cytotoxicity to host cells. Thus, the T6SS plays a wide-ranging role in C. freundii.

  5. Complex integrons containing qnrB4-ampC (bla(DHA-1)) in plasmids of multidrug-resistant Citrobacter freundii from wastewater.

    PubMed

    Yim, Grace; Kwong, Waldan; Davies, Julian; Miao, Vivian

    2013-02-01

    Microbial populations in wastewater treatment plants (WWTPs) are increasingly being recognized as environmental reservoirs of antibiotic resistance genes. PCR amplicons for plasmid-mediated quinolone resistance determinants qnrA, qnrB, and qnrS were recorded in samples from a WWTP in Vancouver, British Columbia. Six strains of ciprofloxacin-resistant Citrobacter freundii were isolated and found to carry mutations in gyrA and parC, as well as multiple plasmid-borne resistance genes, collectively including qnrB; aac(6')-Ib-cr; β-lactamase-encoding genes from molecular classes A (blaTEM-1), C (ampC), D (blaOXA-1, blaOXA-10); and genes for resistance to 5 other types of antibiotics. In 3 strains, large (>60 kb) plasmids carried qnrB4 and ampC as part of a complex integron in a 14 kb arrangement that has been reported worldwide but, until recently, only among pathogenic strains of Klebsiella. Analysis of single-nucleotide polymorphisms in the qnrB4-ampC regions infers 2 introductions into the WWTP environment. These results suggest recent passage of plasmid-borne fluoroquinolone and β-lactam resistance genes from pathogens to bacteria that may be indigenous inhabitants of WWTPs, thus contributing to an environmental pool of antibiotic resistance.

  6. Kinetic Parameters and Cytotoxic Activity of Recombinant Methionine γ-Lyase from Clostridium tetani, Clostridium sporogenes, Porphyromonas gingivalis and Citrobacter freundii.

    PubMed

    Morozova, E A; Kulikova, V V; Yashin, D V; Anufrieva, N V; Anisimova, N Y; Revtovich, S V; Kotlov, M I; Belyi, Y F; Pokrovsky, V S; Demidkina, T V

    2013-07-01

    The steady-state kinetic parameters of pyridoxal 5'-phosphate-dependent recombinant methionine γ -lyase from three pathogenic bacteria, Clostridium tetani, Clostridium sporogenes, and Porphyromonas gingivalis, were determined in β- and γ-elimination reactions. The enzyme from C. sporogenes is characterized by the highest catalytic efficiency in the γ-elimination reaction of L-methionine. It was demonstrated that the enzyme from these three sources exists as a tetramer. The N-terminal poly-histidine fragment of three recombinant enzymes influences their catalytic activity and facilitates the aggregation of monomers to yield dimeric forms under denaturing conditions. The cytotoxicity of methionine γ-lyase from C. sporogenes and C. tetani in comparison with Citrobacter freundii was evaluated using K562, PC-3, LnCap, MCF7, SKOV-3, and L5178y tumor cell lines. K562 (IC50=0.4-1.3 U/ml), PC-3 (IC50=0.1-0.4 U/ml), and MCF7 (IC50=0.04-3.2 U/ml) turned out to be the most sensitive cell lines.

  7. Secondary metabolites extracted from marine sponge associated Comamonas testosteroni and Citrobacter freundii as potential antimicrobials against MDR pathogens and hypothetical leads for VP40 matrix protein of Ebola virus: an in vitro and in silico investigation.

    PubMed

    Skariyachan, Sinosh; Acharya, Archana B; Subramaniyan, Saumya; Babu, Sumangala; Kulkarni, Shruthi; Narayanappa, Rajeswari

    2016-09-01

    The current study explores therapeutic potential of metabolites extracted from marine sponge (Cliona sp.)-associated bacteria against MDR pathogens and predicts the binding prospective of probable lead molecules against VP40 target of Ebola virus. The metabolite-producing bacteria were characterized by agar overlay assay and as per the protocols in Bergey's manual of determinative bacteriology. The antibacterial activities of extracted metabolites were tested against clinical pathogens by well-diffusion assay. The selected metabolite producers were characterized by 16S rDNA sequencing. Chemical screening and Fourier Transform Infrared (FTIR) analysis for selected compounds were performed. The probable lead molecules present in the metabolites were hypothesized based on proximate analysis, FTIR data, and literature survey. The drug-like properties and binding potential of lead molecules against VP40 target of Ebola virus were hypothesized by computational virtual screening and molecular docking. The current study demonstrated that clear zones around bacterial colonies in agar overlay assay. Antibiotic sensitivity profiling demonstrated that the clinical isolates were multi-drug resistant, however; most of them showed sensitivity to secondary metabolites (MIC-15 μl/well). The proximate and FTIR analysis suggested that probable metabolites belonged to alkaloids with O-H, C-H, C=O, and N-H groups. 16S rDNA characterization of selected metabolite producers demonstrated that 96% and 99% sequence identity to Comamonas testosteroni and Citrobacter freundii, respectively. The docking studies suggested that molecules such as Gymnastatin, Sorbicillactone, Marizomib, and Daryamide can designed as probable lead candidates against VP40 target of Ebola virus.

  8. Mechanistic evaluation of MelA α-galactosidase from Citrobacter freundii: a family 4 glycosyl hydrolase in which oxidation is rate-limiting.

    PubMed

    Chakladar, Saswati; Cheng, Lydia; Choi, Mary; Liu, James; Bennet, Andrew J

    2011-05-24

    The MelA gene from Citrobacter freundii, which encodes a glycosyl hydrolase family 4 (GH4) α-galactosidase, has been cloned and expressed in Escherichia coli. The recombinant enzyme catalyzes the hydrolysis of phenyl α-galactosides via a redox elimination-addition mechanism involving oxidation of the hydroxyl group at C-3 and elimination of phenol across the C-1-C-2 bond to give an enzyme-bound glycal intermediate. For optimal activity, the MelA enzyme requires two cofactors, NAD(+) and Mn(2+), and the addition of a reducing agent, such as mercaptoethanol. To delineate the mechanism of action for this GH4 enzyme, we measured leaving group effects, and the derived β(lg) values on V and V/K are indistinguishable from zero (-0.01 ± 0.02 and 0.02 ± 0.04, respectively). Deuterium kinetic isotope effects (KIEs) were measured for the weakly activated substrate phenyl α-D-galactopyranoside in which isotopic substitution was incorporated at C-1, C-2, or C-3. KIEs of 1.06 ± 0.07, 0.91 ± 0.04, and 1.02 ± 0.06 were measured on V for the 1-(2)H, 2-(2)H, and 3-(2)H isotopic substrates, respectively. The corresponding values on V/K were 1.13 ± 0.07, 1.74 ± 0.06, and 1.74 ± 0.05, respectively. To determine if the KIEs report on a single step or on a virtual transition state, we measured KIEs using doubly deuterated substrates. The measured (D)V/K KIEs for MelA-catalyzed hydrolysis of phenyl α-D-galactopyranoside on the dideuterated substrates, (D)V/K((3-D)/(2-D,3-D)) and (D)V/K((2-D)/(2-D,3-D)), are 1.71 ± 0.12 and 1.71 ± 0.13, respectively. In addition, the corresponding values on V, (D)V((3-D)/(2-D,3-D)) and (D)V((2-D)/(2-D,3-D)), are 0.91 ± 0.06 and 1.01 ± 0.06, respectively. These observations are consistent with oxidation at C-3, which occurs via the transfer of a hydride to the on-board NAD(+), being concerted with proton removal at C-2 and the fact that this step is the first irreversible step for the MelA α-galactosidase-catalyzed reactions of aryl

  9. Transferable class C beta-lactamases in Escherichia coli strains isolated in Greek hospitals and characterization of two enzyme variants (LAT-3 and LAT-4) closely related to Citrobacter freundii AmpC beta-lactamase.

    PubMed

    Gazouli, M; Tzouvelekis, L S; Vatopoulos, A C; Tzelepi, E

    1998-10-01

    Among 2133 isolates of Escherichia coli obtained during 1996 from 10 Greek hospitals, 63 (3%) were resistant to cefoxitin. Typing by ERIC2-PCR indicated that the cefoxitin-resistant (FOXr) isolates were distinct. beta-Lactamase studies and hybridization experiments showed that most strains produced beta-lactamases related to the AmpC chromosomal cephalosporinase of Citrobacter freundii. The enzymes were encoded by similar non-self-transmissible plasmids. The bla genes encoding two beta-lactamases (LAT-3 and LAT-4) with isoelectric points 8.9 and 9.4, respectively, were cloned and sequenced. The deduced amino acid sequences displayed a high degree of homology (>95%) with the AmpC beta-lactamase of C. freundii. The patterns of resistance to beta-lactams of the FOXr E. coli depended on the quantity of class C enzymes and the simultaneous expression of other beta-lactamases. In a few isolates a 36 kDa outer-membrane protein, presumably a porin, was not expressed at detectable quantities. These isolates were resistant to cefoxitin, and their susceptibility to the other beta-lactams tested was not significantly decreased.

  10. Evaluation of Phoenix Automated Microbiology System for detecting extended-spectrum beta-lactamases among chromosomal AmpC-producing Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, and Serratia marcescens.

    PubMed

    Park, Yeon-Joon; Yu, Jin Kyung; Lee, Seungok; Park, Jung-Jun; Oh, Eun-Jee

    2007-01-01

    We evaluated the BD Phoenix Extended-Spectrum beta-Lactamase (ESBL) detection test among chromosomal AmpC-producing Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, and Serratia marcescens. The study was conducted on 72 non-repetitive ESBL producers (33 E. cloacae, 13 E. aerogenes, 14 C. freundii, and 12 S. marcescens) and 77 ESBL non-producers (33 E. cloacae, 9 E. aerogenes, 6 C. freundii, and 29 S. marcescens). The organisms were selected as suspected ESBL-producers based on the double disk synergy test and confirmed by PCR amplification of blaTEM-1, blaSHV-1, blaCTX-M-1, blaCTX-M-2, and blaCTX-M-9. The Phoenix ESBL test, using a 5-well confirmatory test and the BDXpert system, was evaluated. Of the 72 isolates identified as ESBL-producers based on the DDST, 46 isolates harbored CTX-M-type enzymes, 21 harbored TEM type enzymes, and 31 harbored SHV enzymes. The Phoenix system identified ESBL only in 15 isolates. Of the 77 ESBL non-producers, ths Phoenix system identified ESBL in 4 isolates, 3 of which were confirmed to be ESBL-producers. In this study, the Phoenix system was highly specific (76/77, 98.7%), and it identified 3 additional ESBL-producers that were not detected by DDST. However, the Phoenix system's sensitivity was very low (15/72, 20.8%). Considering the increasing prevalence of ESBL production among AmpC-producers, the BD Phoenix system could not be considered a reliable stand-alone ESBL detection method for the strains tested in our study.

  11. Inducible expression of the chromosomal cdiA from Citrobacter diversus NF85, encoding an ambler class A beta-lactamase, is under similar genetic control to the chromosomal ampC, encoding an ambler class C enzyme, from Citrobacter freundii OS60.

    PubMed

    Jones, M E; Bennett, P M

    1995-01-01

    This study aimed to characterize the molecular basis of beta-lactamase induction in Citrobacter diversus. The chromosomal beta-lactamase encoding region from C. diversus, strain NF85, was cloned and expressed in Escherichia coli. The cloned region was sequenced and open-reading frames encoding a class A beta-lactamase, designated cdiA, and a putative LysR-type transcriptional regulator protein, divergently transcribed from the beta-lactamase gene and designated cdiR, were identified. The nucleotide sequence of the NF85 cdiA was identical to that of the published C. diversus ULA27 ampC sequence. A putative helix-turn-helix DNA-binding motif was located at the N-terminus of CdiR, and homology with enterobacterial AmpR proteins was noted. CdiR was demonstrated to bind to the C. diversus cdiAR intergenic region but not to the C. freundii ampCR intergenic region. A putative CdiR binding motif was identified in the cdiAR intergenic region. The cloned cdiAR region was inducible in E. coli strains SNO3 and HfrH. The inducible phenotype was dependent on the E. coli ampD and ampG gene products. We conclude that the molecular basis of inducible cdiA expression in C. diversus is similar to that of C. freundii ampC.

  12. Draft Genome Sequences of Pseudomonas aeruginosa Strain PS3 and Citrobacter freundii Strain SA79 Obtained from a Wound Dressing-Associated Biofilm.

    PubMed

    Akbar, Sirwan; Rout, Simon P; Humphreys, Paul N

    2015-01-01

    Two isolates, one from the genus Pseudomonas and the second from Citrobacter, were isolated from a wound dressing-associated biofilm. Following whole-genome sequencing, the two isolates presented genes encoding for resistance to antibiotics and those involved in exopolysaccharide production.

  13. Binding of the Citrobacter freundii AmpR regulator to a single DNA site provides both autoregulation and activation of the inducible ampC beta-lactamase gene.

    PubMed Central

    Lindquist, S; Lindberg, F; Normark, S

    1989-01-01

    Citrobacter freundii encodes an inducible chromosomal beta-lactamase. Induction requires the product of the ampR gene, which is transcribed in the opposite orientation from the ampC beta-lactamase gene. We show here that the AmpR protein acts as a transcriptional activator by binding to a DNA region immediately upstream of the ampC promoter. The DNase I footprint pattern was not affected by growth in the presence of beta-lactam inducer or by the use of extracts prepared from cells carrying the ampD2 allele leading to semiconstitutive production of beta-lactamase. It is suggested that activation of AmpR facilitates binding or open complex formation for RNA polymerase at the ampC promoter. The AmpR-binding site overlaps the ampR promoter, and beta-galactosidase activity was decreased from an ampR-lacZ transcriptional fusion when AmpR was expressed from a coresident plasmid, suggesting that ampR is autogenously controlled. The AmpR protein belongs to a family of highly homologous transcriptional activators that includes LysR, which regulates the E. coli lysine synthetase gene, and the NodD protein, which regulates expression of a number of genes involved in nodulation in Rhizobium. The lack of sequence homology to any known beta-lactam-binding protein suggests that AmpR does not bind directly to the beta-lactam inducer but interacts with a second messenger of unknown nature. Images PMID:2786868

  14. Characterization of qnrB-like genes in Citrobacter species of the American Type Culture Collection.

    PubMed

    Saga, Tomoo; Sabtcheva, Stefana; Mitsutake, Kotaro; Ishii, Yoshikazu; Tateda, Kazuhiro; Yamaguchi, Keizo; Kaku, Mitsuo

    2013-06-01

    Among five American Type Culture Collection (ATCC) Citrobacter strains, qnrB60 in Citrobacter freundii ATCC 6879, an isolate from the preantibiotic era, and qnrB61 in Citrobacter braakii ATCC 51113(T), a type strain belonging to the C. freundii complex, were identified. Meanwhile, a truncated qnrB-like pseudogene was identified in C. freundii ATCC 8090(T) and ATCC 43864. No qnrB-like sequence was found in Citrobacter koseri ATCC 27028(T). These findings underscore the close relationship between this species and qnrB.

  15. [NMR screening of potential inhibitors of Citrobacter freundii methionine].

    PubMed

    Batuev, E A; Lizunov, A Iu; Morozova, E A; Klochkov, V V; Anufrieva, N V; Demidkina, T V; Pol'shakov, V I

    2014-01-01

    Methionine γ-lyase [EC 4.4.1.11] participates in a methionine catabolism at a number of bacteria and protozoa eukaryotes, including pathogenic microorganisms. Lack of this enzyme at mammals allows consider it as a perspective target for rational antibacterial drug design. Currently in medical practice there are no the preparations based on an inhibition of methionine γ-lyase activity. We present results of the search of potential inhibitors of the enzyme using the NMR screening techniques based on identification of compounds, which able to bind specifically to their biological target. Study included a stage of in silico virtual screening of the library of commercially available compounds and subsequent experimental selection of the leading compounds, capable to interact with enzyme. Identification of binding was carried out by means of saturation transfer difference (STD) spectroscopy and WaterLOGSY technique. At the final stage the experimental assessment of inhibiting ability of the selected compounds in the reaction of γ-elimination of L-methionine catalyzed by methionine γ-lyase was carried out. Binding constants of two leading compounds were determined using the WaterLOGSY method. The research expands structural group of potential inhibitors of methionine γ-lyase and allows approach to the design of the inhibitors with higher efficacy.

  16. Multidrug resistant citrobacter: an unusual cause of liver abscess.

    PubMed

    Kumar, Prabhat; Ghosh, Soumik; Rath, Deepak; Gadpayle, A K

    2013-01-01

    Liver abscesses are infectious, space occupying lesions in the liver, the two most common abscesses being pyogenic and amoebic. A pyogenic liver abscess (PLA) is a rare condition with a reported incidence of 20 per 100 000 hospital admissions in the western population. The right lobe of the liver is the most common site in both types of liver abscess. Clinical presentation is elusive with complaints of fever, right upper quadrant pain in the abdomen and hepatomegaly with or without jaundice. The aetiology of PLA has changed in the past few decades and may be of biliary, portal, arterial or traumatic origin, but many cases are still cryptogenic. The most common organisms causing PLA are Gram-negative aerobes, especially Escherichia coli and Klebsiella pneumoniae. Studies have shown a high degree of antimicrobial susceptibility of isolated organism resulting in an overall lower mortality in PLA. Here, we present a case of PLA caused by multidrug-resistant Citrobacter freundii, which is an unusual organism to be isolated.

  17. Brain abscess caused by Citrobacter koseri infection in an adult.

    PubMed

    Liu, Heng-Wei; Chang, Chih-Ju; Hsieh, Cheng-Ta

    2015-04-01

    Citrobacter koseri is a gram-negative bacillus that causes mostly meningitis and brain abscesses in neonates and infants. However, brain abscess caused by Citrobacter koseri infection in an adult is extremely rare, and only 2 cases have been described. Here, we reported a 73-year-old male presenting with a 3-week headache. A history of diabetes mellitus was noted. The images revealed a brain abscess in the left frontal lobe and pus culture confirmed the growth of Citrobacter koseri. The clinical symptoms improved completely postoperatively.

  18. [Identification of Citrobacter species and their occurrence in raw products and foods].

    PubMed

    Urbanová, E; Pácová, Z

    1997-03-01

    Fifty-nine strains of bacteria were tested in study that were isolated from raw materials and foods (raw milk, farm milking parlors, sausage meat, raw potatoes, cheese, frozen oven-ready foods, confectionery products, cold dishes), and they were included in the genus Citrobacter using a commercial diagnostic kit ENTEROtest 16 (Lachema a.s., Brno), numeric identification program TNW (Czech Collection of Microorganisms, Faculty of Science of Masaryk University at Brno) and identification key (O'Hara et al., 1995). The results of the ENTEROtest itself, including OXI and ONPtests, did not provide satisfactory discrimination of detected strains to the level of species since 64.4% were identified by the genus by TNW program or designated as intermediary strains. Correct species identification was obtained in 33.9% only (Tab. I). Five next conventional tests (dulcitol, alpha-methyl-glucoside, raffinose, melibiose, arginine dihydrolase) were used and their results successfully specified 94.9% tested strains to the species level (Tab. I). A dichotomic identification key (O'Hara et al., 1995) enabled to classify the strains on the basis of the results of ENTEROtest 16 and two conventional tests (dulcitol, melibiosis) relatively easily, and it can be recommended for routine identification of typical Citrobacters from foods. Only ten strains were classified in a wrong way (16.9%) due to false results in ENTEROtest (Tab. II). Tab. III shows the strains classified wrongly by both identifications systems. The tested set contained Citrobacter braakii in a majority of cases (30 strains), followed by C. freundii (17 strains), C. youngae (6 strains), 2 strains of genomospecies 10 and one strain of C. koseri, C. amalonaticus and C farmeri. Tab. IV shows the presence of Citrobacter species in the particular raw materials and foods. The most frequently present species in raw materials: C. braakii (26 strains, 68.4%), C. freundii (3 strains, 7.9%) and C. youngae (3 strains, 7.9%). Foods

  19. Phylogeny and Comparative Genomics Unveil Independent Diversification Trajectories of qnrB and Genetic Platforms within Particular Citrobacter Species

    PubMed Central

    Ribeiro, Teresa G.; Novais, Ângela; Branquinho, Raquel; Machado, Elisabete

    2015-01-01

    To gain insights into the diversification trajectories of qnrB genes, a phylogenetic and comparative genomics analysis of these genes and their surrounding genetic sequences was performed. For this purpose, Citrobacter sp. isolates (n = 21) and genome or plasmid sequences (n = 56) available in public databases harboring complete or truncated qnrB genes were analyzed. Citrobacter species identification was performed by phylogenetic analysis of different genotypic markers. The clonal relatedness among isolates, the location of qnrB genes, and the genetic surroundings of qnrB genes were investigated by pulsed-field gel electrophoresis (PFGE), S1-/I-CeuI-PFGE and hybridization, and PCR mapping and sequencing, respectively. Identification of Citrobacter isolates was achieved using leuS and recN gene sequences, and isolates characterized in this study were diverse and harbored chromosomal qnrB genes. Phylogenetic analysis of all known qnrB genes revealed seven main clusters and two branches, with most of them included in two clusters. Specific platforms (comprising pspF and sapA and varying in synteny and/or identity of other genes and intergenic regions) were associated with each one of these qnrB clusters, and the reliable identification of all Citrobacter isolates revealed that each platform evolved in different recognizable (Citrobacter freundii, C. braakii, C. werkmanii, and C. pasteurii) and putatively new species. A high identity was observed between some of the platforms identified in the chromosome of Citrobacter spp. and in different plasmids of Enterobacteriaceae. Our data corroborate Citrobacter as the origin of qnrB and further suggest divergent evolution of closely related qnrB genes/platforms in particular Citrobacter spp., which were delineated using particular genotypic markers. PMID:26169406

  20. Phylogeny and Comparative Genomics Unveil Independent Diversification Trajectories of qnrB and Genetic Platforms within Particular Citrobacter Species.

    PubMed

    Ribeiro, Teresa G; Novais, Ângela; Branquinho, Raquel; Machado, Elisabete; Peixe, Luísa

    2015-10-01

    To gain insights into the diversification trajectories of qnrB genes, a phylogenetic and comparative genomics analysis of these genes and their surrounding genetic sequences was performed. For this purpose, Citrobacter sp. isolates (n = 21) and genome or plasmid sequences (n = 56) available in public databases harboring complete or truncated qnrB genes were analyzed. Citrobacter species identification was performed by phylogenetic analysis of different genotypic markers. The clonal relatedness among isolates, the location of qnrB genes, and the genetic surroundings of qnrB genes were investigated by pulsed-field gel electrophoresis (PFGE), S1-/I-CeuI-PFGE and hybridization, and PCR mapping and sequencing, respectively. Identification of Citrobacter isolates was achieved using leuS and recN gene sequences, and isolates characterized in this study were diverse and harbored chromosomal qnrB genes. Phylogenetic analysis of all known qnrB genes revealed seven main clusters and two branches, with most of them included in two clusters. Specific platforms (comprising pspF and sapA and varying in synteny and/or identity of other genes and intergenic regions) were associated with each one of these qnrB clusters, and the reliable identification of all Citrobacter isolates revealed that each platform evolved in different recognizable (Citrobacter freundii, C. braakii, C. werkmanii, and C. pasteurii) and putatively new species. A high identity was observed between some of the platforms identified in the chromosome of Citrobacter spp. and in different plasmids of Enterobacteriaceae. Our data corroborate Citrobacter as the origin of qnrB and further suggest divergent evolution of closely related qnrB genes/platforms in particular Citrobacter spp., which were delineated using particular genotypic markers.

  1. Distribution of chitin/chitosan-like bioflocculant-producing potential in the genus Citrobacter.

    PubMed

    Kimura, Kazuyuki; Inoue, Takuya; Kato, Dai-Ichiro; Negoro, Seiji; Ike, Michihiko; Takeo, Masahiro

    2013-11-01

    Some strains belonging to the genera Citrobacter and Enterobacter have been reported to produce chitin/chitosan-like bioflocculants (BFs) from acetate. In this study, to investigate the distribution of the BF-producing potential in the genus Citrobacter and to screen stably and highly BF-producing strains, we obtained 36 Citrobacter strains from different culture collection centers, which were distributed among seven species in the genus, and tested for the flocculating activities of their culture supernatants using a kaolin suspension method. As a result, 21 strains belonging to C. freundii (17 strains in 23 strains tested), C. braakii (two in two), C. youngae (one in one), and C. werkmanii (one in two) showed flocculating activity, but this ability was limited to cells grown on acetate. Gas chromatography/mass spectrometry (GC/MS) analysis of the hydrolysates from the BFs of five selected strains indicated that they consisted of glucosamine and/or N-acetylglucosamine, such as the chitin/chitosan-like BF (BF04) produced by Citrobacter sp. TKF04 (Fujita et al. J Biosci Bioeng 89: 40-46, 2000). Gel filtration chromatography using a high-performance liquid chromatography system revealed that the molecular weight ranges of these BFs varied, but the average sizes were all above 1.66 × 10⁶Da.

  2. Unraveling the dha cluster in Citrobacter werkmanii: comparative genomic analysis of bacterial 1,3-propanediol biosynthesis clusters.

    PubMed

    Maervoet, Veerle E T; De Maeseneire, Sofie L; Soetaert, Wim K; De Mey, Marjan

    2014-04-01

    In natural 1,3-propanediol (PDO) producing microorganisms such as Klebsiella pneumoniae, Citrobacter freundii and Clostridium sp., the genes coding for PDO producing enzymes are grouped in a dha cluster. This article describes the dha cluster of a novel candidate for PDO production, Citrobacter werkmanii DSM17579 and compares the cluster to the currently known PDO clusters of Enterobacteriaceae and Clostridiaceae. Moreover, we attribute a putative function to two previously unannotated ORFs, OrfW and OrfY, both in C. freundii and in C. werkmanii: both proteins might form a complex and support the glycerol dehydratase by converting cob(I)alamin to the glycerol dehydratase cofactor coenzyme B12. Unraveling this biosynthesis cluster revealed high homology between the deduced amino acid sequence of the open reading frames of C. werkmanii DSM17579 and those of C. freundii DSM30040 and K. pneumoniae MGH78578, i.e., 96 and 87.5 % identity, respectively. On the other hand, major differences between the clusters have also been discovered. For example, only one dihydroxyacetone kinase (DHAK) is present in the dha cluster of C. werkmanii DSM17579, while two DHAK enzymes are present in the cluster of K. pneumoniae MGH78578 and Clostridium butyricum VPI1718.

  3. Biohydrogen production by dark fermentation of glycerol using Enterobacter and Citrobacter Sp.

    PubMed

    Maru, Biniam T; Constanti, Magda; Stchigel, Alberto M; Medina, Francesc; Sueiras, Jesus E

    2013-01-01

    Glycerol is an attractive substrate for biohydrogen production because, in theory, it can produce 3 mol of hydrogen per mol of glycerol. Moreover, glycerol is produced in substantial amounts as a byproduct of producing biodiesel, the demand for which has increased in recent years. Therefore, hydrogen production from glycerol was studied by dark fermentation using three strains of bacteria: namely, Enterobacter spH1, Enterobacter spH2, and Citrobacter freundii H3 and a mixture thereof (1:1:1). It was found that, when an initial concentration of 20 g/L of glycerol was used, all three strains and their mixture produced substantial amounts of hydrogen ranging from 2400 to 3500 mL/L, being highest for C. freundii H3 (3547 mL/L) and Enterobacter spH1 (3506 mL/L). The main nongaseous fermentation products were ethanol and acetate, albeit in different ratios. For Enterobacter spH1, Enterobacter spH2, C. freundii H3, and the mixture (1:1:1), the ethanol yields (in mol EtOH/mol glycerol consumed) were 0.96, 0.67, 0.31, and 0.66, respectively. Compared to the individual strains, the mixture (1:1:1) did not show a significantly higher hydrogen level, indicating that there was no synergistic effect. Enterobacter spH1 was selected for further investigation because of its higher yield of hydrogen and ethanol.

  4. Citrobacter rodentium: infection, inflammation and the microbiota.

    PubMed

    Collins, James W; Keeney, Kristie M; Crepin, Valerie F; Rathinam, Vijay A K; Fitzgerald, Katherine A; Finlay, B Brett; Frankel, Gad

    2014-09-01

    Citrobacter rodentium is a mucosal pathogen of mice that shares several pathogenic mechanisms with enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC), which are two clinically important human gastrointestinal pathogens. Thus, C. rodentium has long been used as a model to understand the molecular basis of EPEC and EHEC infection in vivo. In this Review, we discuss recent studies in which C. rodentium has been used to study mucosal immunology, including the deregulation of intestinal inflammatory responses during bacteria-induced colitis and the role of the intestinal microbiota in mediating resistance to colonization by enteric pathogens. These insights should help to elucidate the roles of mucosal inflammatory responses and the microbiota in the virulence of enteric pathogens.

  5. Citrobacter bitternis sp. nov. isolated from bitterns.

    PubMed

    Ko, Kwan Soo; Choi, Ji-Young; Kim, Joo; Park, Myoung Kyu

    2015-06-01

    In this study, we reported two gram-negative bacteria that were isolated from bitterns, designated as SKKU-TP7(T) and SKKU-TP20, representing a novel species of Citrobacter. Based on the 16S rRNA gene sequences, the two strains were found to be closely related and showed the highest pairwise similarity with Citrobacter farmeri CDC 2992-81(T) (97.1-97.3 %) and other Citrobacter species. Cellular fatty acid analysis revealed that the profiles of strains SKKU-TP7(T) and SKKU-TP20 were similar to those of related species of Citrobacter. The major cellular fatty acids were C16:0 (31.5 %), summed feature 3 (C16:1 ω7c, C16:1 ω6c, 19.7 %), summed feature 8 (C18:1 ω7c, C18:1 ω6c, 11.9 %), C17:0 cyclo (10.7 %), and summed feature 2 (C12:0 aldehyde/unknown 10928, 9.5 %). Although the strains could utilize sucrose and raffinose as a carbon source, they did not produce ornithine decarboxylase and urease. The biochemical and genotypic characteristics indicate that strains SKKU-TP7(T) and SKKU-TP20 represent a novel species of Citrobacter, for which the name Citrobacter bitterns sp. nov. is proposed. The type strain is SKKU-TP7(T) (=KCTC 42139(T) = JCM 30009(T)).

  6. Clinical isolates of Enterobacteriaceae producing extended-spectrum beta-lactamases: prevalence of CTX-M-3 at a hospital in China.

    PubMed

    Wang, Hui; Kelkar, Swathi; Wu, Weiyuan; Chen, Minjun; Quinn, John P

    2003-02-01

    The prevalence of extended-spectrum beta-lactamase-producing strains was demonstrated in 5 of 44 (11.4%) Escherichia coli, 17 of 43 (39.5%) Klebsiella pneumoniae, 3 of 50 (6.0%) Enterobacter cloacae, and 2 of 25 (8.0%) Citrobacter freundii strains at a teaching hospital in China. Nineteen of these 27 strains expressed CTX-M-3 beta-lactamase (pI 8.6). A subset of the clinical isolates expressing the CTX-M-3 enzyme, tested by pulsed-field gel electrophoresis, revealed multiple clones. Five isolates expressed a novel enzyme, SHV-43 (pI 8.0), which had two substitutions (Leu113Phe and Thr149Ser) compared with SHV-1.

  7. Chromosomally Encoded AmpC-Type β-Lactamase in a Clinical Isolate of Proteus mirabilis

    PubMed Central

    Bret, L.; Chanal-Claris, C.; Sirot, D.; Chaibi, E. B.; Labia, R.; Sirot, J.

    1998-01-01

    A clinical strain of Proteus mirabilis (CF09) isolated from urine specimens of a patient displayed resistance to amoxicillin (MIC >4,096 μg/ml), ticarcillin (4,096 μg/ml), cefoxitin (64 μg/ml), cefotaxime (256 μg/ml), and ceftazidime (128 μg/ml) and required an elevated MIC of aztreonam (4 μg/ml). Clavulanic acid did not act synergistically with cephalosporins. Two β-lactamases with apparent pIs of 5.6 and 9.0 were identified by isoelectric focusing on a gel. Substrate and inhibition profiles were characteristic of an AmpC-type β-lactamase with a pI of 9.0. Amplification by PCR with primers for ampC genes (Escherichia coli, Enterobacter cloacae, and Citrobacter freundii) of a 756-bp DNA fragment from strain CF09 was obtained only with C. freundii-specific primers. Hybridization results showed that the ampC gene is only chromosomally located while the TEM gene is plasmid located. After cloning of the gene, analysis of the complete nucleotide sequence (1,146 bp) showed that this ampC gene is close to blaCMY-2, from which it differs by three point mutations leading to amino acid substitutions Glu → Gly at position 22, Trp → Arg at position 201, and Ser → Asn at position 343. AmpC β-lactamases derived from that of C. freundii (LAT-1, LAT-2, BIL-1, and CMY-2) have been found in Klebsiella pneumoniae, E. coli, and Enterobacter aerogenes and have been reported to be plasmid borne. This is the first example of a chromosomally encoded AmpC-type β-lactamase observed in P. mirabilis. We suggest that it be designated CMY-3. PMID:9593136

  8. Optimum management of Citrobacter koseri infection.

    PubMed

    Deveci, Aydin; Coban, Ahmet Yilmaz

    2014-09-01

    Low virulent Citrobacter koseri can cause life threatening infections. Neonates and other immunocompromised patients are particularly susceptible to infection from C. koseri. Any infection due to C. koseri mandates antimicrobial therapy based on the sensitivity of the pathogen microorganism. Various types of antibiotics, including aminoglycosides carbapenems, cephalosporins, chloramphenicol and quinolones, are used for the treatment of C. koseri infections. The rational choice of antimicrobial therapy for Citrobacter infections is a challenge for clinicians because there is a sustained increase in antibacterial resistance. We reviewed antimicrobial agents used for C. koseri infections in this review.

  9. Species identification of strains belonging to genus Citrobacter using the biochemical method and MALDI-TOF mass spectrometry.

    PubMed

    Kolínská, Renáta; Spanělová, Petra; Dřevínek, Michal; Hrabák, Jaroslav; Zemličková, Helena

    2015-01-01

    Strains of genus Citrobacter (152 isolates from 1950 to 1988 deposited in the Czech National Collection of Type Cultures, Prague) were re-classified using biological and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) methods. One-hundred thirty-six strains (ca. 90 %) were identified to the species level using the biological method with evaluation by Farmer matrix. MALDI-TOF MS exhibited better identification capability, the data being more compact; the method was unambiguously successful in typing 145 (95 %) strains. Comparison of the results of identification by the two methods revealed differences (for 12 samples) in identified species which, considering all biochemical and/or MS characteristics, could be attributed to the natural variability of strains and close relation of the misidentified species (all of them belonged to the Citrobacter freundii complex). Taking into account all the above data, both methods can be considered reliable; however, the MALDI-TOF MS exhibits higher accuracy, efficiency, and rapidity.

  10. Molecular analysis of type 3 fimbrial genes from Escherichia coli, Klebsiella and Citrobacter species

    PubMed Central

    2010-01-01

    Background Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial infection in the United States and is caused by a range of uropathogens. Biofilm formation by uropathogens that cause CAUTI is often mediated by cell surface structures such as fimbriae. In this study, we characterised the genes encoding type 3 fimbriae from CAUTI strains of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter koseri and Citrobacter freundii. Results Phylogenetic analysis of the type 3 fimbrial genes (mrkABCD) from 39 strains revealed they clustered into five distinct clades (A-E) ranging from one to twenty-three members. The majority of sequences grouped in clade A, which was represented by the mrk gene cluster from the genome sequenced K. pneumoniae MGH78578. The E. coli and K. pneumoniae mrkABCD gene sequences clustered together in two distinct clades, supporting previous evidence for the occurrence of inter-genera lateral gene transfer. All of the strains examined caused type 3 fimbriae mediated agglutination of tannic acid treated human erythrocytes despite sequence variation in the mrkD-encoding adhesin gene. Type 3 fimbriae deletion mutants were constructed in 13 representative strains and were used to demonstrate a direct role for type 3 fimbriae in biofilm formation. Conclusions The expression of functional type 3 fimbriae is common to many Gram-negative pathogens that cause CAUTI and is strongly associated with biofilm growth. Our data provides additional evidence for the spread of type 3 fimbrial genes by lateral gene transfer. Further work is now required to substantiate the clade structure reported here by examining more strains as well as other bacterial genera that make type 3 fimbriae and cause CAUTI. PMID:20576143

  11. Occurrence of CTX-M-3, CTX-M-15, CTX-M-14, and CTX-M-9 Extended-Spectrum β-Lactamases in Enterobacteriaceae Clinical Isolates in Korea

    PubMed Central

    Kim, Jungmin; Lim, Yu-Mi; Jeong, Young-Sook; Seol, Sung-Yong

    2005-01-01

    Among 603 isolates of Enterobacteriaceae collected between June and November 2003 from three university hospitals within Korea, blaCTX-M-3, blaCTX-M-15, blaCTX-M-14, and blaCTX-M-9 were detected in 41 isolates of species from five different genera of Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter spp., and Serratia marcescens. PMID:15793142

  12. Pre-steady-state kinetic and structural analysis of interaction of methionine γ-lyase from Citrobacter freundii with inhibitors.

    PubMed

    Kuznetsov, Nikita A; Faleev, Nicolai G; Kuznetsova, Alexandra A; Morozova, Elena A; Revtovich, Svetlana V; Anufrieva, Natalya V; Nikulin, Alexei D; Fedorova, Olga S; Demidkina, Tatyana V

    2015-01-01

    Methionine γ-lyase (MGL) catalyzes the γ-elimination of l-methionine and its derivatives as well as the β-elimination of l-cysteine and its analogs. These reactions yield α-keto acids and thiols. The mechanism of chemical conversion of amino acids includes numerous reaction intermediates. The detailed analysis of MGL interaction with glycine, l-alanine, l-norvaline, and l-cycloserine was performed by pre-steady-state stopped-flow kinetics. The structure of side chains of the amino acids is important both for their binding with enzyme and for the stability of the external aldimine and ketimine intermediates. X-ray structure of the MGL·l-cycloserine complex has been solved at 1.6 Å resolution. The structure models the ketimine intermediate of physiological reaction. The results elucidate the mechanisms of the intermediate interconversion at the stages of external aldimine and ketimine formation.

  13. Multilocus sequence analysis of the genus Citrobacter and description of Citrobacter pasteurii sp. nov.

    PubMed

    Clermont, Dominique; Motreff, Laurence; Passet, Virginie; Fernandez, José-Carlos; Bizet, Chantal; Brisse, Sylvain

    2015-05-01

    Strains originating from various sources and classified as members of the genus Citrobacter within the family Enterobacteriaceae were characterized by sequencing internal portions of genes rpoB, fusA, pyrG and leuS, 16S rRNA gene sequencing, average nucleotide identity (ANI) of genomic sequences and biochemical tests. Phylogenetic analysis based on the four housekeeping genes showed that the 11 species of the genus Citrobacter with validly published names are well demarcated. Strains CIP 55.13(T) and CIP 55.9 formed a distinct branch associated with Citrobacter youngae. The ANI between CIP 55.9 and CIP 55.13(T) was 99.19%, whereas it was 94.75% between CIP 55.13(T) and strain CIP 105016(T) of the species C. youngae, the most closely related species. Biochemical characteristics consolidated the fact that the two isolates represent a separate species, for which the name Citrobacter pasteurii sp. nov. is proposed. The type strain is CIP 55.13(T) ( =DSM 28879(T) =Na 1a(T)).

  14. Citrobacter koseri septicaemia in a holstein calf.

    PubMed

    Komine, M; Massa, A; Moon, L; Mullaney, T

    2014-11-01

    A 4-day-old male Holstein calf with dull mentation, nystagmus and blindness was humanely destroyed and subject to necropsy examination. Gross lesions included severe suppurative meningitis characterized by diffuse cloudy thickening of the meninges, bilateral hypopyon and fibrinosuppurative polyarthritis affecting the hocks. Citrobacter koseri was isolated from the meninges, ocular fluid, synovial fluid, spleen and small intestine. Microscopically, there was neutrophilic and histiocytic meningitis with intralesional bacilli, endophthalmitis, neutrophilic splenitis and multiple renal microabscesses. Failure of passive transfer of colostrum was confirmed. This appears to be the first characterization of septicaemia in a calf caused by C. koseri, with lesions comparable with those described in human neonates.

  15. Phenotypic detection and molecular characterization of beta-lactamase genes among Citrobacter species in a tertiary care hospital

    PubMed Central

    Praharaj, Ashok Kumar; Khajuria, Atul; Kumar, Mahadevan; Grover, Naveen

    2016-01-01

    Objective: To examine the distribution, emergence, and spread of genes encoding beta-lactamase resistance in Citrobacter species isolated from hospitalized patients in a tertiary care hospital. Methods: A prospective study was conducted in a 1000-bed tertiary care center in Pune, India from October 2010 to October 2013. A total of 221 Citrobacter spp. isolates were recovered from clinical specimens from different patients (one isolate per patient) admitted to the surgical ward, medical ward and medical and surgical Intensive Care Units. Polymerase chain reaction (PCR) assays and sequencing were used to determine the presence of beta-lactamase encoding genes. Conjugation experiments were performed to determine their transferability. Isolate relatedness were determined by repetitive element based-PCR, enterobacterial repetitive intergenic consensus-PCR and randomly amplified polymorphic DNA. Results: Among 221 tested isolates of Citrobacter spp. recovered from various clinical specimens, 179 (80.9%) isolates showed minimum inhibitory concentration (MIC) >4 μg/ml against meropenem and imipenem. One hundred and forty-five isolates with increased MICs value against carbapenems were further processed for molecular characterization of beta-lactamase genes. Susceptibility profiling of the isolates indicated that 100% retained susceptibility to colistin. Conjugation experiments indicated that blaNDM-1 was transferable via a plasmid. Conclusion: The ease of NDM-1 plasmid transmissibility may help their dissemination among the Citrobacter species as well as to others in Enterobacteriaceae. Early detection, antimicrobial stewardship and adequate infection control measures will help in limiting the spread of these organisms. PMID:26952135

  16. Citrobacter rodentium mouse model of bacterial infection.

    PubMed

    Crepin, Valerie F; Collins, James W; Habibzay, Maryam; Frankel, Gad

    2016-10-01

    Infection of mice with Citrobacter rodentium is a robust model to study bacterial pathogenesis, mucosal immunology, the health benefits of probiotics and the role of the microbiota during infection. C. rodentium was first isolated by Barthold from an outbreak of mouse diarrhea in Yale University in 1972 and was 'rediscovered' by Falkow and Schauer in 1993. Since then the use of the model has proliferated, and it is now the gold standard for studying virulence of the closely related human pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Here we provide a detailed protocol for various applications of the model, including bacterial growth, site-directed mutagenesis, mouse inoculation (from cultured cells and after cohabitation), monitoring of bacterial colonization, tissue extraction and analysis, immune responses, probiotic treatment and microbiota analysis. The main protocol, from mouse infection to clearance and analysis of tissues and host responses, takes ∼5 weeks to complete. PMID:27606775

  17. Musculoskeletal infections associated with Citrobacter koseri.

    PubMed

    Kwaees, T A; Hakim, Z; Weerasinghe, C; Dunkow, P

    2016-09-01

    Introduction Citrobacter koseri is a well known cause of central nervous system infections in the paediatric setting. Musculoskeletal infections caused by C koseri are rare, with only 14 previously reported cases. We present the first recorded case of C koseri induced septic arthritis of the knee along with a review of the literature. Methods A search of the PubMed, Embase(®) and Google Scholar™ databases was undertaken. Only complete or near complete cases were reviewed. Findings Fourteen musculoskeletal infections were identified. Of these, five were associated with an operative procedure and five involved a septic joint. Surgical treatment was required in the majority of cases and cure was achieved in all cases following prolonged antibiotic use. Conclusions C koseri associated musculoskeletal infections may complicate primary orthopaedic procedures. The organism can present aggressively and can be difficult to identify microbiologically. It is sensitive to newer generation beta-lactams, cephalosporin-based antibiotics and timely surgery. PMID:27412805

  18. Citrobacter koseri folliculitis of the face.

    PubMed

    Raia, D D; Barbareschi, M; Veraldi, S

    2015-10-01

    We report a case of severe Citrobacter koseri folliculitis of the face in a boy with acne. A 15-year-old boy affected by acne was admitted because of a rash located on the face. Dermatological examination revealed two large plaques, with numerous pustules, eschars and crusts, located bilaterally and symmetrically on the cheeks. Three bacteriological examinations were positive for C. koseri. The patient was successfully treated with i.m. ceftriaxone. C. koseri is a Gram-negative, aerobic, mobile, nonsporulating bacillus belonging to the Enterobacteriaceae family. It can cause meningitis, central nervous system abscess and sepsis, almost exclusively in infants and immunocompromised hosts. Respiratory tract and urinary infections have been reported in elderly people. Furthermore, rare cases of skin infections have been described.

  19. Musculoskeletal infections associated with Citrobacter koseri.

    PubMed

    Kwaees, T A; Hakim, Z; Weerasinghe, C; Dunkow, P

    2016-09-01

    Introduction Citrobacter koseri is a well known cause of central nervous system infections in the paediatric setting. Musculoskeletal infections caused by C koseri are rare, with only 14 previously reported cases. We present the first recorded case of C koseri induced septic arthritis of the knee along with a review of the literature. Methods A search of the PubMed, Embase(®) and Google Scholar™ databases was undertaken. Only complete or near complete cases were reviewed. Findings Fourteen musculoskeletal infections were identified. Of these, five were associated with an operative procedure and five involved a septic joint. Surgical treatment was required in the majority of cases and cure was achieved in all cases following prolonged antibiotic use. Conclusions C koseri associated musculoskeletal infections may complicate primary orthopaedic procedures. The organism can present aggressively and can be difficult to identify microbiologically. It is sensitive to newer generation beta-lactams, cephalosporin-based antibiotics and timely surgery.

  20. [Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria].

    PubMed

    Igari, Jun; Oguri, Toyoko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

    2002-02-01

    As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the bacteria were also evaluated with the bacterial resistance ratio calculated with the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of Moraxella (Branhamella) catarrhalis (n = 136), Haemophilus influenzae (n = 289), Escherichia coli (n = 276), Klebsiella pneumoniae (n = 192), Klebsiella oxytoca (n = 157), Enterobacter cloacae (n = 189), Enterobacter aerogenes (n = 93), Serratia marcescens (n = 172), Serratia liquefaciens (n = 24), Citrobacter freundii (n = 177), Citrobacter koseri (n = 70), Proteus mirabilis (n = 113), Proteus vulgaris (n = 89), Morganella morganii (n = 116), Providencia spp. (n = 41), Pseudomonas aeruginosa (n = 290), Pseudomonas fluorescens (n = 56), Pseudomonas putida (n = 63), Acinetobacter baumannii (n = 146), Acinetobacter lwoffii (n = 34), Burkholderia cepacia (n = 101), Stenotrophomonas maltophilia (n = 169), Bacteroides fragilis group (n = 196), and Prevotella/Porphyromonas (n = 173). An antibacterial activity of CZOP against E. coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with or more preferable than the study results obtained until the new drug application approval. MIC90 of CZOP against M.(B.) catarrhalis, C. koseri, and P. aeruginosa was not considerably changed and consistent with the study results obtained until the new drug application approval. MIC90 of CZOP against E. cloacae, E. aerogenes, and P. mirabilis increased year by year. The increase in MIC90 of CZOP against E. aerogenes and P. mirabilis, however, was not considered to be an obvious decline in susceptibility. In

  1. Clinical problems of sloths (Bradypus sp. and Choloepus sp.) in captivity.

    PubMed

    Diniz, L S; Oliveira, P M

    1999-03-01

    A 20-yr retrospective study of disease prevalence was carried out for 51 sloths (34 Bradypus sp. and 17 Choloepus sp.) at the São Paulo Zoo. A total of 81 clinical disorders were detected, including nutritional (45.7%), digestive (12.3%), and respiratory (12.3%) problems and injuries (6.1%). A definitive diagnosis was not possible in 8.6% of the cases. The incidence of disease varied according to seasonal climate (winter, 32.5%; spring, 24%; summer, 22.9%; autumn, 20.5%), time in captivity (96.4% of diseases occurred within the first 6 mo and 3.6% occurred thereafter), and type of enclosure (quarantine cage, 96.4%; exhibition enclosure, 3.6%). Both young animals (86.7%) and adults (3.2%) were affected. Parasites were identified by fecal examination in 45.4% of animals with clinical illness (Ascaris sp., 80%; Coccidia sp., 20%). Bacteria such as Salmonella enteritidis, Escherichia coli, and Citrobacter freundii were isolated from feces and/or organs. The first 6 mo in captivity are critical for these animals. Proper management and early identification of medical conditions in captivity have implications for sloth population in the wild.

  2. [Septic shock following platelet transfusion contaminated with Citrobacter koseri in a child with postchemotherapy febrile neutropenia].

    PubMed

    Tichit, R; Saumet, L; Marchandin, H; Haouy, S; Latry, P; Sirvent, N

    2016-01-01

    The bacterial transfusion risk is currently the greatest infectious risk of blood transfusion. We report the case of a child with postchemotherapy febrile neutropenia who presented septic shock following platelet transfusion contaminated with Citrobacter koseri. The life-threatening development could have been avoided by strict compliance with good clinical practice. The stability of mortality rates due to adverse effects of bacterial proliferation during platelet transfusions in France since 1994 calls for optimization of all preventive measures throughout the transfusion chain and perfect knowledge of transfusion rules by medical staff and care givers.

  3. In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, S-649266, against Enterobacteriaceae Clinical Isolates, Including Carbapenem-Resistant Strains.

    PubMed

    Kohira, Naoki; West, Joshua; Ito, Akinobu; Ito-Horiyama, Tsukasa; Nakamura, Rio; Sato, Takafumi; Rittenhouse, Stephen; Tsuji, Masakatsu; Yamano, Yoshinori

    2015-11-16

    S-649266 is a novel siderophore cephalosporin antibiotic with a catechol moiety on the 3-position side chain. Two sets of clinical isolate collections were used to evaluate the antimicrobial activity of S-649266 against Enterobacteriaceae. These sets included 617 global isolates collected between 2009 and 2011 and 233 β-lactamase-identified isolates, including 47 KPC-, 49 NDM-, 12 VIM-, and 8 IMP-producers. The MIC90 values of S-649266 against the first set of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Enterobacter aerogenes, and Enterobacter cloacae isolates were all ≤1 μg/ml, and there were only 8 isolates (1.3%) among these 617 clinical isolates with MIC values of ≥8 μg/ml. In the second set, the MIC values of S-649266 were ≤4 μg/ml against 109 strains among 116 KPC-producing and class B (metallo) carbapenemase-producing strains. In addition, S-649266 showed MIC values of ≤2 μg/ml against each of the 13 strains that produced other types of carbapenemases such as SME, NMC, and OXA-48. The mechanisms of the decreased susceptibility of 7 class B carbapenemase-producing strains with MIC values of ≥16 μg/ml are uncertain. This is the first report to demonstrate that S-649266, a novel siderophore cephalosporin, has significant antimicrobial activity against Enterobacteriaceae, including strains that produce carbapenemases such as KPC and NDM-1.

  4. 21 CFR 866.3125 - Citrobacter spp. serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Citrobacter spp. serological reagents. 866.3125 Section 866.3125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3125...

  5. 21 CFR 866.3125 - Citrobacter spp. serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Citrobacter spp. serological reagents. 866.3125 Section 866.3125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3125...

  6. 21 CFR 866.3125 - Citrobacter spp. serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Citrobacter spp. serological reagents. 866.3125 Section 866.3125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3125...

  7. 21 CFR 866.3125 - Citrobacter spp. serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Citrobacter spp. serological reagents. 866.3125 Section 866.3125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3125...

  8. 21 CFR 866.3125 - Citrobacter spp. serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Citrobacter spp. serological reagents. 866.3125 Section 866.3125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3125...

  9. Citrobacter amalonaticus human urinary tract infections, Marseille, France.

    PubMed

    Garcia, V; Abat, C; Moal, V; Rolain, J-M

    2016-05-01

    Citrobacter amalonaticus is a bacterium that has rarely been reported as a human pathogen. Here we report four cases of C. amalonaticus infections occurring in patients hospitalized in Marseille, France, and review all cases described in the published literature.

  10. Identification of Opportunistic Pathogenic Bacteria in Drinking Water Samples of Different Rural Health Centers and Their Clinical Impacts on Humans

    PubMed Central

    Pindi, Pavan Kumar; Raghuveer Yadav, P.; Shiva Shanker, A.

    2013-01-01

    International drinking water quality monitoring programs have been established in order to prevent or to reduce the risk of contracting water-related infections. A survey was performed on groundwater-derived drinking water from 13 different hospitals in the Mahabubnagar District. A total of 55 bacterial strains were isolated which belonged to both gram-positive and gram-negative bacteria. All the taxa were identified based on the 16S rRNA gene sequence analysis based on which they are phylogenetically close to 27 different taxa. Many of the strains are closely related to their phylogenetic neighbors and exhibit from 98.4 to 100% sequence similarity at the 16S rRNA gene sequence level. The most common group was similar to Acinetobacter junii (21.8%) and Acinetobacter calcoaceticus (10.9%) which were shared by 7 and 5 water samples, respectively. Out of 55 isolates, only 3 isolates belonged to coliform group which are Citrobacter freundii and Pantoea anthophila. More than half (52.7%, 29 strains) of the phylogenetic neighbors which belonged to 12 groups were reported to be pathogenic and isolated from clinical specimens. Out of 27 representative taxa are affiliated have eight representative genera in drinking water except for those affiliated with the genera Exiguobacterium, Delftia, Kocuria, and Lysinibacillus. PMID:23862144

  11. Citrobacter koseri: an unusual cause of pyogenic liver abscess

    PubMed Central

    Gupta, Monica; Sharma, Alka; Singh, Ram; Lehl, S S

    2013-01-01

    Liver abscess is a common pathology in the Indian subcontinent and usually results from amoebic or bacterial infection. Pyogenic abscesses usually occur in those with underlying predisposing factors like intra-abdominal infections, biliary infections or comorbidities like malignancy, immunosuppression, diabetes mellitus and previous biliary surgery or interventional endoscopy. Citrobacter is an unusual cause of pyogenic liver abscess and may occur in the setting of underlying comorbidities. We report a 56-year-old man with diabetes (operated for periampullary carcinoma 20 years ago), who presented with a history of fever for 1 week and on evaluation was found to have Citrobacter koseri-related hepatic abscess. The patient was managed with parenteral antibiotics, repeated aspiration of liver abscess and pigtail drainage. PMID:23505286

  12. Citrobacter koseri Pneumonia As Initial Presentation of Underlying Pulmonary Adenocarcinoma

    PubMed Central

    Pennington, Kelly; Van Zyl, Martin; Escalante, Patricio

    2016-01-01

    Citrobacter koseri is a motile, gram-negative rod traditionally known to cause infection in individuals with significant comorbidities and immunocompromised status. While most cases represent nosocomial infections, rarely community-acquired infections have been reported. We present a previously healthy man in his 60s with C. koseri pneumonia who was subsequently found to have underlying pulmonary adenocarcinoma, illustrating the need for further investigation for immunodeficiency and/or intrapulmonary pathology. PMID:27746678

  13. In vitro activity of ceftazidime, ceftaroline and aztreonam alone and in combination with avibactam against European Gram-negative and Gram-positive clinical isolates.

    PubMed

    Testa, Raymond; Cantón, Rafael; Giani, Tommaso; Morosini, María-Isabel; Nichols, Wright W; Seifert, Harald; Stefanik, Danuta; Rossolini, Gian Maria; Nordmann, Patrice

    2015-06-01

    Recent clinical isolates of key Gram-negative and Gram-positive bacteria were collected in 2012 from hospitalised patients in medical centres in four European countries (France, Germany, Italy and Spain) and were tested using standard broth microdilution methodology to assess the impact of 4 mg/L avibactam on the in vitro activities of ceftazidime, ceftaroline and aztreonam. Against Enterobacteriaceae, addition of avibactam significantly enhanced the level of activity of these antimicrobials. MIC(90) values (minimum inhibitory concentration that inhibits 90% of the isolates) of ceftazidime, ceftaroline and aztreonam for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii and Morganella morganii were reduced up to 128-fold or greater when combined with avibactam. A two-fold reduction in the MIC(90) of ceftazidime to 8 mg/L was noted in Pseudomonas aeruginosa isolates when combined with avibactam, whereas little effect of avibactam was noted on the MIC values of the test compounds when tested against Acinetobacter baumannii isolates. Avibactam had little effect on the excellent activity of ceftazidime, ceftaroline and aztreonam against Haemophilus influenzae. It had no impact on the in vitro activity of ceftazidime and ceftaroline against staphylococci and streptococci. This study demonstrates that addition of avibactam enhances the activities of ceftazidime, ceftaroline and aztreonam against Enterobacteriaceae and P. aeruginosa but not against A. baumannii.

  14. [Clinical and bacteriological characteristic of infectious purulent complications in patients after related renal transplantation].

    PubMed

    Volynchik, E P; Bol'shakov, L V; Bogomolova, N S; Kuznetsova, S M

    2014-01-01

    We investigated the frequency and characteristics of infectious purulent and non-infectious complications in living related renal transplant recipients in early postoperative period. It was identified the prevalent microorganisms in urinary tract infections and its antibiotic sensitivity: Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Staphylococcus epidermidis, Enterococcus faecalis, Candida albicans. 182 strains of bacteria and Candida were isolated from urine of renal graft patients in early postoperative period (from 2 days to 3 months). The prevention and treatment schemes, antimicrobial drugs dosing regimen were developed. It leads to decrease the infectious complications rate. PMID:25327674

  15. Genome sequence of Citrobacter sp. strain A1, a dye-degrading bacterium.

    PubMed

    Chan, Giek Far; Gan, Han Ming; Rashid, Noor Aini Abdul

    2012-10-01

    Citrobacter sp. strain A1, isolated from a sewage oxidation pond, is a facultative aerobe and mesophilic dye-degrading bacterium. This organism degrades azo dyes efficiently via azo reduction and desulfonation, followed by the successive biotransformation of dye intermediates under an aerobic environment. Here we report the draft genome sequence of Citrobacter sp. A1.

  16. Structural and serological studies on the O-antigen show that Citrobacter youngae PCM1505 must be classified to a new Citrobacter O-serogroup.

    PubMed

    Katzenellenbogen, Ewa; Kocharova, Nina A; Górska-Frączek, Sabina; Gamian, Andrzej; Shashkov, Alexander S; Knirel, Yuriy A

    2012-10-01

    The O-polysaccharide obtained by mild acid hydrolysis of the lipopolysaccharide of Citrobacter youngae PCM1505 was studied by sugar and methylation analyses along with 1D and 2D (1)H and (13)C NMR spectroscopies. The following structure of the tetrasaccharide repeating unit of the polysaccharide was established: [Formula: see text]. Structural and serological data obtained earlier and in this work show that the strain studied is a candidate to a new Citrobacter O-serogroup.

  17. In vitro activity of sparfloxacin (CI-978; AT-4140) against clinical isolates from cancer patients.

    PubMed Central

    Rolston, K V; Nguyen, H; Messer, M; LeBlanc, B; Ho, D H; Bodey, G P

    1990-01-01

    The in vitro activity of sparfloxacin, a new quinolone, was compared with those of ciprofloxacin and fleroxacin against gram-positive and gram-negative bacteria, greater than 90% of which were isolated from blood culture specimens of cancer patients. Sparfloxacin was extremely active against Acinetobacter species, Aeromonas hydrophila, Citrobacter diversus, Enterobacter species, Escherichia coli, Klebsiella species, Proteus vulgaris, and Serratia marcescens (inhibiting greater than 90% of these isolates at a concentration of 0.5 microgram/ml) and moderately active against Pseudomonas species, other Proteus species, and Citrobacter freundii. Sparfloxacin inhibited greater than 90% of staphylococci (including methicillin-resistant and coagulase-negative strains) at a concentration of 0.12 microgram/ml and greater than 90% of streptococci (including Streptococcus pneumoniae) at a concentration of 1.0 microgram/ml. It was also active against Bacillus cereus, Enterococcus species, and Corynebacterium jeikeium, organisms that have become fairly common in cancer patients. PMID:2127348

  18. Characterization of extended-spectrum β-lactamase (ESBL)-producing Klebsiella, Enterobacter, and Citrobacter obtained in environmental samples of a Tunisian hospital.

    PubMed

    Dziri, Raoudha; Klibi, Naouel; Alonso, Carla Andrea; Said, Leila Ben; Bellaaj, Ridha; Slama, Karim Ben; Boudabous, Abdellatif; Torres, Carmen

    2016-10-01

    The assessment of the hospital environment as a reservoir of ESBL-producing Enterobacteriaceae in Tunisian hospitals is scarcely analyzed, except for Escherichia coli. The aim of this study was to evaluate the presence of ESBL-producing non-E. coli Enterobacteriaceae (ESBL-EbNoEc) in 300 samples of abiotic surfaces and the hands of patients and staff of a Tunisian Hospital, and to characterize the ESBL genes of the recovered isolates. ESBL-EbNoEc were recovered in 28 of 300 (9.3%) analyzed samples and were identified as Klebsiella pneumoniae (n= 11), Enterobacter cloacae (n=11), Citrobacter freundii (n=4) and Klebsiella oxytoca (n=2). The bla genes identified by PCR and sequencing among the strains were as follows: 11 K.pneumoniae strains [blaCTX-M-15+ blaTEM-1+ blaSHV-11 (n=6); blaCTX-M-15+ blaTEM-1+ blaSHV-28 (n=3); blaCTX-M-15+ blaTEM-1+ blaSHV-1 (n=2)], 11 E. cloacae strains [blaCTX-M-15 (n=6); blaCTX-M-15+ blaTEM-1b (n=2); blaCTX-M-15+ blaTEM-1b+ blaOXA-1 (n=1);blaCTX-M-15+ blaOXA-1 (n=1);blaSHV-12 (n=1)], 4 C. freundii strains [blaCTX-M-15] and 2 K. oxytoca strains [blaCTX-M-15 (n=1); blaSHV-12 (n=1)]. The ISEcp1 and orf477 sequences were identified upstream and downstream of the blaCTX-M-15 gene, respectively, in 3 K. pneumoniae and 3 E. cloacae isolates. The PFGE analysis demonstrated three unrelated pulsotypes in K. pneumoniae strains and five pulsotypes in E. cloacae. The uncontrolled dissemination of ESBL-producing bacteria, even in the hospital environment, has become a real problem and new strategies and hygienic rules are needed to stop this bacterial dissemination. PMID:27492133

  19. Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration.

    PubMed

    Lopez, Christopher A; Miller, Brittany M; Rivera-Chávez, Fabian; Velazquez, Eric M; Byndloss, Mariana X; Chávez-Arroyo, Alfredo; Lokken, Kristen L; Tsolis, Renée M; Winter, Sebastian E; Bäumler, Andreas J

    2016-09-16

    Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonic crypt hyperplasia in mice, thereby gaining an edge during its competition with the gut microbiota through an unknown mechanism. Here, we show that by triggering colonic crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygenation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the γ-secretase inhibitor dibenzazepine to diminish Notch-driven colonic crypt hyperplasia curtailed the fitness advantage conferred by aerobic respiration during C. rodentium infection. We conclude that C. rodentium uses its T3SS to induce histopathological lesions that generate an intestinal microenvironment in which growth of the pathogen is fueled by aerobic respiration. PMID:27634526

  20. A generalized transducing phage for the murine pathogen Citrobacter rodentium

    PubMed Central

    Petty, Nicola K.; Toribio, Ana L.; Goulding, David; Foulds, Ian; Thomson, Nicholas; Dougan, Gordon; Salmond, George P. C.

    2008-01-01

    A virulent phage (φCR1) capable of generalized transduction in Citrobacter rodentium was isolated from the environment and characterized. C. rodentium is a natural pathogen of mice, causing transmissible murine colonic hyperplasia. Sequencing of its genome has recently been completed and will soon be fully annotated and published. C. rodentium is an important model organism for infections caused by the human pathogens enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC). φCR1 uses a lipopolysaccharide receptor, has a genome size of approximately 300 kb, and is able to transduce a variety of markers. φCR1 is the first reported transducing phage for C. rodentium and will be a useful tool for functional genomic analysis of this important natural murine pathogen. PMID:17768241

  1. Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002-2005.

    PubMed

    Cambau, E; Lascols, C; Sougakoff, W; Bébéar, C; Bonnet, R; Cavallo, J-D; Gutmann, L; Ploy, M-C; Jarlier, V; Soussy, C-J; Robert, J

    2006-10-01

    Bacteria harbouring the novel qnrA plasmid-mediated mechanism of quinolone resistance have been described in different countries, but the frequency of their occurrence has not been investigated. In total, 1,468 clinical isolates of Enterobacteriaceae with quinolone resistance or extended-spectrum beta-lactamase (ESBL) phenotypes were collected from eight teaching hospitals in France during 2002-2005 and screened for qnrA. Overall, 28 isolates (22 Enterobacter cloacae, three Klebsiella pneumoniae, one Citrobacter freundii, one Klebsiella oxytoca and one Proteus mirabilis) were positive for qnrA, representing 1.9% of all isolates, 3.3% of ESBL-producing isolates (22% of the E. cloacae isolates) and 0% of non-ESBL-producing isolates. The prevalence of qnrA among consecutive ESBL-producing isolates in 2004 from the eight hospitals was 2.8% (18/639). Of the qnrA-positive isolates, 100% were intermediately-resistant or resistant to nalidixic acid, and 75% to ciprofloxacin. Twenty-one of the 22 qnrA-positive E. cloacae isolates were obtained from two hospitals in the Paris area, and molecular typing and plasmid content analysis showed clonal relationships for five, three and two isolates, respectively. The qnrA genetic environment was similar to that of the In36 integron. The remaining two isolates had qnrA variants (30 and 29 nucleotide differences, respectively, compared with the original sequence) and an unknown genetic environment. The ESBL gene associated with qnrA was bla(SHV-12) in most of the isolates, but bla(PER-1) and bla(SHV-2a) were found in two isolates. In France, it appears that qnrA-positive isolates are predominantly E. cloacae isolates producing SHV-12, and may be associated with the dissemination of an In36-like integron. PMID:16961639

  2. In vitro antibacterial potency of Butea monosperma Lam. against 12 clinically isolated multidrug resistant bacteria

    PubMed Central

    Sahu, Mahesh Chandra; Padhy, Rabindra Nath

    2013-01-01

    Objective To investigate the antibacterial activity, using cold and hot extraction procedures with five solvents, petroleum ether, acetone, ethanol, methanol and water to validate medicinal uses of Butea monosperma Lam (B. monosperma) in controlling infections; and to qualitatively estimate phytochemical constituents of leaf-extracts of the plant. Methods The antibacterial activity of leaf-extracts was evaluated by the agar-well diffusion method against clinically isolated 12 Gram-positive and -negative multidrug resistant (MDR) pathogenic bacteria in vitro. Values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of leaf-extracts against each bacterium were obtained in a 96-well micro-titre plate, by broth dilution micro-titre plate technique. Results The presence of tannins, flavonoids, starch, glycosides and carbohydrates in different leaf extracts was established. Pathogenic bacteria used were, Acinetobacter sp., Chromobacterium violaceum, Citrobacter freundii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella sp., Enterococcus sp., Staphylococcus aureus (S. aureus), methicillin resistant S. aureus and vancomycin resistant S. aureus, along with standard bacterial strains. These MDR bacteria had been recorded to have significant inhibitions by leaf extracts, obtained by cold and hot extraction procedures with five solvents. In addition, the hot aqueous extract against Enterococcus sp. had the highest inhibition zone-size (21 mm). Ciprofloxacin 30 µg/disc was the positive/reference control and the diluting solvent, 10% dimethyl sulphoxide was the negative control. Recorded MIC values of different extracts ranged between 0.23 and 13.30 mg/mL, and MBC values were 0.52 to 30.00 mg/mL, for these bacteria. Conclusions Leaf-extracts with hot water and ethanol had shown significant antibacterial activity against all bacteria. B. monosperma leaf-extract could be used in treating infectious

  3. [Recovery of platinum with immobilized Citrobacter freudii XP05 biomass].

    PubMed

    Hu, Hong-Bo; Liu, Yue-Ying; Fu, Jin-Kun; Xue, Ru; Gu, Ping-Ying

    2003-07-01

    The objective of this work was to develop a valuable adsorbent for recovery of platinum by studying the properties of Pt4+ -adsorption with immobilized Citrobacter freudii XP05 biomass. Five methods for immobilization of Citrobacter freudii XP05 biomass were compared. The method with gelatin-alginate sodium as entrapment matrix was considered to be the optimal. Spherical and uniform beads were produced and the SEM micrograph indicated that the cell of strain XP08 were uniformly dispersed within the matrix. The adsorption of Pt4+ by immobilized XP05 biomass was affected with adsorptive time, pH value of the solution, immobilized biomass concentration, Pt4+ initial concentration The adsorption was a rapid process. The optimal pH value for Pt4+ adsorption was 1.5, and its adsorptive capacity increased linearly with increasing Pt4+ initial concentrations in the range of 50 - 250 mg/L. The experimental data could be fitted to Langmuir and Freundlich models of adsorption isotherm. The adsorptive capacity reached 35.2 mg/g under the conditions of 250 Pt4+ mg/L, 2.0 g/L immobilized biomass, pH 1.5 and 30 degrees C for 60 min. 98.7% of Pt4+ adsorbed on immobilized biomass could be desorbed with 0.5 mol HC1/L. The characteristics of dynamic adsorption and desorption of immobilized XP05 biomass in packed-bed reactor were investigated. The saturation uptake was 24.66 mg Pt4+ /g under the conditions of flow rate 1.2 mL/min, pH 1.5, 50 mg Pt4+/L and 1.85 g biomass(dry weight) . Adsorptive efficiency of Pt4 + by the immobilized XP05 biomass was above 78% for 4 cycles of adsorption and desorption. The recovery of platinum from waste platinum catalyst was studied. The adsorptive capacity was 20.94 mg Pt4+/g immobilized biomass under the conditions of 4.0 g/L immobilized XP05 biomass, 117.76 mg Pt4+/L and pH 1.5 for 60 min. The immobilized XP05 biomass is potentially applicable to the recovery of platinum from waste and wastewater containing platinum. PMID:15969064

  4. Virulence regulation in Citrobacter rodentium: the art of timing.

    PubMed

    Yang, Ji; Tauschek, Marija; Hart, Emily; Hartland, Elizabeth L; Robins-Browne, Roy M

    2010-05-01

    The mouse enteric pathogen Citrobacter rodentium, like its human counterpart, enteropathogenic Escherichia coli, causes attaching and effacing lesions in the intestinal epithelium of its host. This phenotype requires virulence factors encoded by the locus for enterocyte effacement (LEE) pathogenicity island. For timely expression of these virulence determinants at the site of infection and for efficient delivery of some virulence factors into epithelial cells, C. rodentium utilizes a positive regulatory loop involving the LEE-encoded regulatory proteins Ler, GrlA and GrlR to control LEE expression. Several transcription factors not encoded by LEE, some of which respond to specific environmental signals, also participate in this regulatory loop. Recently, we identified a non-LEE encoded, AraC-like regulatory protein, RegA, which plays a key role in the ability of C. rodentium to colonize the intestine. RegA functions by activating the transcription of a number of horizontally acquired operons encoding virulence-associated factors, such as autotransporters, fimbriae, a dispersin-like protein and its transporter. In addition, RegA represses transcription of a number of housekeeping genes. Importantly, RegA requires a gut-specific environmental signal, bicarbonate, to exert its effects on gene expression. In our proposed model, when C. rodentium senses bicarbonate ions in the gastrointestinal tract, RegA directs the bacterium to reduce the production of proteins involved in normal cellular functions, while enhancing the production of factors required for colonization and virulence.

  5. Fermented dairy products modulate Citrobacter rodentium-induced colonic hyperplasia.

    PubMed

    Collins, James W; Chervaux, Christian; Raymond, Benoit; Derrien, Muriel; Brazeilles, Rémi; Kosta, Artemis; Chambaud, Isabelle; Crepin, Valerie F; Frankel, Gad

    2014-10-01

    We evaluated the protective effects of fermented dairy products (FDPs) in an infection model, using the mouse pathogen Citrobacter rodentium (CR). Treatment of mice with FDP formulas A, B, and C or a control product did not affect CR colonization, organ specificity, or attaching and effacing lesion formation. Fermented dairy product A (FDP-A), but neither the supernatant from FDP-A nor β-irradiated (IR) FDP-A, caused a significant reduction in colonic crypt hyperplasia and CR-associated pathology. Profiling the gut microbiota revealed that IR-FDP-A promoted higher levels of phylotypes belonging to Alcaligenaceae and a decrease in Lachnospiraceae (Ruminococcus) during CR infection. Conversely, FDP-A prevented a decrease in Ruminococcus and increased Turicibacteraceae (Turicibacter). Importantly, loss of Ruminococcus and Turicibacter has been associated with susceptibility to dextran sodium sulfate-induced colitis. Our results demonstrate that viable bacteria in FDP-A reduced CR-induced colonic crypt hyperplasia and prevented the loss of key bacterial genera that may contribute to disease pathology.

  6. Favorable outcome in cerebral abscesses caused by Citrobacter koseri in a newborn infant.

    PubMed

    Algubaisi, Sarah; Bührer, Christoph; Thomale, Ulrich-Wilhelm; Spors, Birgit

    2015-01-01

    The treatment of brain abscesses in newborn infants is controversial. We report on a 6-week-old infant with multiple brain abscesses caused by Citrobacter koseri that resolved after treatment with combined surgical drainage and intravenous therapy with meropenem and fosfomycin.

  7. Complete genome sequence of novel carbon monoxide oxidizing bacteria Citrobacter amalonaticus Y19, assembled de novo.

    PubMed

    Ainala, Satish Kumar; Seol, Eunhee; Park, Sunghoon

    2015-10-10

    We report here the complete genome sequence of Citrobacter amalonaticus Y19 isolated from an anaerobic digester. PacBio single-molecule real-time (SMRT) sequencing was employed, resulting in a single scaffold of 5.58Mb. The sequence of a mega plasmid of 291Kb size is also presented.

  8. Understanding the host-adapted state of Citrobacter rodentium by transcriptomic analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrobacter rodentium (Cr) is a mouse pathogen that mimics many aspects of enteropathogenic Escherichia coli infections including producing attaching and effacing (A/E) lesions. Host-adapted (HA) Cr cells that are shed at the peak of infection have been reported to be hyperinfective. The exact mecha...

  9. Long-term selenium deficiency increases the pathogenicity of a Citrobacter rodentium infection in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrobacter rodentium is a mouse pathogen that causes infectious colitis and shares characteristics with human enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli, including the ability to cause attaching and effacing lesions in the colon, and serves as a useful model to study the ...

  10. Hypervirulent- host-associated Citrobacter rodentium cells have poor acid tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enhanced virulence or infectivity after passage through a mammalian host has been reported for a number of enteric food-borne pathogens. Citrobacter rodentium is a mouse pathogen that mimics many aspects of enterohemorrhagic E. coli infection of humans and serves as a useful model for studying viru...

  11. Phosphatase-mediated heavy metal accumulation by a Citrobacter sp. and related enterobacteria.

    PubMed

    Macaskie, L E; Bonthrone, K M; Rouch, D A

    1994-08-15

    A Citrobacter sp. was reported previously to accumulate heavy metals as cell-bound heavy metal phosphates. Metal uptake is mediated by the activity of a periplasmic acid-type phosphatase that liberates inorganic phosphate to provide the precipitant ligand for heavy metals presented to the cells. Amino acid sequencing of peptide fragments of the purified enzyme revealed significant homology to the phoN product (acid phosphatase) of some other enterobacteria. These organisms, together with Klebsiella pneumoniae, previously reported to produce acid phosphatase, were tested for their ability to remove uranium and lanthanum from challenge solutions supplemented with phosphatase substrate. The coupling of phosphate liberation to metal bioaccumulation was limited to the metal accumulating Citrobacter sp.; therefore the participation of species-specific additional factors in metal bioaccumulation was suggested.

  12. Development of a real-time PCR assay for quantification of Citrobacter rodentium.

    PubMed

    Sagaidak, Sofia; Taibi, Amel; Wen, Bijun; Comelli, Elena M

    2016-07-01

    Molecular tools to quantify Citrobacter rodentium are not available. We developed a quantitative PCR assay targeting the espB gene. This assay is specific, has a linearity range of about 6.7×10(1) to 6.7×10(6)cells/PCR reaction (92% efficiency) and a detection limit of about 10(4)cells/g wet feces.

  13. [Antimicrobial activity of tebipenem against various clinical isolates from various specimen, mainly urinary tract].

    PubMed

    Muratani, Tetsuro; Doi, Kazutake; Kobayashi, Tomoko; Nakamura, Tamaki; Matsumoto, Tetsuro

    2009-04-01

    Tebipenem is the active metabolite of ME1211, tebipenem pivoxil, a novel oral carbapenem that possesses potent activity against almost pathogens except for Pseudomonas aeruginosa. In this study, we compared the susceptibility of tebipenem with current antibiotics against various organisms isolated from various specimen, mainly urinary tract. Tebipenem had a potent activity against Neisseria gonorrhoeae; its activity was comparable to it of cefixime that has most potent activity among oral antibiotics. Against Enterococcus faecalis, the activity of tebipenem was comparable to the activities of ampicillin and amoxicillin, and superior to it of faropenem. Against Citrobacter freundii, Escherichia coli , Klebsiella pneumoniae, and Enterobacter spp. including extended-spectrum beta-lactamase producers, tebipenem had a potent activity with or without ceftazidime-resistance. PMID:19673353

  14. 1,3-propanediol production with Citrobacter werkmanii DSM17579: effect of a dhaD knock-out

    PubMed Central

    2014-01-01

    Background 1,3-propanediol (PDO) is a substantially industrial metabolite used in the polymer industry. Although several natural PDO production hosts exist, e.g. Klebsiella sp., Citrobacter sp. and Clostridium sp., the PDO yield on glycerol is insufficient for an economically viable bio-process. Enhancing this yield via strain improvement can be achieved by disconnecting the production and growth pathways. In the case of PDO formation, this approach results in a microorganism metabolizing glycerol strictly for PDO production, while catabolizing a co-substrate for growth and maintenance. We applied this strategy to improve the PDO production with Citrobacter werkmanii DSM17579. Results Genetic tools were developed and used to create Citrobacter werkmanii DSM17579 ∆dhaD in which dhaD, encoding for glycerol dehydrogenase, was deleted. Since this strain was unable to grow on glycerol anaerobically, both pathways were disconnected. The knock-out strain was perturbed with 13 different co-substrates for growth and maintenance. Glucose was the most promising, although a competition between NADH-consuming enzymes and 1,3-propanediol dehydrogenase emerged. Conclusion Due to the deletion of dhaD in Citrobacter werkmanii DSM17579, the PDO production and growth pathway were split. As a consequence, the PDO yield on glycerol was improved 1,5 times, strengthening the idea that Citrobacter werkmanii DSM17579 could become an industrially interesting host for PDO production. PMID:24885849

  15. Diversity of carbapenemases in clinical isolates of Enterobacteriaceae in Croatia--the results of a multicentre study.

    PubMed

    Zujić Atalić, V; Bedenić, B; Kocsis, E; Mazzariol, A; Sardelić, S; Barišić, M; Plečko, V; Bošnjak, Z; Mijač, M; Jajić, I; Vranić-Ladavac, M; Cornaglia, G

    2014-11-01

    Since the first carbapenem-resistant Klebsiella pneumoniae strain was isolated in 2008, Enterobacteriaceae with reduced susceptibility to one or more carbapenems have emerged sporadically in different geographical regions in Croatia. These observations gave rise to a multicenter study on carbapenem resistance in Enterobacteriaceae from Croatia. Fifty-seven carbapenem-non-susceptible strains of Enterobacteriaceae were collected during 2011-2012 from four large hospital centres in Croatia. Overall, 36 strains produced VIM-1 β-lactamase, three produced NDM-1, and one produced KPC-2. A high degree of clonal relatedness was observed in Enterobacter cloacae and Citrobacter freundii strains, in contrast to K. pneumoniae strains. BlaVIM genes were located within class1 integron which contained genes encoding resistance to aminoglycosides (aacA4 ). The study found strong association between blaVIM and qnrB6 and between blaNDM and qnrA6 genes.

  16. Microbiological quality of ready-to-eat salads: an underestimated vehicle of bacteria and clinically relevant antibiotic resistance genes.

    PubMed

    Campos, Joana; Mourão, Joana; Pestana, Nazaré; Peixe, Luísa; Novais, Carla; Antunes, Patrícia

    2013-09-16

    terrigena carrying a bla(SHV-2) and 1 Citrobacter freundii isolate with a qnrB9 gene. Among Enterococcus (n=108; 35 samples; Enterococcus casseliflavus--40, Enterococcus faecalis--20, Enterococcus faecium--18, Enterococcus hirae--9, Enterococcus gallinarum--5, and Enterococcus spp.--16) resistance was detected for tetracyclines [6%; tet(M) and/or tet(L)], erythromycin [3%; erm(B)], nitrofurantoin (1%) or ciprofloxacin (1%). The present study places ready-to-eat salads within the spectrum of ecological niches that may be vehicles for antibiotic resistance bacteria/genes with clinical interest (e.g. E. coli-D-ST69; bla(SHV-2)) and these findings are worthy of attention as their spread to humans by ingestion cannot be dismissed.

  17. Dietary Chitosan Supplementation Increases Microbial Diversity and Attenuates the Severity of Citrobacter rodentium Infection in Mice

    PubMed Central

    Wang, Hongbing; Xiong, Xia; Tan, Bie; Al-Dhabi, Naif Abdullah; Fang, Jun

    2016-01-01

    C57BL/6 mice were tested in order to investigate the effects of dietary chitosan (COS) supplements on intestinal microflora and resistance to Citrobacter rodentium infection. The findings reveal that, after consuming a 300 mg/kg COS diet for 14 days, microflora became more diverse as a result of the supplement. Mice receiving COS exhibited an increase in the percentage of Bacteroidetes phylum and a decrease in the percentage of Firmicutes phylum. After Citrobacter rodentium infection, the histopathology scores indicated that COS feeding resulted in less severe colitis. IL-6 and TNF-α were significantly lower in colon from COS-feeding mice than those in the control group. Furthermore, mice in COS group were also found to experience inhibited activation of nuclear factor-kappa B (NF-κB) in the colonic tissue. Overall, the findings revealed that adding 300 mg/kg COS to the diet changed the composition of the intestinal microflora of mice, resulting in suppressed NF-κB activation and less production of TNF-α and IL-6; and these changes led to better control of inflammation and resolution of infection with C. rodentium. PMID:27761062

  18. Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque

    PubMed Central

    Goh, Share-Yuan; Khan, Saad Ahmed; Tee, Kok Keng; Abu Kasim, Noor Hayaty; Yin, Wai-Fong; Chan, Kok-Gan

    2016-01-01

    Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium. PMID:26860259

  19. Selective enrichment of commensal gut bacteria protects against Citrobacter rodentium-induced colitis.

    PubMed

    Vong, Linda; Pinnell, Lee J; Määttänen, Pekka; Yeung, C William; Lurz, Eberhard; Sherman, Philip M

    2015-08-01

    The intestinal microbiota plays a key role in shaping the host immune system. Perturbation of gut microbial composition, termed dysbiosis, is associated with an increased susceptibility to intestinal pathogens and is a hallmark of a number of inflammatory, metabolic, and infectious diseases. The prospect of mining the commensal gut microbiota for bacterial strains that can impact immune function represents an attractive strategy to counteract dysbiosis and resulting disease. In this study, we show that selective enrichment of commensal gut lactobacilli protects against the murine pathogen Citrobacter rodentium, a well-characterized model of enteropathogenic and enterohemorrhagic Escherichia coli infection. The lactobacilli-enriched bacterial culture prevented the expansion of Gammaproteobacteria and Actinobacteria and was associated with improved indexes of epithelial barrier function (dextran flux), transmissible crypt hyperplasia, and tissue inflammatory cytokine levels. Moreover, cultivation of gut bacteria from Citrobacter rodentium-infected mice reveals the differential capacity of bacterial subsets to mobilize neutrophil oxidative burst and initiate the formation of weblike neutrophil extracellular traps. Our findings highlight the beneficial effects of a lactobacilli-enriched commensal gut microenvironment and, in the context of an intestinal barrier breach, the ability of neutrophils to immobilize both commensal and pathogenic bacteria.

  20. The pathogenicity of an enteric Citrobacter rodentium infection is enhanced by deficiencies in the antioxidants selenium and vitamin E

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrobacter rodentium is a mouse pathogen that shares many characteristics with human enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli, the causative agents for human disease, and serves as a useful model to study immunity to these organisms. In this study, the effect of a doub...

  1. Decolorization of textile plant effluent by Citrobacter sp. strain KCTC 18061P.

    PubMed

    Jang, Moon-Sun; Jung, Byung-Gil; Sung, Nak-Chang; Lee, Young-Choon

    2007-12-01

    Citrobacter sp. strain KCTC 18061P was found to be able to decolorize textile plant effluent containing different types of reactive dyes. Effects of physico-chemical parameters, such as aeration, nitrogen source, glucose and effluent concentrations on the color removal of real dye effluent by this strain were investigated. The observed changes in the visible spectra indicated color removal by the absorption of dye to cells during incubation with the strain. This strain showed higher decolorization ability under aerobic than static culture conditions. With 1% glucose, this strain removed 70% of effluent color within 5 days. Decolorization was not significantly dependent on the nitrogen sources tested. Chemical oxygen demand (COD) and biological oxygen demand (BOD) were decreased in proportion to incubation times, and their removal rates were about 35% and 50%, respectively, at 7 days of culture.

  2. Expression of intimin gamma from enterohemorrhagic Escherichia coli in Citrobacter rodentium.

    PubMed

    Hartland, E L; Huter, V; Higgins, L M; Goncalves, N S; Dougan, G; Phillips, A D; MacDonald, T T; Frankel, G

    2000-08-01

    The carboxy-terminal 280 amino acids (Int280) of the bacterial adhesion molecule intimin include the receptor-binding domain. At least five different types of Int280, designated alpha, beta, gamma, delta, and epsilon, have been described based on sequence variation in this region. Importantly, the intimin types are associated with different evolutionary branches and contribute to distinct tissue tropism of intimin-positive bacterial pathogens. In this study we engineered a strain of Citrobacter rodentium, which normally displays intimin beta, to express intimin gamma from enterohemorrhagic Escherichia coli. We show that intimin gamma binds to the translocated intimin receptor (Tir) from C. rodentium and has the ability to produce attaching and effacing lesions on HEp-2 cells. However, C. rodentium expressing intimin gamma could not colonize orally infected mice or induce mouse colonic hyperplasia. These results suggest that intimin may contribute to host specificity, possibly through its interaction with a receptor on the host cell surface.

  3. Citrobacter rodentium-induced colitis: A robust model to study mucosal immune responses in the gut.

    PubMed

    Koroleva, Ekaterina P; Halperin, Sydney; Gubernatorova, Ekaterina O; Macho-Fernandez, Elise; Spencer, Cody M; Tumanov, Alexei V

    2015-06-01

    Citrobacter rodentium is a natural mouse pathogen which reproducibly infects mice and causes intestinal disease. The C. rodentium model of infection is very useful for investigating host-pathogen immune interactions in the gut, and can also be used to understand the pathogenesis of several important human intestinal disorders, including Crohn's disease, ulcerative colitis, dysbiosis and colon tumorigenesis. Both innate and adaptive immune responses play a critical role in protection against C. rodentium. Here, we summarize the role of immune components in protection against C. rodentium and describe techniques for the analysis of innate and adaptive mucosal immune responses, including setting up the infection, analysis of colonic hyperplasia and bacterial dissemination, evaluation of antibody responses, and purification and analysis of intestinal epithelial and lymphoid cells.

  4. Evaluation of the in vitro activity of six broad-spectrum beta-lactam antimicrobial agents tested against over 2,000 clinical isolates from 22 medical centers in Japan. Japan Antimicrobial Resistance Study Group.

    PubMed

    Yamaguchi, K; Mathai, D; Biedenbach, D J; Lewis, M T; Gales, A C; Jones, R N

    1999-06-01

    Numerous broad-spectrum beta-lactam antimicrobial agents have been introduced into medical practice since 1985. Although several of these compounds have advanced, infectious disease therapy resistances to them has also emerged world-wide. In 1997, a Japanese 22 medical center investigation was initiated to assess the continued utility of these agents (oxacillin or piperacillin, ceftazidime, cefepime, cefpirome, cefoperazone/sulbactam [C/S], imipenem). The participating medical centers represented a wide geographic distribution, and a common protocol and reagents were applied. Three control strains and a set of challenge organisms were provided to participant centers. Etest (AB BIODISK, Solna, Sweden) strips were used in concurrent tests of these organisms and a qualitative determination of participant skills in the identification of resistant and susceptible phenotypes was established. The quantitative controls demonstrated 97.7-99.2% of MIC values within established QC limits, and the qualitative (susceptibility category) controls documented a 97.3% agreement of participant results with that of reference values (1,320 total results). Only 0.2% of values were false-susceptible errors. After the participant quality was assured, a total of 2,015 clinical strains were tested (10 strains from 10 different organism groups including methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci [CoNS], Escherichia coli, Klebsiella spp., Citrobacter freundii, Enterobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., and Pseudomonas aeruginosa). The staphylococci were uniformly susceptible to all drugs tested except ceftazidime (MIC90, 24 micrograms/ml) that had a potency six- to 12-fold less than either cefepime or cefpirome. Only 3.7 and 45.1% of S. aureus and CoNS were susceptible to ceftazidime, respectively. Among E. coli and Klebsiella spp. the rank order of antimicrobial spectrum was imipenem = "fourth

  5. O2-stable membrane-bound [NiFe]hydrogenase from a newly isolated Citrobacter sp. S-77.

    PubMed

    Eguchi, Shigenobu; Yoon, Ki-Seok; Ogo, Seiji

    2012-11-01

    Hydrogenases are of great interest due to their potential use in H(2)-based technology. However, most hydrogenases are highly sensitive to O(2), which have been the major bottleneck in hydrogenase studies. Here we report an O(2)-stable membrane-bound [NiFe]hydrogenase (MBH) purified from a newly isolated strain, S-77. According to the 16S rRNA gene sequence and phylogenetic analysis of the strain S-77, it belongs to the genus of Citrobacter. In vitro experiments using the cytoplasmic membrane of strain S-77 suggested that a cytochrome b acts as the physiological electron acceptor of the MBH. The purified MBH was composed of a dimer of heterodimers, consisting of two distinct subunits with the molecular weights of 58.5 and 38.5 kDa. The enzyme showed a specific activity for H(2)-oxidation of 661 U/mg, which is 35-fold greater than that for H(2)-production of 18.7 U/mg. Notably, the MBH showed a remarkable O(2)-stability, maintaining almost 95% of its original activity even after incubation for 30 h in air at 4°C. These results suggest that the O(2)-stable MBH may play an important role in the H(2)-metabolic pathway under the aerobic conditions of Citrobacter sp. S-77. This is the first report of the purification and biochemical characterization of an O(2)-stable MBH from the genus of Citrobacter.

  6. Identification, cloning and heterologous expression of active [NiFe]-hydrogenase 2 from Citrobacter sp. SG in Escherichia coli.

    PubMed

    Maier, Johannes A H; Ragozin, Sergey; Jeltsch, Albert

    2015-04-10

    Hydrogen (H2) is a potential alternative energy carrier which only produces water and heat upon combustion. Today, industrial hydrogen production mainly uses thermochemical processes based on fossil fuels or electrolysis of water. Therefore, biotechnological approaches to produce H2 from biomass are an interesting alternative. We introduce here a novel direct hydrogen measurement system using a semiconducting device specific for hydrogen detection. Using this device, a bacterium producing considerable amounts of hydrogen under aerobic cultivation was isolated and identified by 16S ribosomal DNA sequencing as Citrobacter sp. The enzyme responsible for the observed hydrogenase activity was partially purified by 3 chromatographic purification steps and could be identified by peptide mass fingerprinting to be a type 2 [NiFe]-hydrogenase. Expression of the [NiFe]-hydrogenase 2 containing operon from Citrobacter sp. SG in Escherichia coli allowed recombinant hydrogen production. The [NiFe]-hydrogenase 2 identified here may be useful for biotechnological hydrogen production. We speculate that the expression of the hydrogenase in Citrobacter may be an adaptation to growth in acidic conditions.

  7. Proteome responses of Citrobacter werkmanii BF-6 planktonic cells and biofilms to calcium chloride.

    PubMed

    Zhou, Gang; Shi, Qing-shan; Huang, Xiao-mo; Xie, Xiao-bao

    2016-02-01

    Calcium ions are well-known as intracellular second messengers that also have an important extracellular structural role for bacteria. Recently, we found that denser biofilms were formed by Citrobacter werkmanii BF-6 in the presence of 400 mM Ca(2+) than that of 12.5mM Ca(2+). Therefore, we employed two-dimensional (2-D) electrophoresis methods to investigate the proteome profiles of planktonic cells and biofilms in BF-6 under different concentrations of Ca(2+). Meanwhile, BF-6 biofilm architecture was also visualized with confocal laser scanning microscopy (CLSM). The results demonstrated that BF-6 biofilms formed at the bottom of microtiter plates when grown in the presence of 400 mM Ca(2+). A total of 151 proteins from planktonic cells and biofilms after exposure of BF-6 cells to 12.5 and 400 mM Ca(2+) were successfully identified. Different gene ontology (GO) and KEGG pathways were categorized and enriched for the above proteins. Growth in the presence of 400 mM Ca(2+) induced more complex signal pathways in BF-6 than 12.5mM Ca(2+). In addition, the biofilm architectures were also affected by Ca(2+). Our results show two different modes of biofilm enhancement for C. werkmanii in the presence of excess Ca(2+) and provide a preliminary expression of these differences based on proteomic assays.

  8. Psidium guajava leaf extract prevents intestinal colonization of Citrobacter rodentium in the mouse model.

    PubMed

    Gupta, Pooja; Birdi, Tannaz

    2015-01-01

    Diarrheal diseases are the second highest cause of mortality of children under 5 years worldwide. There is a continuous search for developing a cost-effective treatment for diarrhea as the present ones are facing challenges. Medicinal plants can be explored further as an alternative treatment for diarrhea. Psidium guajava leaves have been used as an antidiarrheal globally. Citrobacter rodentium, a common mouse pathogen, is known to mimic the pathogenecity of enteropathogenic and enterohemorrhagic E. coli. It can thus present an effective model to study infectious diarrhea. In the present study, the P. guajava leaf extract was tested for its efficacy in treating infectious diarrhea using a C. rodentium mouse model. The mice in the test group (treated with P. guajava leaf extract) showed quicker clearance of infection as compared with the control group. The bacterial load in the fecal sample of the mice in the test group was high on Day 4 as compared with that in the control group, suggesting a flush out of the bacteria. In the test group, 6/7 (85.71%) mice showed clearance of infection by Day 19. The control group continued to show infection till Day 29. P. guajava leaf extract thus has the potential for use in the treatment of infectious diarrhea. PMID:25878465

  9. DOCK2 confers immunity and intestinal colonization resistance to Citrobacter rodentium infection

    PubMed Central

    Liu, Zhiping; Man, Si Ming; Zhu, Qifan; Vogel, Peter; Frase, Sharon; Fukui, Yoshinori; Kanneganti, Thirumala-Devi

    2016-01-01

    Food poisoning is one of the leading causes of morbidity and mortality in the world. Citrobacter rodentium is an enteric pathogen which attaches itself to enterocytes and induces attachment and effacing (A/E) lesions. The ability of the bacterium to cause infection requires subversion of the host actin cytoskeleton. Rac-dependent actin polymerization is activated by a guanine nucleotide exchange factor known as Dedicator of cytokinesis 2 (DOCK2). However, the role of DOCK2 in infectious disease is largely unexplored. Here, we found that mice lacking DOCK2 were susceptible to C. rodentium infection. These mice harbored increased levels of C. rodentium bacteria, showed more pronounced weight loss and inflammation-associated pathology, and were prone to bacterial dissemination to the systemic organs compared with wild-type mice. We found that mice lacking DOCK2 were more susceptible to C. rodentium attachment to intestinal epithelial cells. Therefore, our results underscored an important role of DOCK2 for gastrointestinal immunity to C. rodentium infection. PMID:27291827

  10. Pathophysiology of Citrobacter diversus neonatal meningitis: comparative studies in an infant mouse model.

    PubMed Central

    Soriano, A L; Russell, R G; Johnson, D; Lagos, R; Sechter, I; Morris, J G

    1991-01-01

    Citrobacter diversus is a cause of devastating neonatal meningitis, with illness characterized by formation of multiple brain abscesses. We developed an infant mouse intracranial inoculation model to evaluate the pathophysiology of C. diversus neonatal infections. Eighteen of 26 strains inoculated intracranially at a dose of ca. 3.3 x 10(3) CFU caused greater than 50% mortality in 2-day-old mice. No correlation was seen between the epidemiologic characteristics of a strain and its rate of mortality. When seven C. diversus isolates (four isolates from patients with meningitis, three from non-central nervous system [CNS] sites) were further evaluated, mortality was significantly correlated with bacteremia. The initial lesion in the CNS was a suppurative ventriculitis beginning 1 to 2 days postinoculation. Subsequent ventriculomegaly was associated with ventriculitis and periventricular abscessation. Brain lesions were seen with all strains, although strains of low virulence (as measured by having no bacteremia and low mortality) caused less-severe damage. An age-related susceptibility to C. diversus brain lesions was demonstrated, with 5-day-old mice showing a significant reduction in, and 8-day-old mice being apparently resistant to, infection and CNS damage. Our data indicate that C. diversus has a propensity to cause abscess formation in the neonatal mouse brain, with characteristic pathologic findings; however, the factors that determine whether a strain will cause meningitis in a human infant remain to be identified. Images PMID:2004815

  11. Citrobacter rodentium espB Is Necessary for Signal Transduction and for Infection of Laboratory Mice

    PubMed Central

    Newman, Joseph V.; Zabel, Brian A.; Jha, Sharda S.; Schauer, David B.

    1999-01-01

    Citrobacter rodentium is the causative agent of transmissible murine colonic hyperplasia and contains a locus of enterocyte effacement (LEE) similar to that found in enteropathogenic Escherichia coli (EPEC). EPEC espB is necessary for intimate attachment and signal transduction between EPEC and cultured cell monolayers. Mice challenged with wild-type C. rodentium develop a mucosal immunoglobulin A response to EspB. In this study, C. rodentium espB has been cloned and its nucleotide sequence has been determined. C. rodentium espB was found to have 90% identity to EPEC espB. A nonpolar insertion mutation in C. rodentium espB was constructed and used to replace the chromosomal wild-type allele. The C. rodentium espB mutant exhibited reduced cell association and had no detectable fluorescent actin staining activity on cultured cell monolayers. The C. rodentium espB mutant also failed to colonize laboratory mice following experimental inoculation. The espB mutation could be complemented with a plasmid-encoded copy of the gene, which restored both cell association and fluorescent actin staining activity, as well as the ability to colonize laboratory mice. These studies indicate that espB is necessary for signal transduction and for colonization of laboratory mice by C. rodentium. PMID:10531262

  12. mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium

    PubMed Central

    Lin, Xingguang; Yang, Jialong; Wang, Jinli; Huang, Hongxiang; Wang, Hong-Xia; Chen, Pengcheng; Wang, Shang; Pan, Yun; Qiu, Yu-Rong; Taylor, Gregory A.; Vallance, Bruce A.; Gao, Jimin; Zhong, Xiao-Ping

    2016-01-01

    T-cells play an important role in promoting mucosal immunity against pathogens, but the mechanistic basis for their homeostasis in the intestine is still poorly understood. We report here that T-cell-specific deletion of mTOR results in dramatically decreased CD4 and CD8 T-cell numbers in the lamina propria of both small and large intestines under both steady-state and inflammatory conditions. These defects result in defective host resistance against a murine enteropathogen, Citrobacter rodentium, leading to the death of the animals. We further demonstrated that mTOR deficiency reduces the generation of gut-homing effector T-cells in both mesenteric lymph nodes and Peyer’s patches without obviously affecting expression of gut-homing molecules on those effector T-cells. Using mice with T-cell-specific ablation of Raptor/mTORC1 or Rictor/mTORC2, we revealed that both mTORC1 and, to a lesser extent, mTORC2 contribute to both CD4 and CD8 T-cell accumulation in the gastrointestinal (GI) tract. Additionally, mTORC1 but not mTORC2 plays an important role regulating the proliferative renewal of both CD4 and CD8 T-cells in the intestines. Our data thus reveal that mTOR is crucial for T-cell accumulation in the GI tract and for establishing local adaptive immunity against pathogens. PMID:27731345

  13. The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis.

    PubMed

    van Driel, Boaz; Wang, Guoxing; Liao, Gongxian; Halibozek, Peter J; Keszei, Marton; O'Keeffe, Michael S; Bhan, Atul K; Wang, Ninghai; Terhorst, Cox

    2015-09-01

    The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria. Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate responses to bacteria and regulates peripheral inflammation by assessing the outcome of C. rodentium infections in Rag(-/-) mice. Surprisingly, the pathology and immune responses in the lamina propria of C. rodentium-infected Slamf6(-/-) Rag(-/-) mice were markedly reduced as compared with those of Rag(-/-) mice. Infiltration of inflammatory phagocytes into the lamina propria was consistently lower in Slamf6(-/-) Rag(-/-) mice than in Rag(-/-) animals. Concomitant with the reduced systemic translocation of the bacteria was an enhanced production of IL-22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore, administering a mAb (330) that inhibits bacterial interactions with Slamf6 to Rag(-/-) mice ameliorated the infection compared with a control antibody. We conclude that Slamf6-mediated interactions of colonic innate immune cells with specific Gram(-) bacteria reduce mucosal protection and enhance inflammation, contributing to lethal colitis that is caused by C. rodentium infections in Rag(-/-) mice.

  14. Glycerol assimilation and production of 1,3-propanediol by Citrobacter amalonaticus Y19.

    PubMed

    Ainala, Satish Kumar; Ashok, Somasundar; Ko, Yeounjoo; Park, Sunghoon

    2013-06-01

    Citrobacter amalonaticus Y19 (Y19) was isolated because of its ability for carbon monoxide-dependent hydrogen production (water-gas shift reaction). This paper reports the assimilation of glycerol and the production of 1,3-propanediol (1,3-PDO) by Y19. Genome sequencing revealed that Y19 contained the genes for the utilization of glycerol and 1,2-propanediol (pdu operon) along with those for the synthesis of coenzyme B12 (cob operon). On the other hand, it did not possess the genes for the fermentative metabolism of glycerol of Klebsiella pneumoniae, which consists of both the oxidative (dhaD and dhaK) and reductive (dhaB and dhaT) pathways. In shake-flask cultivation under aerobic conditions, Y19 could grow well with glycerol as the sole carbon source and produced 1,3-PDO. The level of 1,3-PDO production was improved when vitamin B12 was added to the culture medium under aerobic conditions. Under anaerobic conditions, cell growth and 1,3-PDO production on glycerol was also possible, but only when an exogenous electron acceptor, such as nitrate or fumarate, was added. This is the first report of the glycerol metabolism and 1,3-PDO production by C. amalonaticus Y19.

  15. Understanding the host-adapted state of Citrobacter rodentium by transcriptomic analysis.

    PubMed

    Smith, Allen D; Yan, Xianghe; Chen, Celine; Dawson, Harry D; Bhagwat, Arvind A

    2016-05-01

    Citrobacter rodentium (Cr) is a mouse pathogen that mimics many aspects of enteropathogenic Escherichia coli infections including producing attaching and effacing (A/E) lesions. Host-adapted (HA) Cr cells that are shed at the peak of infection have been reported to be hyper-infective. The exact mechanism underlying this phenomenon has remained elusive since the pathogen loses its HA 'status' immediately upon subculturing in laboratory media. We sequenced the entire transcriptome of Cr directly from the feces of infected mice and analyzed the gene expression pattern. We observed that the entire transcriptional machinery as well as several transcriptional regulators to be differentially expressed when compared with the transcriptome of cells grown on laboratory media. Major adhesion and effector genes, tir and eae, were highly expressed in HA along with many genes located on all five loci of enterocyte effacement regions (LEE 1-5). Notable absent among the HA expressed genes were 19 fimbrial operons and non-fimbrial adhesions and several non-LEE encoded effectors. These results demonstrate that host-adapted Cr has a unique transcriptome that is associated with increased host transmission.

  16. Effect of surfactant on phenanthrene metabolic kinetics by Citrobacter sp. SA01.

    PubMed

    Li, Feng; Zhu, Lizhong; Zhang, Dong

    2014-11-01

    To attain a better understanding of the effects of surfactants on the metabolic kinetics of hydrophobic organic compounds, the biodegradation of phenanthrene by Citrobacter sp. SA01 was investigated in a batch experiment containing Tween 80, sodium dodecyl benzene sulfonate and liquid mineral salt medium. The Monod model was modified to effectively describe the partition, phenanthrene biodegradation and biopolymer production. The results showed that Tween 80 and sodium dodecyl benzene sulfonate (each at 50mg/L) enhanced phenanthrene metabolism and poly-β-hydroxybutyrate production as indicated by the increasing amounts of intermediates (by 17.2% to 47.9%), and percentages of poly-β-hydroxybutyrate (by 107.3% and 33.1%) within the cell dry weight when compared to their absence. The modified Monod model was capable of predicting microbial growth, phenanthrene depletion and biopolymer production. Furthermore, the Monod kinetic coefficients were largely determined by the surfactant-enhanced partition, suggesting that partitioning is a critical process in surfactant-enhanced bioremediation of hydrophobic organic compounds.

  17. Immunological mechanisms involved in probiotic-mediated protection against Citrobacter rodentium-induced colitis.

    PubMed

    Jiang, Y; Yang, G; Meng, F; Yang, W; Hu, J; Ye, L; Shi, C; Wang, C

    2016-06-01

    Inflammatory bowel disease is a group of chronic, incurable inflammatory disorders of the gastrointestinal tract that cause severe diarrhoea, intestinal inflammation, pain, fatigue and weight loss. In this study, we first developed a model of Citrobacter rodentium-induced colitis and then evaluated the protective effects of selected probiotics on inflammation. The results showed that administration of a combination of probiotics including Lactobacillus rhamnosus ATCC 53103, Lactobacillus acidophilus ATCC 4356 and Lactobacillus plantarum A significantly increased the production of CD11c(+) dendritic cells in the spleen (3.62% vs phosphate buffered saline (PBS)-treated control, P<0.01) and mesenteric lymph nodes (MLNs). In addition, the presence of probiotics significantly up-regulated the development of CD4(+)/CD25(+)/Foxp3(+) regulatory T cells in MLNs by approximately 2.07% compared to the effect observed in the PBS-treated control (P<0.01) and down-regulated the expression of inflammatory cytokines, including interleukin-17, tumour necrosis factor-α and interferon-γ, by 0.11, 0.11 and 0.15%, respectively, compared to the effect observed in the PBS-treated control (P<0.01).These effects conferred protection against colitis, as shown by histopathological analyses.

  18. IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.

    PubMed

    Aychek, Tegest; Mildner, Alexander; Yona, Simon; Kim, Ki-Wook; Lampl, Nardy; Reich-Zeliger, Shlomit; Boon, Louis; Yogev, Nir; Waisman, Ari; Cua, Daniel J; Jung, Steffen

    2015-01-01

    Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1(+) mononuclear phagocytes are critical inducers of the innate response to Citrobacter rodentium infection. Specifically, the absence of IL-23 expression in macrophages or CD11b(+) DC results in the impairment of IL-22 production and in acute lethality. Highlighting immunopathology as a death cause, infected animals are rescued by the neutralization of IL-12 or IFNγ. Moreover, mice are also protected when the CD103(+) CD11b(-) DC compartment is rendered deficient for IL-12 production. We show that IL-12 production by colonic CD103(+) CD11b(-) DC is repressed by IL-23. Collectively, in addition to its role in inducing IL-22 production, macrophage-derived or CD103(-) CD11b(+) DC-derived IL-23 is required to negatively control the otherwise deleterious production of IL-12 by CD103(+) CD11b(-) DC. Impairment of this critical mononuclear phagocyte crosstalk results in the generation of IFNγ-producing former TH17 cells and fatal immunopathology.

  19. Effect of substrate concentration and nitrate inhibition on product release and heavy metal removal by a Citrobacter sp.

    SciTech Connect

    Yong, P.; Macaskie, L.E.

    1997-09-20

    The biological treatment of industrial effluent containing heavy metals has received increased attention for its advantages compared to traditional wastewater treatment processes. A Citrobacter sp. accumulates heavy metals as cell-bound metal phosphates, utilizing phosphate released by the enzymatic cleavage of a phosphomonoester substrate. The effect of increased substrate concentration on phosphate release and heavy metal accumulation was evaluated using a stirred tank reactor (STR) and a plug flow reactor (PFR). A significant improvement in metal removal was achieved with increased substrate concentration using immobilized Citrobacter cells in the PFR, which was not observed using free cells in the STR. Nitrate is an inhibitor of the Citrobacter phosphatase. This inhibition was concentration dependent and reversible. The rate of product release was restored by increasing the concentration of substrate (G2P). The ratio of rates of phosphate release under two different conditions (different nitrate and G2P concentrations) can be described by an equation developed from Michaelis-Menten kinetics. The concentration of substrate required for restoration of maximum velocity, V{sub max}, in a batch and continuous-flow system can be predicted by substitution and calculation; this was confirmed by an experiment in model systems using cell suspensions and polyacrylamide gel immobilized cells in a flow-though column. For use in industrial situations it may be uneconomical or infeasible to supply additional substrate. Bioreactor activity was also restored by increasing the flow residence time, in accordance with a Michaelis-Menten-based model to describe removal of lanthanum from nitrate-supplemented flow in a PFR.

  20. Polymeric and compositional properties of novel extracellular microbial polyglucosamine biopolymer from new strain of citrobacter sp. BL-4.

    PubMed

    Kim, Lin-Su; Hong, Soo-Jung; Son, Mi-Kyung; Lee, Yong-Hyun

    2006-02-01

    A novel polyglucosamine polymer, PGB-2, was produced extracellularly from a new strain Citrobacter sp. BL-4 using pH-stat fed batch cultivation. It was composed of 97.3% glucosamine and 2.7% rhamnose; its average molecular weight, solubility in 2% acetic acid and viscosity were 20 kDa, 5 g l(-1) and 2.9 cps, respectively. FT-IR and 1H NMR spectra of PGB-2 revealed a close identity with chitosan from crab shells.

  1. Dynamic Changes in Mucus Thickness and Ion Secretion during Citrobacter rodentium Infection and Clearance

    PubMed Central

    Rodriguez-Piñeiro, Ana M.; Alomran, Ala H. A.; Premaratne, Pushpa; Fernandez, Harvey R.; Banerjee, Debashish; Sjövall, Henrik; Hansson, Gunnar C.; Lindén, Sara K.

    2013-01-01

    Citrobacter rodentium is an attaching and effacing pathogen used as a murine model for enteropathogenic Escherichia coli. The mucus layers are a complex matrix of molecules, and mucus swelling, hydration and permeability are affected by many factors, including ion composition. Here, we used the C. rodentium model to investigate mucus dynamics during infection. By measuring the mucus layer thickness in tissue explants during infection, we demonstrated that the thickness changes dynamically during the course of infection and that its thickest stage coincides with the start of a decrease of bacterial density at day 14 after infection. Although quantitative PCR analysis demonstrated that mucin mRNA increases during early infection, the increased mucus layer thickness late in infection was not explained by increased mRNA levels. Proteomic analysis of mucus did not demonstrate the appearance of additional mucins, but revealed an increased number of proteins involved in defense responses. Ussing chamber-based electrical measurements demonstrated that ion secretion was dynamically altered during the infection phases. Furthermore, the bicarbonate ion channel Bestrophin-2 mRNA nominally increased, whereas the Cftr mRNA decreased during the late infection clearance phase. Microscopy of Muc2 immunostained tissues suggested that the inner striated mucus layer present in the healthy colon was scarce during the time point of most severe infection (10 days post infection), but then expanded, albeit with a less structured appearance, during the expulsion phase. Together with previously published literature, the data implies a model for clearance where a change in secretion allows reformation of the mucus layer, displacing the pathogen to the outer mucus layer, where it is then outcompeted by the returning commensal flora. In conclusion, mucus and ion secretion are dynamically altered during the C. rodentium infection cycle. PMID:24386378

  2. Role of RpoS in the Virulence of Citrobacter rodentium▿

    PubMed Central

    Dong, Tao; Coombes, Brian K.; Schellhorn, Herb E.

    2009-01-01

    Citrobacter rodentium is a mouse enteropathogen that is closely related to Escherichia coli and causes severe colonic hyperplasia and bloody diarrhea. C. rodentium infection requires expression of genes of the locus of enterocyte effacement (LEE) pathogenicity island, which simulates infection by enteropathogenic E. coli and enterohemorrhagic E. coli in the human intestine, providing an effective model for studying enteropathogenesis. In this study we investigated the role of RpoS, the stationary phase sigma factor, in virulence in C. rodentium. Sequence analysis showed that the rpoS gene is highly conserved in C. rodentium and E. coli, exhibiting 92% identity. RpoS was critical for survival under heat shock conditions and during exposure to H2O2 and positively regulated the expression of catalase KatE (HPII). The development of the RDAR (red dry and rough) morphotype, an important virulence trait in E. coli, was also mediated by RpoS in C. rodentium. Unlike E. coli, C. rodentium grew well in the mouse colon, and the wild-type strain colonized significantly better than rpoS mutants. However, a mutation in rpoS conferred a competitive growth advantage over the wild type both in vitro in Luria-Bertani medium and in vivo in the mouse colon. Survival analysis showed that the virulence of an rpoS mutant was attenuated. The expression of genes on the LEE pathogenicity island, which are essential for colonization and virulence, was reduced in the rpoS mutant. In conclusion, RpoS is important for the stress response and is required for full virulence in C. rodentium. PMID:18981255

  3. Evolutionary Adaptation of an AraC-Like Regulatory Protein in Citrobacter rodentium and Escherichia Species

    PubMed Central

    Tan, Aimee; Petty, Nicola K.; Hocking, Dianna; Bennett-Wood, Vicki; Wakefield, Matthew; Praszkier, Judyta; Tauschek, Marija; Yang, Ji

    2015-01-01

    The evolution of pathogenic bacteria is a multifaceted and complex process, which is strongly influenced by the horizontal acquisition of genetic elements and their subsequent expression in their new hosts. A well-studied example is the RegA regulon of the enteric pathogen Citrobacter rodentium. The RegA regulatory protein is a member of the AraC/XylS superfamily, which coordinates the expression of a gene repertoire that is necessary for full pathogenicity of this murine pathogen. Upon stimulation by an exogenous, gut-associated signal, namely, bicarbonate ions, RegA activates the expression of a series of genes, including virulence factors, such as autotransporters, fimbriae, a dispersin-like protein, and the grlRA operon on the locus of enterocyte effacement pathogenicity island. Interestingly, the genes encoding RegA homologues are distributed across the genus Escherichia, encompassing pathogenic and nonpathogenic subtypes. In this study, we carried out a series of bioinformatic, transcriptional, and functional analyses of the RegA regulons of these bacteria. Our results demonstrated that regA has been horizontally transferred to Escherichia spp. and C. rodentium. Comparative studies of two RegA homologues, namely, those from C. rodentium and E. coli SMS-3-5, a multiresistant environmental strain of E. coli, showed that the two regulators acted similarly in vitro but differed in terms of their abilities to activate the virulence of C. rodentium in vivo, which evidently was due to their differential activation of grlRA. Our data indicate that RegA from C. rodentium has strain-specific adaptations that facilitate infection of its murine host. These findings shed new light on the development of virulence by C. rodentium and on the evolution of virulence-regulatory genes of bacterial pathogens in general. PMID:25624355

  4. CD4+ T Cells Drive Goblet Cell Depletion during Citrobacter rodentium Infection

    PubMed Central

    Chan, Justin M.; Bhinder, Ganive; Sham, Ho Pan; Ryz, Natasha; Huang, Tina; Bergstrom, Kirk S.

    2013-01-01

    Both idiopathic and infectious forms of colitis disrupt normal intestinal epithelial cell (IEC) proliferation and differentiation, although the mechanisms involved remain unclear. Recently, we demonstrated that infection by the attaching and effacing murine pathogen Citrobacter rodentium leads to a significant reduction in colonic goblet cell numbers (goblet cell depletion). This pathology depends on T and/or B cells, as Rag1−/− mice do not suffer this depletion during infection, instead suffering high mortality rates. To address the immune mechanisms involved, we reconstituted Rag−/− mice with either CD4+ or CD8+ T cells. Both T cell subsets increased Rag1−/− mouse survival during infection, with mice that received CD8+ T cells developing colonic ulcers but not goblet cell depletion. In contrast, mice that received CD4+ T cells showed goblet cell depletion in concert with exaggerated IEC proliferation. To define the possible involvement of T cell-derived cytokines, we infected gamma interferon receptor gene knockout (IFN-γR−/−) mice and wild-type mice given interleukin 17A (IL-17A) neutralizing antibodies and found that IFN-γ signaling was required for both goblet cell depletion and increased IEC proliferation. Immunostaining revealed that C. rodentium cells preferentially localized to nonhyperplastic crypts containing numerous goblet cells, whereas hyperplastic, goblet cell-depleted crypts appeared protected from infection. To address whether goblet cell depletion benefits the C. rodentium-infected host, we increased goblet cell numbers using the γ-secretase inhibitor dibenzazepine (DBZ), which resulted in greatly increased pathogen burdens and mortality rates. These results demonstrate that goblet cell depletion reflects host immunomodulation of IEC homeostasis and reflects a novel host defense mechanism against mucosal-adherent pathogens. PMID:24101690

  5. The Serine Protease Autotransporter Pic Modulates Citrobacter rodentium Pathogenesis and Its Innate Recognition by the Host.

    PubMed

    Bhullar, Kirandeep; Zarepour, Maryam; Yu, Hongbing; Yang, Hong; Croxen, Matthew; Stahl, Martin; Finlay, B Brett; Turvey, Stuart E; Vallance, Bruce A

    2015-07-01

    Bacterial pathogens produce a number of autotransporters that possess diverse functions. These include the family of serine protease autotransporters of Enterobacteriaceae (SPATEs) produced by enteric pathogens such as Shigella flexneri and enteroaggregative Escherichia coli. Of these SPATEs, one termed "protein involved in colonization," or Pic, has been shown to possess mucinase activity in vitro, but to date, its role in in vivo enteric pathogenesis is unknown. Testing a pic null (ΔpicC) mutant in Citrobacter rodentium, a natural mouse pathogen, found that the C. rodentium ΔpicC strain was impaired in its ability to degrade mucin in vitro compared to the wild type. Upon infection of mice, the ΔpicC mutant exhibited a hypervirulent phenotype with dramatically heavier pathogen burdens found in intestinal crypts. ΔpicC mutant-infected mice suffered greater barrier disruption and more severe colitis and weight loss, necessitating their euthanization between 10 and 14 days postinfection. Notably, the virulence of the ΔpicC mutant was normalized when the picC gene was restored; however, a PicC point mutant causing loss of mucinase activity did not replicate the ΔpicC phenotype. Exploring other aspects of PicC function, the ΔpicC mutant was found to aggregate to higher levels in vivo than wild-type C. rodentium. Moreover, unlike the wild type, the C. rodentium ΔpicC mutant had a red, dry, and rough (RDAR) morphology in vitro and showed increased activation of the innate receptor Toll-like receptor 2 (TLR2). Interestingly, the C. rodentium ΔpicC mutant caused a degree of pathology similar to that of wild-type C. rodentium when infecting TLR2-deficient mice, showing that despite its mucinase activity, PicC's major role in vivo may be to limit C. rodentium's stimulation of the host's innate immune system.

  6. Microbial degradation of Paclitaxel using Citrobacter amalonaticus Rashtia isolated from pharmaceutical wastewater: kinetic and thermodynamic study.

    PubMed

    Zamani, Hojjatolah; Grakoee, Seyed Reza; Rakhshaee, Roohan

    2016-08-01

    Paclitaxel is a highly toxic anticancer agent which is used in a wide range against ovarian, breast, lung, and prostate cancers. Paclitaxel is manufactured recently in the north of Iran which may lead to the introduction of the drug into the environment via pharmaceutical wastewater. To our knowledge, Paclitaxel degradation is currently performed using physicochemical methods and biological degradation of Paclitaxel has not been reported. In this study, a Paclitaxel degrading bacterium was isolated from pharmaceutical wastewater for the first time. The bacterium was identified using biochemical and molecular assays and its Paclitaxel degradation potential was evaluated using High Performance Liquid Chromatography (HPLC). In addition, kinetic and thermodynamic study of Paclitaxel degradation at different experimental conditions was performed. A Citrobacter species named as C. amalonaticus Rashtia able to degrade and utilize Paclitaxel as the sole carbon source was isolated. The isolated strain tolerated high level concentration of Paclitaxel (0.4 mg/mL) in liquid culture media and was able to degrade spillage-level concentrations of the drug (0.01-0.1 mg/mL) with 87-93 % efficacy under aerobic condition. Kinetic and thermodynamic study at different pHs (4.0, 7.0 and 10.0) and temperatures (285, 295 and 310 K) revealed that Paclitaxel degradation is a non-spontaneous process and the highest rate constant was observed in the basic condition and at the highest temperature. The ΔG values at 285, 295 and 310 K were determined 103.3, 105.9 and 109.9 kJ/mol, respectively. In addition, The ΔH and activation energy (Ea) of the process were determined +28.7 kJ/mol and +30.87 kJ/mol, respectively. PMID:27339310

  7. Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection

    PubMed Central

    Habibzay, Maryam; Glegola-Madejska, Izabela; Guenot, Marianne; Collins, James W.

    2015-01-01

    The hallmarks of enteropathogenic Escherichia coli (EPEC) infection are formation of attaching and effacing (A/E) lesions on mucosal surfaces and actin-rich pedestals on cultured cells, both of which are dependent on the type III secretion system effector Tir. Following translocation into cultured cells and clustering by intimin, Tir Y474 is phosphorylated, leading to recruitment of Nck, activation of N-WASP, and actin polymerization via the Arp2/3 complex. A secondary, weak, actin polymerization pathway is triggered via an NPY motif (Y454). Importantly, Y454 and Y474 play no role in A/E lesion formation on mucosal surfaces following infection with the EPEC-like mouse pathogen Citrobacter rodentium. In this study, we investigated the roles of Tir segments located upstream of Y451 and downstream of Y471 in C. rodentium colonization and A/E lesion formation. We also tested the role that Tir residues Y451 and Y471 play in host immune responses to C. rodentium infection. We found that deletion of amino acids 382 to 462 or 478 to 547 had no impact on the ability of Tir to mediate A/E lesion formation, although deletion of amino acids 478 to 547 affected Tir translocation. Examination of enterocytes isolated from infected mice revealed that a C. rodentium strain expressing Tir_Y451A/Y471A recruited significantly fewer neutrophils to the colon and triggered less colonic hyperplasia on day 14 postinfection than the wild-type strain. Consistently, enterocytes isolated from mice infected with C. rodentium expressing Tir_Y451A/Y471A expressed significantly less CXCL1. These result show that Tir-induced actin remodeling plays a direct role in modulation of immune responses to C. rodentium infection. PMID:26077760

  8. Role of class 1 serine protease autotransporter in the pathogenesis of Citrobacter rodentium colitis.

    PubMed

    Vijayakumar, Vidhya; Santiago, Araceli; Smith, Rachel; Smith, Mark; Robins-Browne, Roy M; Nataro, James P; Ruiz-Perez, Fernando

    2014-06-01

    A growing family of virulence factors called serine protease autotransporters of Enterobacteriaceae (SPATEs) are secreted by Shigella, Salmonella, and Escherichia coli pathotypes. SPATEs are subdivided into class 1 and class 2 based on structural features and phylogenetics. Class 1 SPATEs induce cytopathic effects in numerous epithelial cell lines, and several have been shown to cleave the cytoskeletal protein spectrin in vitro. However, to date the in vivo role of class 1 SPATEs in enteric pathogenesis is unknown. Citrobacter rodentium, a natural mouse pathogen, has recently been shown to harbor class 1 and class 2 SPATEs. To better understand the contribution of class 1 SPATEs in enteric infection, we constructed a class 1 SPATE null mutant (Δcrc1) in C. rodentium. Upon infection of C57BL/6 mice, the Δcrc1 mutant exhibited a hypervirulent, hyperinflammatory phenotype compared with its parent, accompanied by greater weight loss and a trend toward increased mortality in young mice; the effect was reversed when the crc1 gene was restored. Using flow cytometry, we observed increased infiltration of T cells, B cells, and neutrophils into the lamina propria of the distal colon in mice fed the Δcrc1 mutant, starting as early as 5 days after infection. No significant difference in epithelial cytotoxicity was observed. Reverse transcription-PCR (RT-PCR) analysis of distal colonic tissue on day 10 postinfection showed significant increases in mRNA encoding cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), IL-1β, and inducible nitric oxide synthase (iNOS) but not in mRNA encoding IL-17, IL-4, or IL-10 in the Δcrc1 mutant-infected mice. Our data suggest a previously unsuspected role for class 1 SPATEs in enteric infection.

  9. Evolutionary adaptation of an AraC-like regulatory protein in Citrobacter rodentium and Escherichia species.

    PubMed

    Tan, Aimee; Petty, Nicola K; Hocking, Dianna; Bennett-Wood, Vicki; Wakefield, Matthew; Praszkier, Judyta; Tauschek, Marija; Yang, Ji; Robins-Browne, Roy

    2015-04-01

    The evolution of pathogenic bacteria is a multifaceted and complex process, which is strongly influenced by the horizontal acquisition of genetic elements and their subsequent expression in their new hosts. A well-studied example is the RegA regulon of the enteric pathogen Citrobacter rodentium. The RegA regulatory protein is a member of the AraC/XylS superfamily, which coordinates the expression of a gene repertoire that is necessary for full pathogenicity of this murine pathogen. Upon stimulation by an exogenous, gut-associated signal, namely, bicarbonate ions, RegA activates the expression of a series of genes, including virulence factors, such as autotransporters, fimbriae, a dispersin-like protein, and the grlRA operon on the locus of enterocyte effacement pathogenicity island. Interestingly, the genes encoding RegA homologues are distributed across the genus Escherichia, encompassing pathogenic and nonpathogenic subtypes. In this study, we carried out a series of bioinformatic, transcriptional, and functional analyses of the RegA regulons of these bacteria. Our results demonstrated that regA has been horizontally transferred to Escherichia spp. and C. rodentium. Comparative studies of two RegA homologues, namely, those from C. rodentium and E. coli SMS-3-5, a multiresistant environmental strain of E. coli, showed that the two regulators acted similarly in vitro but differed in terms of their abilities to activate the virulence of C. rodentium in vivo, which evidently was due to their differential activation of grlRA. Our data indicate that RegA from C. rodentium has strain-specific adaptations that facilitate infection of its murine host. These findings shed new light on the development of virulence by C. rodentium and on the evolution of virulence-regulatory genes of bacterial pathogens in general.

  10. The CpxRA two-component system is essential for Citrobacter rodentium virulence.

    PubMed

    Thomassin, Jenny-Lee; Giannakopoulou, Natalia; Zhu, Lei; Gross, Jeremy; Salmon, Kristiana; Leclerc, Jean-Mathieu; Daigle, France; Le Moual, Hervé; Gruenheid, Samantha

    2015-05-01

    Citrobacter rodentium is a murine intestinal pathogen used as a model for the foodborne human pathogens enterohemorrhagic Escherichia coli and enteropathogenic E. coli. During infection, these pathogens use two-component signal transduction systems to detect and adapt to changing environmental conditions. In E. coli, the CpxRA two-component signal transduction system responds to envelope stress by modulating the expression of a myriad of genes. Quantitative real-time PCR showed that cpxRA was expressed in the colon of C57BL/6J mice infected with C. rodentium. To determine whether CpxRA plays a role during C. rodentium infection, a cpxRA deletion strain was generated and found to have a colonization defect during infection. This defect was independent of an altered growth rate or a defective type III secretion system, and single-copy chromosomal complementation of cpxRA restored virulence. The C. rodentium strains were then tested in C3H/HeJ mice, a lethal intestinal infection model. Mice infected with the ΔcpxRA strain survived infection, whereas mice infected with the wild-type or complemented strains succumbed to infection. Furthermore, we found that the cpxRA expression level was higher during early infection than at a later time point. Taken together, these data demonstrate that the CpxRA two-component signal transduction system is essential for the in vivo virulence of C. rodentium. In addition, these data suggest that fine-tuned cpxRA expression is important for infection. This is the first study that identifies a C. rodentium two-component transduction system required for pathogenesis. This study further indicates that CpxRA is an interesting target for therapeutics against enteric pathogens.

  11. Microbial degradation of Paclitaxel using Citrobacter amalonaticus Rashtia isolated from pharmaceutical wastewater: kinetic and thermodynamic study.

    PubMed

    Zamani, Hojjatolah; Grakoee, Seyed Reza; Rakhshaee, Roohan

    2016-08-01

    Paclitaxel is a highly toxic anticancer agent which is used in a wide range against ovarian, breast, lung, and prostate cancers. Paclitaxel is manufactured recently in the north of Iran which may lead to the introduction of the drug into the environment via pharmaceutical wastewater. To our knowledge, Paclitaxel degradation is currently performed using physicochemical methods and biological degradation of Paclitaxel has not been reported. In this study, a Paclitaxel degrading bacterium was isolated from pharmaceutical wastewater for the first time. The bacterium was identified using biochemical and molecular assays and its Paclitaxel degradation potential was evaluated using High Performance Liquid Chromatography (HPLC). In addition, kinetic and thermodynamic study of Paclitaxel degradation at different experimental conditions was performed. A Citrobacter species named as C. amalonaticus Rashtia able to degrade and utilize Paclitaxel as the sole carbon source was isolated. The isolated strain tolerated high level concentration of Paclitaxel (0.4 mg/mL) in liquid culture media and was able to degrade spillage-level concentrations of the drug (0.01-0.1 mg/mL) with 87-93 % efficacy under aerobic condition. Kinetic and thermodynamic study at different pHs (4.0, 7.0 and 10.0) and temperatures (285, 295 and 310 K) revealed that Paclitaxel degradation is a non-spontaneous process and the highest rate constant was observed in the basic condition and at the highest temperature. The ΔG values at 285, 295 and 310 K were determined 103.3, 105.9 and 109.9 kJ/mol, respectively. In addition, The ΔH and activation energy (Ea) of the process were determined +28.7 kJ/mol and +30.87 kJ/mol, respectively.

  12. Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection.

    PubMed

    Crepin, Valerie F; Habibzay, Maryam; Glegola-Madejska, Izabela; Guenot, Marianne; Collins, James W; Frankel, Gad

    2015-09-01

    The hallmarks of enteropathogenic Escherichia coli (EPEC) infection are formation of attaching and effacing (A/E) lesions on mucosal surfaces and actin-rich pedestals on cultured cells, both of which are dependent on the type III secretion system effector Tir. Following translocation into cultured cells and clustering by intimin, Tir Y474 is phosphorylated, leading to recruitment of Nck, activation of N-WASP, and actin polymerization via the Arp2/3 complex. A secondary, weak, actin polymerization pathway is triggered via an NPY motif (Y454). Importantly, Y454 and Y474 play no role in A/E lesion formation on mucosal surfaces following infection with the EPEC-like mouse pathogen Citrobacter rodentium. In this study, we investigated the roles of Tir segments located upstream of Y451 and downstream of Y471 in C. rodentium colonization and A/E lesion formation. We also tested the role that Tir residues Y451 and Y471 play in host immune responses to C. rodentium infection. We found that deletion of amino acids 382 to 462 or 478 to 547 had no impact on the ability of Tir to mediate A/E lesion formation, although deletion of amino acids 478 to 547 affected Tir translocation. Examination of enterocytes isolated from infected mice revealed that a C. rodentium strain expressing Tir_Y451A/Y471A recruited significantly fewer neutrophils to the colon and triggered less colonic hyperplasia on day 14 postinfection than the wild-type strain. Consistently, enterocytes isolated from mice infected with C. rodentium expressing Tir_Y451A/Y471A expressed significantly less CXCL1. These result show that Tir-induced actin remodeling plays a direct role in modulation of immune responses to C. rodentium infection.

  13. Effects of nutritional and environmental conditions on planktonic growth and biofilm formation of Citrobacter werkmanii BF-6.

    PubMed

    Zhou, Gang; Li, Long-jie; Shi, Qing-shan; Ouyang, You-sheng; Chen, Yi-ben; Hu, Wen-feng

    2013-12-01

    Citrobacter sp. is a cause of significant opportunistic nosocomial infection and is frequently found in human and animal feces, soil, and sewage water, and even in industrial waste or putrefaction. Biofilm formation is an important virulence trait of Citrobacter sp. pathogens but the process and characteristics of this formation are unclear. Therefore, we employed in vitro assays to study the nutritional and environmental parameters that might influence biofilm formation of C. werkmanii BF-6 using 96-well microtiter plates. In addition, we detected the relative transcript levels of biofilm formation genes by RT-PCR. Our results indicated that the capacity of C. werkmanii BF-6 to form biofilms was affected by culture temperature, media, time, pH, and the osmotic agents glucose, sucrose, NaCl, and KCl. Confocal laser scanning microscopy results illustrated that the structure of biofilms and extracellular polysaccharide was influenced by 100 mM NaCl or 100 mM KCl. In addition, nine biofilm formation genes (bsmA, bssR, bssS, csgD, csgE, csgF, mrkA, mrkB, and mrkE) were found to contribute to planktonic and biofilm growth. Our data suggest that biofilm formation by C. werkmanii BF-6 is affected by nutritional and environmental factors, which could pave the way to the prevention and elimination of biofilm formation using proper strategies.

  14. Genome Sequence of Citrobacter sp. CtB7.12, Isolated from the Gut of the Desert Subterranean Termite Heterotermes aureus

    PubMed Central

    Fontes-Perez, Héctor; Olvera-García, Myrna; Chávez-Martínez, America; Rodriguez-Almeida, Felipe A.; Arzola-Alvarez, Claudio A.

    2015-01-01

    The draft genome of Citrobacter sp. CtB7.12, isolated from termite gut, is presented here. This organism has been reported as a cellulolytic bacterium, which is biotechnologically important because it can be used as a gene donor for the ethanol and biofuel industries. PMID:26543121

  15. Development of a Rapid and Accurate Identification Method for Citrobacter Species Isolated from Pork Products Using a Matrix-Assisted Laser-Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS).

    PubMed

    Kwak, Hye-Lim; Han, Sun-Kyung; Park, Sunghoon; Park, Si Hong; Shim, Jae-Yong; Oh, Mihwa; Ricke, Steven C; Kim, Hae-Yeong

    2015-09-01

    Previous detection methods for Citrobacter are considered time consuming and laborious. In this study, we have developed a rapid and accurate detection method for Citrobacter species in pork products, using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). A total of 35 Citrobacter strains were isolated from 30 pork products and identified by both MALDI-TOF MS and 16S rRNA gene sequencing approaches. All isolates were identified to the species level by the MALDI-TOF MS, while 16S rRNA gene sequencing results could not discriminate them clearly. These results confirmed that MALDI-TOF MS is a more accurate and rapid detection method for the identification of Citrobacter species.

  16. Malachite green bioremoval by a newly isolated strain Citrobacter sedlakii RI11; enhancement of the treatment by biosurfactant addition.

    PubMed

    Mnif, Inès; Fendri, Raouia; Ghribi, Dhouha

    2015-01-01

    Citrobacter sedlackii RI11, isolated from acclimated textile effluent after selective enrichment on synthetic dyes, was assessed for malachite green (MG) biotreatment potency. Results indicate that this bacterium has potential for use in effective treatment of MG contaminated wastewaters under shaking conditions at neutral and alkaline pH value, characteristic of typical textile effluents. Also, the newly isolated strain can tolerate higher doses of dye and decolorize up to 1,000 mg/l of dye. When used as microbial surfactant to enhance MG biodecolorization, Bacillus subtilis SPB1-derived lipopeptide accelerated the decolorization rate and maximized the decolorization efficiency at an optimal concentration of biosurfactant of about 0.075%. Studies ensured that MG removal by this strain could be due to biodegradation and/or adsorption. Results on germination potencies of different seeds using the treated dyes under different conditions favor the use of SPB1 biosurfactant for the treatment of MG. PMID:26465297

  17. Malachite green bioremoval by a newly isolated strain Citrobacter sedlakii RI11; enhancement of the treatment by biosurfactant addition.

    PubMed

    Mnif, Inès; Fendri, Raouia; Ghribi, Dhouha

    2015-01-01

    Citrobacter sedlackii RI11, isolated from acclimated textile effluent after selective enrichment on synthetic dyes, was assessed for malachite green (MG) biotreatment potency. Results indicate that this bacterium has potential for use in effective treatment of MG contaminated wastewaters under shaking conditions at neutral and alkaline pH value, characteristic of typical textile effluents. Also, the newly isolated strain can tolerate higher doses of dye and decolorize up to 1,000 mg/l of dye. When used as microbial surfactant to enhance MG biodecolorization, Bacillus subtilis SPB1-derived lipopeptide accelerated the decolorization rate and maximized the decolorization efficiency at an optimal concentration of biosurfactant of about 0.075%. Studies ensured that MG removal by this strain could be due to biodegradation and/or adsorption. Results on germination potencies of different seeds using the treated dyes under different conditions favor the use of SPB1 biosurfactant for the treatment of MG.

  18. [NiFe]Hydrogenase from Citrobacter sp. S-77 surpasses platinum as an electrode for H2 oxidation reaction.

    PubMed

    Matsumoto, Takahiro; Eguchi, Shigenobu; Nakai, Hidetaka; Hibino, Takashi; Yoon, Ki-Seok; Ogo, Seiji

    2014-08-18

    Reported herein is an electrode for dihydrogen (H2) oxidation, and it is based on [NiFe]Hydrogenase from Citrobacter sp. S-77 ([NiFe]S77). It has a 637 times higher mass activity than Pt (calculated based on 1 mg of [NiFe]S77 or Pt) at 50 mV in a hydrogen half-cell. The [NiFe]S77 electrode is also stable in air and, unlike Pt, can be recovered 100 % after poisoning by carbon monoxide. Following characterization of the [NiFe]S77 electrode, a fuel cell comprising a [NiFe]S77 anode and Pt cathode was constructed and shown to have a a higher power density than that achievable by Pt. PMID:24895095

  19. Investigation of Host and Pathogen Contributions to Infectious Colitis Using the Citrobacter rodentium Mouse Model of Infection.

    PubMed

    Bosman, Else S; Chan, Justin M; Bhullar, Kirandeep; Vallance, Bruce A

    2016-01-01

    Citrobacter rodentium is used as a model organism to study enteric bacterial infections in mice. Infection occurs via the oral-fecal route and results in the pathogen forming attaching and effacing lesions on infected epithelial cells. Moreover, infection leads to a subsequent host-mediated form of colitis. C. rodentium infection is thus an excellent model to study infectious colitis in vivo, while the ability to genetically manipulate C. rodentium virulence genes provides the opportunity to develop clear insights into the pathogenesis of this and related infectious microbes. This chapter outlines the basic techniques involved in setting up a C. rodentium infection in mice and several different methodologies to assess the severity of the infection.

  20. [NiFe]Hydrogenase from Citrobacter sp. S-77 surpasses platinum as an electrode for H2 oxidation reaction.

    PubMed

    Matsumoto, Takahiro; Eguchi, Shigenobu; Nakai, Hidetaka; Hibino, Takashi; Yoon, Ki-Seok; Ogo, Seiji

    2014-08-18

    Reported herein is an electrode for dihydrogen (H2) oxidation, and it is based on [NiFe]Hydrogenase from Citrobacter sp. S-77 ([NiFe]S77). It has a 637 times higher mass activity than Pt (calculated based on 1 mg of [NiFe]S77 or Pt) at 50 mV in a hydrogen half-cell. The [NiFe]S77 electrode is also stable in air and, unlike Pt, can be recovered 100 % after poisoning by carbon monoxide. Following characterization of the [NiFe]S77 electrode, a fuel cell comprising a [NiFe]S77 anode and Pt cathode was constructed and shown to have a a higher power density than that achievable by Pt.

  1. Influence of NleH effector expression, host genetics, and inflammation on Citrobacter rodentium colonization of mice.

    PubMed

    Feuerbacher, Leigh Ann; Hardwidge, Philip R

    2014-05-01

    The Escherichia coli NleH1 and NleH2 virulence proteins differentially regulate host transcription of innate immunity genes. The mouse pathogen Citrobacter rodentium encodes one NleH protein, which functions equivalently to E. coli NleH1. We examined the impact of host genetics and intestinal inflammation on the contribution of NleH to C. rodentium colonization of mice differing in LPS responsiveness. NleH expression was detrimental to C. rodentium in C57BL/10ScNJ mice, which do not mount LPS-induced inflammatory responses. This phenotype was reversed if inflammation was induced by chemical means. C. rodentium that expressed both E. coli NleH1 and NleH2 was hypervirulent in C3H/HeJ mice.

  2. Molybdenum-containing membrane-bound formate dehydrogenase isolated from Citrobacter sp. S-77 having high stability against oxygen, pH, and temperature.

    PubMed

    Nguyen, Nga T; Yatabe, Takeshi; Yoon, Ki-Seok; Ogo, Seiji

    2014-10-01

    Membrane-bound formate dehydrogenase (FDH) was purified to homogeneity from a facultative anaerobic bacterium Citrobacter sp. S-77. The FDH from Citrobacter sp. S-77 (FDHS77) was a monomer with molecular mass of approximately 150 kDa. On SDS-PAGE, the purified FDHS77 showed as three different protein bands with molecular mass of approximately 95, 87, and 32 kDa, respectively. Based on the N-terminal amino acid sequence analysis, the sequence alignments observed for the 87 kDa protein band were identical to that of the large subunit of 95 kDa, indicating that the purified FDHS77 consisted of two subunits; a 95 kDa large subunit and a 32 kDa small subunit. The purified FDHS77 in this purification did not contain a heme b subunit, but the FDHS77 showed significant activity for formate oxidation, determined by the Vmax of 30.4 U/mg using benzyl viologen as an electron acceptor. The EPR and ICP-MS spectra indicate that the FDHS77 is a molybdenum-containing enzyme, displaying a remarkable O2-stability along with thermostability and pH resistance. This is the first report of the purification and characterization of a FDH from Citrobacter species.

  3. Bicarbonate-mediated transcriptional activation of divergent operons by the virulence regulatory protein, RegA, from Citrobacter rodentium.

    PubMed

    Yang, Ji; Hart, Emily; Tauschek, Marija; Price, G Dean; Hartland, Elizabeth L; Strugnell, Richard A; Robins-Browne, Roy M

    2008-04-01

    Regulation of virulence gene expression plays a central role in the pathogenesis of enteric bacteria as they encounter diverse environmental conditions in the gastrointestinal tract of their hosts. In this study, we investigated environmental regulation of two putative virulence determinants adcA and kfc by RegA, an AraC/XylS-like regulator, from Citrobacter rodentium, and identified bicarbonate as the environmental signal which induced transcription of adcA and kfc through RegA. Primer extension experiments showed that adcA and kfc were divergently transcribed from sigma(70) promoters. In vivo and in vitro experiments demonstrated that bicarbonate facilitated and stabilized the binding of RegA to an operator located between the two promoters. The interaction of RegA with its DNA target resulted in the formation of a nucleosome-like structure, which evidently displaced the histone-like proteins, H-NS and StpA, from the adcA and kfc promoter regions, leading to transcriptional derepression. In addition, our results indicated that RegA also behaved as a Class I activator by directly stimulating transcription initiation by RNA polymerase. This is the first report to describe the molecular mechanism by which an environmental chemical stimulates transcription of virulence-associated genes of an enteric pathogen through an AraC/XlyS-like activator.

  4. Social stress-enhanced severity of Citrobacter rodentium induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri

    PubMed Central

    Mackos, Amy R.; Galley, Jeffrey D.; Eubank, Timothy D.; Easterling, Robert S.; Parry, Nicola M.; Fox, James G.; Lyte, Mark; Bailey, Michael T.

    2015-01-01

    Psychological stressors are known to affect colonic diseases but the mechanisms by which this occurs, and whether probiotics can prevent stressor effects, are not understood. Because inflammatory monocytes that traffic into the colon can exacerbate colitis, we tested whether CCL2, a chemokine involved in monocyte recruitment, was necessary for stressor-induced exacerbation of infectious colitis. Mice were exposed to a social disruption stressor that entails repeated social defeat. During stressor exposure, mice were orally challenged with Citrobacter rodentium to induce a colonic inflammatory response. Exposure to the stressor during challenge resulted in significantly higher colonic pathogen levels, translocation to the spleen, increases in colonic macrophages, and increases in inflammatory cytokines and chemokines. The stressor-enhanced severity of C. rodentium-induced colitis was not evident in CCL2−/− mice, indicating the effects of the stressor are CCL2-dependent. Additionally, we tested whether probiotic intervention could attenuate stressor-enhanced infectious colitis by reducing monocyte/macrophage accumulation. Treating mice with probiotic Lactobacillus reuteri reduced CCL2 mRNA levels in the colon, and attenuated stressor-enhanced infectious colitis. These data demonstrate that probiotic L. reuteri can prevent the exacerbating effects of stressor exposure on pathogen-induced colitis, and suggest that one mechanism by which this occurs is through a down-regulation of the chemokine CCL2. PMID:26422754

  5. Biochemical characterization of a bifunctional acetaldehyde-alcohol dehydrogenase purified from a facultative anaerobic bacterium Citrobacter sp. S-77.

    PubMed

    Tsuji, Kohsei; Yoon, Ki-Seok; Ogo, Seiji

    2016-03-01

    Acetaldehyde-alcohol dehydrogenase (ADHE) is a bifunctional enzyme consisting of two domains of an N-terminal acetaldehyde dehydrogenase (ALDH) and a C-terminal alcohol dehydrogenase (ADH). The enzyme is known to be important in the cellular alcohol metabolism. However, the role of coenzyme A-acylating ADHE responsible for ethanol production from acetyl-CoA remains uncertain. Here, we present the purification and biochemical characterization of an ADHE from Citrobacter sp. S-77 (ADHE(S77)). Interestingly, the ADHE(S77) was unable to be solubilized from membrane with detergents either 1% Triton X-100 or 1% Sulfobetaine 3-12. However, the enzyme was easily dissociated from membrane by high-salt buffers containing either 1.0 M NaCl or (NH(4))(2)SO(4) without detergents. The molecular weight of a native protein was estimated as approximately 400 kDa, consisting of four identical subunits of 96.3 kDa. Based on the specific activity and kinetic analysis, the ADHES77 tended to have catalytic reaction towards acetaldehyde elimination rather than acetaldehyde formation. Our experimental observation suggests that the ADHES77 may play a pivotal role in modulating intracellular acetaldehyde concentration.

  6. Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium-induced colitis.

    PubMed

    Ryz, Natasha R; Lochner, Arion; Bhullar, Kirandeep; Ma, Caixia; Huang, Tina; Bhinder, Ganive; Bosman, Else; Wu, Xiujuan; Innis, Sheila M; Jacobson, Kevan; Vallance, Bruce A

    2015-11-01

    Vitamin D deficiency affects more that 1 billion people worldwide. Although thought to increase risk of bacterial infections, the importance of vitamin D on host defense against intestinal bacterial pathogens is currently unclear since injection of the active form of vitamin D, 1,25(OH)2D3, increased susceptibility to the enteric bacterial pathogen Citrobacter rodentium by suppressing key immune/inflammatory factors. To further characterize the role of vitamin D during bacteria-induced colitis, we fed weanling mice either vitamin D3-deficient or vitamin D3-sufficient diets for 5 wk and then challenged them with C. rodentium. Vitamin D3-deficient mice lost significantly more body weight, carried higher C. rodentium burdens, and developed worsened histological damage. Vitamin D3-deficient mice also suffered greater bacterial translocation to extra-intestinal tissues, including mesenteric lymph nodes, spleen, and liver. Intestinal tissues of infected vitamin D3-deficient mice displayed increased inflammatory cell infiltrates as well as significantly higher gene transcript levels of inflammatory mediators TNF-α, IL-1β, IL-6, TGF-β, IL-17A, and IL-17F as well as the antimicrobial peptide REG3γ. Notably, these exaggerated inflammatory responses accelerated the loss of commensal microbes and were associated with an impaired ability to detoxify bacterial lipopolysaccharide. Overall, these studies show that dietary-induced vitamin D deficiency exacerbates intestinal inflammatory responses to infection, also impairing host defense.

  7. Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner.

    PubMed

    Jain, Umang; Cao, Qi; Thomas, Nikhil A; Woodruff, Trent M; Schwaeble, Wilhelm J; Stover, Cordula M; Stadnyk, Andrew W

    2015-04-01

    Citrobacter rodentium is an attaching and effacing mouse pathogen that models enteropathogenic and enterohemorrhagic Escherichia coli in humans. The complement system is an important innate defense mechanism; however, only scant information is available about the role of complement proteins during enteric infections. In this study, we examined the impact of the lack of properdin, a positive regulator of complement, in C. rodentium-induced colitis. Following infection, properdin knockout (P(KO)) mice had increased diarrhea and exacerbated inflammation combined with defective epithelial cell-derived IL-6 and greater numbers of colonizing bacteria. The defect in the mucosal response was reversed by administering exogenous properdin to P(KO) mice. Then, using in vitro and in vivo approaches, we show that the mechanism behind the exacerbated inflammation of P(KO) mice is due to a failure to increase local C5a levels. We show that C5a directly stimulates IL-6 production from colonic epithelial cells and that inhibiting C5a in infected wild-type mice resulted in defective epithelial IL-6 production and exacerbated inflammation. These outcomes position properdin early in the response to an infectious challenge in the colon, leading to complement activation and C5a, which in turn provides protection through IL-6 expression by the epithelium. Our results unveil a previously unappreciated mechanism of intestinal homeostasis involving complement, C5a, and IL-6 during bacteria-triggered epithelial injury.

  8. Surfactant-modified fatty acid composition of Citrobacter sp. SA01 and its effect on phenanthrene transmembrane transport.

    PubMed

    Li, Feng; Zhu, Lizhong

    2014-07-01

    The effects of the surfactants, Tween 80 and sodium dodecyl benzene sulfonate (SDBS) on a membrane's fatty acid composition and the transmembrane transport of phenanthrene were investigated. The results indicated that both surfactants could modify the composition of fatty acids of Citrobacter sp. Strain SA01 cells, 50 mg L(-1) of both surfactants changed the composition of the fatty acids the most, increasing the amount of unsaturated fatty acids. The comparison of fatty acid profiles with diphenylhexatriene fluorescence anisotropy, a probe for plasma membrane fluidity, suggested that an increased amount of unsaturated fatty acids corresponded to greater membrane fluidity. In addition, increased unsaturated fatty acids promoted phenanthrene to partition from the extracellular matrix to cell debris, which increased reverse partitioning from the cell debris to the cytochylema. The results of this study were expected in that the addition of a surfactant is a simple and effective method for accelerating the rate-limiting step of transmembrane transport of hydrophobic organic compounds (HOCs) in bioremediation.

  9. Polarizing the T helper 17 response in Citrobacter rodentium infection via expression of resistin-like molecule α.

    PubMed

    Chen, Gang; Chan, Alexander J; Chung, Josiah I; Jang, Jessica C; Osborne, Lisa C; Nair, Meera G

    2014-01-01

    Citrobacter rodentium infection is a murine model of pathogenic Escherichia coli infection that allows investigation of the cellular and molecular mechanisms involved in host-protective immunity and bacterial-induced intestinal inflammation. We recently demonstrated that following C. rodentium infection, the absence of Resistin-Like Molecule (RELM) α resulted in attenuated Th17 cell responses and reduced intestinal inflammation with minimal effects on bacterial clearance. In this addendum, we investigated the cytokine modulatory effects of RELMα and RELMα expression in the intestinal mucosa following C. rodentium infection. We show that in addition to promoting Th17 cytokine responses, RELMα inhibits Th2 cytokine expression and Th2-cytokine effector macrophage responses in the C. rodentium-infected colons. Second, utilizing reporter C. rodentium, we examined RELMα expression and macrophage recruitment at the host pathogen interface. We observed infection-induced macrophage infiltration and RELMα expression by intestinal epithelial cells. The influence of infection-induced RELMα on macrophage recruitment in the intestine is discussed.

  10. CXCL9 contributes to antimicrobial protection of the gut during citrobacter rodentium infection independent of chemokine-receptor signaling.

    PubMed

    Reid-Yu, Sarah A; Tuinema, Brian R; Small, Cherrie N; Xing, Lydia; Coombes, Brian K

    2015-02-01

    Chemokines have been shown to be effective bactericidal molecules against a variety of bacteria and fungi in vitro. These direct antimicrobial effects are independent of their chemotactic activities involving immunological receptors. However, the direct biological role that these proteins may play in host defense, particularly against intestinal pathogens, is poorly understood. Here, we show that CXCL9, an ELR- chemokine, exhibits direct antimicrobial activity against Citrobacter rodentium, an attaching/effacing pathogen that infects the gut mucosa. Inhibition of this antimicrobial activity in vivo using anti-CXCL9 antibodies increases host susceptibility to C. rodentium infection with pronounced bacterial penetration into crypts, increased bacterial load, and worsened tissue pathology. Using Rag1(-/-) mice and CXCR3(-/-) mice, we demonstrate that the role for CXCL9 in protecting the gut mucosa is independent of an adaptive response or its immunological receptor, CXCR3. Finally, we provide evidence that phagocytes function in tandem with NK cells for robust CXCL9 responses to C. rodentium. These findings identify a novel role for the immune cell-derived CXCL9 chemokine in directing a protective antimicrobial response in the intestinal mucosa.

  11. Dysbiosis caused by vitamin D receptor deficiency confers colonization resistance to Citrobacter rodentium through modulation of innate lymphoid cells.

    PubMed

    Chen, J; Waddell, A; Lin, Y-D; Cantorna, M T

    2015-05-01

    Vitamin D receptor (VDR) knockout (KO) mice had fewer Citrobacter rodentium in the feces than wild-type (WT) mice and the kinetics of clearance was faster in VDR KO than WT mice. VDR KO mice had more interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) and more antibacterial peptides than WT mice. The increased ILCs in the VDR KO mice was a cell-autonomous effect of VDR deficiency on ILC frequencies. Bone marrow (BM) transplantation from VDR KO mice into WT resulted in higher ILCs and colonization resistance of the WT mice. Disruption of the gut microbiota using antibiotics in VDR KO mice reversed colonization resistance to C. rodentium infection. Confirming the role of the microbiota in the colonization resistance of VDR KO mice, transfer of the VDR KO microbiota to WT germ-free mice resulted in colonization resistance. Once colonization resistance was overcome, VDR KO mice had increased susceptibility to C. rodentium. VDR expression is a regulator of ILC frequencies, IL-22, dysbiosis, and C. rodentium susceptibility.

  12. A New Episomic Element Controlling Fermentative Metabolism and Excretion of Amino Acids by Citrobacter intermedium C3

    PubMed Central

    Pares, R.; Guinea, J.; Hernandez, S.; Valoix, Josefina; Jofre, J.

    1974-01-01

    Glutamate excretion by colonies of Citrobacter intermedium C3 was detected by using the auxotrophic strain Leuconostoc mesenteroides P-60. A constant ratio of strain C3 colonies did not excrete glutamate. These colonies were subcultured, and colonial analysis of their descendants established that the change from non-excretor to excretor (Sg− → Sg+) is a spontaneous and random process with occurs at a high rate, and that an equilibrium state results from the back-transition Sg+ → Sg− in large populations. Acridine orange, ethidium bromide, and shaking have a strong influence on Sg+-to-Sg− interconversion, which suggests that a genetic element like an episome is implicated (S factor). Various auxotrophic mutants of bacterial strain C3 have been cured of the S factor. Strains lacking the S factor (S− strains) do not excrete glutamate and lose their fermentative metabolism completely. Consequently, the S factor is different from other extrachromosomal genetic factors whose elimination does not modify central metabolism. The gain of the S factor by infectious transfer has been shown with different C3 auxotrophic mutant strains. Also, the S factor has been transferred to Paracolobactrum intermedium ATCC 11606. These findings suggest that phenotypic changes observed are a consequence of elimination or infectious gain of the S factor, with its autonomous or integrated multiplication. PMID:4600693

  13. In-vitro and in-vivo antimicrobial activities of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain.

    PubMed

    Orikasa, Y; Hara, T; Miyata, A; Tamura, A; Kawaharajo, K; Matsumoto, T; Komiya, I; Iwamatsu, K; Shibahara, S; Inouye, S

    1991-01-01

    The antibacterial activity of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain, was evaluated in vitro and in vivo, with ceftazidime, aztreonam and cefoperazone as the reference antibiotics. CP6162 showed weak or little activity against Gram-positive bacteria, but potent activity against clinical isolates of the Gram-negative species including strains of Pseudomonas aeruginosa, Ps. cepacia, Acinetobacter sp., Xanthomonas maltophilia, Serratia marcescens, Enterobacter cloacae and Citrobacter freundii, which were resistant to the reference antibiotics. The MICs of CP6162 were only slightly affected by the high producers of beta-lactamases except for cephalosporinase-producing C. freundii. It was, however, affected by the presence of ferric ion. CP6162 showed in-vivo activity paralleling the in-vitro activity, and also showed pharmacokinetic parameters similar to those of ceftazidime in mice and rats.

  14. Detection of an IncA/C plasmid encoding VIM-4 and CMY-4 β-lactamases in Klebsiella oxytoca and Citrobacter koseri from an inpatient in a cardiac rehabilitation unit.

    PubMed

    Caltagirone, Mariasofia; Bitar, Ibrahim; Piazza, Aurora; Spalla, Melissa; Nucleo, Elisabetta; Navarra, Antonella; Migliavacca, Roberta

    2015-07-01

    A 62-year-old patient was transferred to the cardiac rehabilitation unit of the I.R.C.C.S. Fondazione S. Maugeri after undergoing a heart transplantation at the Acute Care Hospital I.R.C.C.S. S. Matteo of Pavia. On 1 August 2013 and during hospitalization in the rehabilitation unit, Klebsiella oxytoca and Citrobacter koseri clinical isolates were simultaneously recovered from the patient's preputial swab. Both the K. oxytoca and C. koseri strains were carbapenem- resistant by MicroScan System (Beckman Coulter). Carbapenem-resistant K. pneumoniae had previously been reported in the same rehabilitation facility. The aim of the study was to identify the carbapenem resistance mechanisms among the enterobacterial species recovered. Phenotypic screening tests useful to detect the β-lactamases/carbapenemases were performed. Carbapenem MICs were obtained by Etest. AmpC and MBL encoding genes were identified by PCR and sequencing. Conjugation assays and plasmid characterization were performed. Both of the K. oxytoca and C. koseri isolates were multi drug resistant, showing resistance to amoxicillin-clavulanic acid, three generation cephalosporins, ertapenem (K. oxytoca MIC, >32 mg/L; C. koseri MIC, 4 mg/L), imipenem (K. oxytoca MIC, 4 mg/L; C. koseri MIC, 12 mg/L), thrimethoprim sulphamethoxazole and gentamicin. Susceptibility was retained to fluoroquinolones, colistin and tigecycline. Molecular characterization confirmed the co-presence of blaCMY-4 and blaVIM-4 determinants in a 150 Kb transferable plasmid of IncA/C group. This case is the first detection in Italy of the K. oxytoca and C. koseri clinical isolates co-producing the CMY-4 and VIM-4 enzymes.

  15. Essential role of the type III secretion system effector NleB in colonization of mice by Citrobacter rodentium.

    PubMed

    Kelly, Michelle; Hart, Emily; Mundy, Rosanna; Marchès, Olivier; Wiles, Siouxsie; Badea, Luminita; Luck, Shelley; Tauschek, Marija; Frankel, Gad; Robins-Browne, Roy M; Hartland, Elizabeth L

    2006-04-01

    Attaching and effacing (A/E) pathogens are a significant cause of gastrointestinal illness in humans and animals. All A/E pathogens carry a large pathogenicity island, termed the locus for enterocyte effacement (LEE), which encodes a type III secretion system that translocates several effector proteins into host cells. To identify novel virulence determinants in A/E pathogens, we performed a signature-tagged mutagenesis screen in C57BL/6 mice by using the mouse A/E pathogen Citrobacter rodentium. Five hundred seventy-six derivatives of C. rodentium were tested in pools of 12 mutants. One attenuated mutant carried a transposon insertion in nleB, which encodes a putative effector of the LEE-encoded type III secretion system (T3SS). nleB is present in a genomic pathogenicity island that also encodes another putative effector, NleE, immediately downstream. Using translational fusions with beta-lactamase (TEM-1), we showed that both NleB and NleE were translocated into host cells by the LEE-encoded T3SS of enteropathogenic Escherichia coli. In addition, deletion of the gene encoding NleB in C. rodentium resulted in reduced colonization of mice in single infections and reduced colonic hyperplasia. In contrast, the deletion of other non-LEE-encoded effector genes in C. rodentium, nleC, nleD, or nleE, had no effect on host colonization or disease. These results suggest that nleB encodes an important virulence determinant of A/E pathogens.

  16. Absence of PmrAB-Mediated Phosphoethanolamine Modifications of Citrobacter rodentium Lipopolysaccharide Affects Outer Membrane Integrity▿†

    PubMed Central

    Viau, Charles; Le Sage, Valerie; Ting, Daniel K.; Gross, Jeremy; Le Moual, Hervé

    2011-01-01

    The PmrAB two-component system of enterobacteria regulates a number of genes whose protein products modify lipopolysaccharide (LPS). The LPS is modified during transport to the bacterial outer membrane (OM). A subset of PmrAB-mediated LPS modifications consists of the addition of phosphoethanolamine (pEtN) to lipid A by PmrC and to the core by CptA. In Salmonella enterica, pEtN modifications have been associated with resistance to polymyxin B and to excess iron. To investigate putative functions of pEtN modifications in Citrobacter rodentium, ΔpmrAB, ΔpmrC, ΔcptA, and ΔpmrC ΔcptA deletion mutants were constructed. Compared to the wild type, most mutant strains were found to be more susceptible to antibiotics that must diffuse across the LPS layer of the OM. All mutant strains also showed increased influx rates of ethidium dye across their OM, suggesting that PmrAB-regulated pEtN modifications affect OM permeability. This was confirmed by increased partitioning of the fluorescent dye 1-N-phenylnaphthylamine (NPN) into the OM phospholipid layer of the mutant strains. In addition, substantial release of periplasmic β-lactamase was observed for the ΔpmrAB and ΔpmrC ΔcptA strains, indicating a loss of OM integrity. This study attributes a new role for PmrAB-mediated pEtN LPS modifications in the maintenance of C. rodentium OM integrity. PMID:21378194

  17. Cadmium accumulation by a Citrobacter sp. immobilized on gel and solid supports: applicability to the treatment of liquid wastes containing heavy metal cations

    SciTech Connect

    Macaskie, L.E.; Wates, J.M.; Dean, A.C.R.

    1987-01-01

    Polyacrylamide gel-immobilized cells of a Citrobacter sp. removed cadmium from flows supplemented with glycerol 2-phosphate, the metal uptake mechanism being mediated by the activity of a cell-bound phosphatase that precipitates liberated inorganic phosphate with heavy metals at the cell surface. The constraints of elevated flow rate and temperature were investigated and the results discussed in terms of the kinetics of immobilized enzymes. Loss in activity with respect to cadmium accumulation but not inorganic phosphate liberation was observed at acid pH and was attributed to the pH-dependent solubility of cadmium phosphate. Similarly high concentrations of chloride ions, and traces of cyanide inhibited cadmium uptake and this was attributed to the ability of these anions to complex heavy metals, especially the ability of CN/sup -/ to form complex anions with Cd/sup 2 +/. The data are discussed in terms of the known chemistry of chloride and cyanide-cadmium complexes and the relevance of these factors in the treatment of metal-containing liquid wastes is discussed. The cells immobilized in polyacrylamide provided a convenient small-scale laboratory model system. It was found that the Citrobacter sp. could be immobilized on glass supports with no chemical treatment or modification necessary. Such cells were also effective in metal accumulation and a prototype system more applicable to the treatment of metal-containing streams on a larger scale is described.

  18. Genome-Wide Analysis of the Pho Regulon in a pstCA Mutant of Citrobacter rodentium

    PubMed Central

    Cheng, Catherine; Wakefield, Matthew J.; Yang, Ji; Tauschek, Marija; Robins-Browne, Roy M.

    2012-01-01

    The phosphate-specific transport operon, pstSCAB-phoU, of Gram-negative bacteria is an essential part of the Pho regulon. Its key roles are to encode a high-affinity inorganic phosphate transport system and to prevent activation of PhoB in phosphate-rich environments. In general, mutations in pstSCAB-phoU lead to the constitutive expression of the Pho regulon. Previously, we constructed a pstCA deletion mutant of Citrobacter rodentium and found it to be attenuated for virulence in mice, its natural host. This attenuation was dependent on PhoB or PhoB-regulated gene(s) because a phoB mutation restored virulence for mice to the pstCA mutant. To investigate how downstream genes may contribute to the virulence of C. rodentium, we used microarray analysis to investigate global gene expression of C. rodentium strain ICC169 and its isogenic pstCA mutant when grown in phosphate-rich medium. Overall 323 genes of the pstCA mutant were differentially expressed by at least 1.5-fold compared to the wild-type C. rodentium. Of these 145 were up-regulated and 178 were down-regulated. Differentially expressed genes included some involved in phosphate homoeostasis, cellular metabolism and protein metabolism. A large number of genes involved in stress responses and of unknown function were also differentially expressed, as were some virulence-associated genes. Up-regulated virulence-associated genes in the pstCA mutant included that for DegP, a serine protease, which appeared to be directly regulated by PhoB. Down-regulated genes included those for the production of the urease, flagella, NleG8 (a type III-secreted protein) and the tad focus (which encodes type IVb pili in Yersinia enterocolitica). Infection studies using C57/BL6 mice showed that DegP and NleG8 play a role in bacterial virulence. Overall, our study provides evidence that Pho is a global regulator of gene expression in C. rodentium and indicates the presence of at least two previously unrecognized virulence

  19. Interleukin-7 produced by intestinal epithelial cells in response to Citrobacter rodentium infection plays a major role in innate immunity against this pathogen.

    PubMed

    Zhang, Wei; Du, Jiang-Yuan; Yu, Qing; Jin, Jun-O

    2015-08-01

    Interleukin-7 (IL-7) engages multiple mechanisms to overcome chronic viral infections, but the role of IL-7 in bacterial infections, especially enteric bacterial infections, remains unclear. Here we characterized the previously unexplored role of IL-7 in the innate immune response to the attaching and effacing bacterium Citrobacter rodentium. C. rodentium infection induced IL-7 production from intestinal epithelial cells (IECs). IL-7 production from IECs in response to C. rodentium was dependent on gamma interferon (IFN-γ)-producing NK1.1(+) cells and IL-12. Treatment with anti-IL-7Rα antibody during C. rodentium infection resulted in a higher bacterial burden, enhanced intestinal damage, and greater weight loss and mortality than observed with the control IgG treatment. IEC-produced IL-7 was only essential for protective immunity against C. rodentium during the first 6 days after infection. An impaired bacterial clearance upon IL-7Rα blockade was associated with a significant decrease in macrophage accumulation and activation in the colon. Moreover, C. rodentium-induced expansion and activation of intestinal CD4(+) lymphoid tissue inducer (LTi) cells was completely abrogated by IL-7Rα blockade. Collectively, these data demonstrate that IL-7 is produced by IECs in response to C. rodentium infection and plays a critical role in the protective immunity against this intestinal attaching and effacing bacterium.

  20. A C-terminal class I PDZ binding motif of EspI/NleA modulates the virulence of attaching and effacing Escherichia coli and Citrobacter rodentium.

    PubMed

    Lee, Sau Fung; Kelly, Michelle; McAlister, Adrian; Luck, Shelley N; Garcia, Erin L; Hall, Randy A; Robins-Browne, Roy M; Frankel, Gad; Hartland, Elizabeth L

    2008-02-01

    Enteropathogenic Escherichia coli induces characteristic attaching-effacing (A/E) lesions on the intestinal mucosa during infection. The locus of enterocyte effacement is essential for A/E lesion formation and encodes a type III secretion system that translocates multiple effector proteins into the host cell. Following translocation, EspI/NleA localizes to the Golgi. Using the yeast two-hybrid system (Y2HS) and PSD-95/Disk-large/ZO-1 (PDZ)-domain protein array overlays, we identified 15 putative host-interacting partners of EspI. All but two of the target proteins contained PDZ domains. Examination of the EspI amino acid sequence revealed a C-terminal consensus class I PDZ binding motif. Deletion of the last 7 amino acids of EspI to generate EspI(DeltaC7) abrogated the Y2HS interaction between EspI and 5 of the 6 putative host cell target proteins tested. Deletion of the EspI PDZ binding motif also resulted in delayed trafficking of EspI to the Golgi. Using a mouse model of infection, we showed that Citrobacter rodentium expressing truncated EspI(DeltaC7) was attenuated when in competition with C. rodentium expressing full-length EspI. Overall, these results suggested that EspI may modulate the virulence of A/E pathogens by binding host PDZ-domain proteins.

  1. Analysis of relationships among isolates of Citrobacter diversus by using DNA fingerprints generated by repetitive sequence-based primers in the polymerase chain reaction.

    PubMed Central

    Woods, C R; Versalovic, J; Koeuth, T; Lupski, J R

    1992-01-01

    Oligonucleotide probes which match consensus sequences of the repetitive extragenic palindromic (REP) element hybridize to genomic DNA of diverse bacterial species. Primers based on the REP sequence generate complex band patterns with genomic DNA in the polymerase chain reaction (PCR), a technique named REP-PCR. We used REP-PCR with genomic DNA to fingerprint 47 isolates of Citrobacter diversus. Previously, 37 were assigned electrophoretic types (ETs) by multilocus enzyme electrophoresis and 35 were evaluated by using outer membrane protein profiles. Fingerprints were compared by visual inspection and by similarity coefficients (SimCs) based on the number of common bands versus total bands between two given isolates. DNA fingerprints were highly similar visually for patient pairs and outbreak-related sets. SimCs for these were > or = 0.952. Fingerprints of isolates with different ETs generally were distinctive. Among 21 unrelated isolates representing 15 ETs, only 6 of 210 comparisons had SimCs of > or = 0.952. REP-PCR rapidly generated DNA fingerprints which were highly similar for epidemiologically linked isolates of C. diversus and distinct for previously characterized strains within this species. The ability of this method to discriminate between C. diversus isolates with the same biotype was similar to that of multilocus enzyme electrophoresis and outer membrane protein profiles. REP-PCR may be useful in evaluation of apparent outbreaks of this or other bacterial species which possess these extragenic, repetitive elements. Images PMID:1452663

  2. IL-4 Protects the Mitochondria Against TNFα and IFNγ Induced Insult During Clearance of Infection with Citrobacter rodentium and Escherichia coli

    PubMed Central

    Maiti, Arpan K.; Sharba, Sinan; Navabi, Nazanin; Forsman, Huamei; Fernandez, Harvey R.; Lindén, Sara K.

    2015-01-01

    Citrobacter rodentium is a murine pathogen that serves as a model for enteropathogenic Escherichia coli. C. rodentium infection reduced the quantity and activity of mitochondrial respiratory complexes I and IV, as well as phosphorylation capacity, mitochondrial transmembrane potential and ATP generation at day 10, 14 and 19 post infection. Cytokine mRNA quantification showed increased levels of IFNγ, TNFα, IL-4, IL-6, and IL-12 during infection. The effects of adding these cytokines, C. rodentium and E. coli were hence elucidated using an in vitro colonic mucosa. Both infection and TNFα, individually and combined with IFNγ, decreased complex I and IV enzyme levels and mitochondrial function. However, IL-4 reversed these effects, and IL-6 protected against loss of complex IV. Both in vivo and in vitro, the dysfunction appeared caused by nitric oxide-generation, and was alleviated by an antioxidant targeting mitochondria. IFNγ −/− mice, containing a similar pathogen burden but higher IL-4 and IL-6, displayed no loss of any of the four complexes. Thus, the cytokine environment appears to be a more important determinant of mitochondrial function than direct actions of the pathogen. As IFNγ and TNFα levels increase during clearance of infection, the concomitant increase in IL-4 and IL-6 protects mitochondrial function. PMID:26481427

  3. IL-4 Protects the Mitochondria Against TNFα and IFNγ Induced Insult During Clearance of Infection with Citrobacter rodentium and Escherichia coli.

    PubMed

    Maiti, Arpan K; Sharba, Sinan; Navabi, Nazanin; Forsman, Huamei; Fernandez, Harvey R; Lindén, Sara K

    2015-01-01

    Citrobacter rodentium is a murine pathogen that serves as a model for enteropathogenic Escherichia coli. C. rodentium infection reduced the quantity and activity of mitochondrial respiratory complexes I and IV, as well as phosphorylation capacity, mitochondrial transmembrane potential and ATP generation at day 10, 14 and 19 post infection. Cytokine mRNA quantification showed increased levels of IFNγ, TNFα, IL-4, IL-6, and IL-12 during infection. The effects of adding these cytokines, C. rodentium and E. coli were hence elucidated using an in vitro colonic mucosa. Both infection and TNFα, individually and combined with IFNγ, decreased complex I and IV enzyme levels and mitochondrial function. However, IL-4 reversed these effects, and IL-6 protected against loss of complex IV. Both in vivo and in vitro, the dysfunction appeared caused by nitric oxide-generation, and was alleviated by an antioxidant targeting mitochondria. IFNγ -/- mice, containing a similar pathogen burden but higher IL-4 and IL-6, displayed no loss of any of the four complexes. Thus, the cytokine environment appears to be a more important determinant of mitochondrial function than direct actions of the pathogen. As IFNγ and TNFα levels increase during clearance of infection, the concomitant increase in IL-4 and IL-6 protects mitochondrial function.

  4. Effect of surfactant-induced cell surface modifications on electron transport system and catechol 1,2-dioxygenase activities and phenanthrene biodegradation by Citrobacter sp. SA01.

    PubMed

    Li, Feng; Zhu, Lizhong

    2012-11-01

    In order to better understand how surfactants affect biodegradation of hydrophobic organic compounds (HOCs), Tween 80 and sodium dodecyl benzene sulfonate (SDBS), were selected to investigate effects on cell surface hydrophobicity (CSH), electron transport system (ETS) activities and phenanthrene biodegradation by Citrobacter sp. SA01. Tween 80 and SDBS increased CSH by 19.8-25.2%, ETS activities by 352.1-376.0μmol/gmin, catechol 1,2-dioxygenase (C12) activities by 50.8-52.7U/L, and phenanthrene biodegradation by 8.9-17.2% separately in the presence of 50mg/L of surfactants as compared to in their absence. Lipopolysaccharide (LPS) release was 334.7μg/mg in the presence of both surfactants whereas in their absence only 8.6-44.4μg/mg of LPS was released. Thus, enhanced LPS release probably increased ETS and C12 activities as well as phenanthrene biodegradation by increasing CSH. The results demonstrate that surfactant-enhanced CSH provides a simple, yet effective strategy for field applications of surfactant-enhanced bioremediation of HOCs.

  5. Citrobacter amalonaticus phytase on the cell surface of Pichia pastoris exhibits high pH stability as a promising potential feed supplement.

    PubMed

    Li, Cheng; Lin, Ying; Huang, Yuanyuan; Liu, Xiaoxiao; Liang, Shuli

    2014-01-01

    Phytase expressed and anchored on the cell surface of Pichia pastoris avoids the expensive and time-consuming steps of protein purification and separation. Furthermore, yeast cells with anchored phytase can be used as a whole-cell biocatalyst. In this study, the phytase gene of Citrobacter amalonaticus was fused with the Pichia pastoris glycosylphosphatidylinositol (GPI)-anchored glycoprotein homologue GCW61. Phytase exposed on the cell surface exhibits a high activity of 6413.5 U/g, with an optimal temperature of 60°C. In contrast to secreted phytase, which has an optimal pH of 5.0, phytase presented on the cell surface is characterized by an optimal pH of 3.0. Moreover, our data demonstrate that phytase anchored on the cell surface exhibits higher pH stability than its secreted counterpart. Interestingly, our in vitro digestion experiments demonstrate that phytase attached to the cell surface is a more efficient enzyme than secreted phytase.

  6. Transcriptional frameshifting rescues Citrobacter rodentium type VI secretion by the production of two length variants from the prematurely interrupted tssM gene.

    PubMed

    Gueguen, Erwan; Wills, Norma M; Atkins, John F; Cascales, Eric

    2014-12-01

    The Type VI secretion system (T6SS) mediates toxin delivery into both eukaryotic and prokaryotic cells. It is composed of a cytoplasmic structure resembling the tail of contractile bacteriophages anchored to the cell envelope through a membrane complex composed of the TssL and TssM inner membrane proteins and of the TssJ outer membrane lipoprotein. The C-terminal domain of TssM is required for its interaction with TssJ, and for the function of the T6SS. In Citrobacter rodentium, the tssM1 gene does not encode the C-terminal domain. However, the stop codon is preceded by a run of 11 consecutive adenosines. In this study, we demonstrate that this poly-A tract is a transcriptional slippery site that induces the incorporation of additional adenosines, leading to frameshifting, and hence the production of two TssM1 variants, including a full-length canonical protein. We show that both forms of TssM1, and the ratio between these two forms, are required for the function of the T6SS in C. rodentium. Finally, we demonstrate that the tssM gene associated with the Yersinia pseudotuberculosis T6SS-3 gene cluster is also subjected to transcriptional frameshifting.

  7. Genomic Insights into a New Citrobacter koseri Strain Revealed Gene Exchanges with the Virulence-Associated Yersinia pestis pPCP1 Plasmid.

    PubMed

    Armougom, Fabrice; Bitam, Idir; Croce, Olivier; Merhej, Vicky; Barassi, Lina; Nguyen, Ti-Thien; La Scola, Bernard; Raoult, Didier

    2016-01-01

    The history of infectious diseases raised the plague as one of the most devastating for human beings. Far too often considered an ancient disease, the frequent resurgence of the plague has led to consider it as a reemerging disease in Madagascar, Algeria, Libya, and Congo. The genetic factors associated with the pathogenicity of Yersinia pestis, the causative agent of the plague, involve the acquisition of the pPCP1 plasmid that promotes host invasion through the expression of the virulence factor Pla. The surveillance of plague foci after the 2003 outbreak in Algeria resulted in a positive detection of the specific pla gene of Y. pestis in rodents. However, the phenotypic characterization of the isolate identified a Citrobacter koseri. The comparative genomics of our sequenced C. koseri URMITE genome revealed a mosaic gene structure resulting from the lifestyle of our isolate and provided evidence for gene exchanges with different enteric bacteria. The most striking was the acquisition of a continuous 2 kb genomic fragment containing the virulence factor Pla of the Y. pestis pPCP1 plasmid; however, the subcutaneous injection of the CKU strain in mice did not produce any pathogenic effect. Our findings demonstrate that fast molecular detection of plague using solely the pla gene is unsuitable and should rather require Y. pestis gene marker combinations. We also suggest that the evolutionary force that might govern the expression of pathogenicity can occur through the acquisition of virulence genes but could also require the loss or the inactivation of resident genes such as antivirulence genes. PMID:27014253

  8. RegA, an AraC-like protein, is a global transcriptional regulator that controls virulence gene expression in Citrobacter rodentium.

    PubMed

    Hart, Emily; Yang, Ji; Tauschek, Marija; Kelly, Michelle; Wakefield, Matthew J; Frankel, Gad; Hartland, Elizabeth L; Robins-Browne, Roy M

    2008-11-01

    Citrobacter rodentium is an attaching and effacing pathogen which causes transmissible colonic hyperplasia in mice. Infection with C. rodentium serves as a model for infection of humans with enteropathogenic and enterohemorrhagic Escherichia coli. To identify novel colonization factors of C. rodentium, we screened a signature-tagged mutant library of C. rodentium in mice. One noncolonizing mutant had a single transposon insertion in an open reading frame (ORF) which we designated regA because of its homology to genes encoding members of the AraC family of transcriptional regulators. Deletion of regA in C. rodentium resulted in markedly reduced colonization of the mouse intestine. Examination of lacZ transcriptional fusions using promoter regions of known and putative virulence-associated genes of C. rodentium revealed that RegA strongly stimulated transcription of two newly identified genes located close to regA, which we designated adcA and kfcC. The cloned adcA gene conferred autoaggregation and adherence to mammalian cells to E. coli strain DH5alpha, and a kfc mutation led to a reduction in the duration of intestinal colonization, but the kfc mutant was far less attenuated than the regA mutant. These results indicated that other genes of C. rodentium whose expression required activation by RegA were required for colonization. Microarray analysis revealed a number of RegA-regulated ORFs encoding proteins homologous to known colonization factors. Transcription of these putative virulence determinants was activated by RegA only in the presence of sodium bicarbonate. Taken together, these results show that RegA is a global regulator of virulence in C. rodentium which activates factors that are required for intestinal colonization.

  9. The in vitro and in vivo effects of constitutive light expression on a bioluminescent strain of the mouse enteropathogen Citrobacter rodentium

    PubMed Central

    Read, Hannah M.; Mills, Grant; Johnson, Sarah; Tsai, Peter; Dalton, James; Barquist, Lars; Print, Cristin G.; Patrick, Wayne M.

    2016-01-01

    Bioluminescent reporter genes, such as those from fireflies and bacteria, let researchers use light production as a non-invasive and non-destructive surrogate measure of microbial numbers in a wide variety of environments. As bioluminescence needs microbial metabolites, tagging microorganisms with luciferases means only live metabolically active cells are detected. Despite the wide use of bioluminescent reporter genes, very little is known about the impact of continuous (also called constitutive) light expression on tagged bacteria. We have previously made a bioluminescent strain of Citrobacter rodentium, a bacterium which infects laboratory mice in a similar way to how enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) infect humans. In this study, we compared the growth of the bioluminescent C. rodentium strain ICC180 with its non-bioluminescent parent (strain ICC169) in a wide variety of environments. To understand more about the metabolic burden of expressing light, we also compared the growth profiles of the two strains under approximately 2,000 different conditions. We found that constitutive light expression in ICC180 was near-neutral in almost every non-toxic environment tested. However, we also found that the non-bioluminescent parent strain has a competitive advantage over ICC180 during infection of adult mice, although this was not enough for ICC180 to be completely outcompeted. In conclusion, our data suggest that constitutive light expression is not metabolically costly to C. rodentium and supports the view that bioluminescent versions of microbes can be used as a substitute for their non-bioluminescent parents to study bacterial behaviour in a wide variety of environments. PMID:27366640

  10. The in vitro and in vivo effects of constitutive light expression on a bioluminescent strain of the mouse enteropathogen Citrobacter rodentium.

    PubMed

    Read, Hannah M; Mills, Grant; Johnson, Sarah; Tsai, Peter; Dalton, James; Barquist, Lars; Print, Cristin G; Patrick, Wayne M; Wiles, Siouxsie

    2016-01-01

    Bioluminescent reporter genes, such as those from fireflies and bacteria, let researchers use light production as a non-invasive and non-destructive surrogate measure of microbial numbers in a wide variety of environments. As bioluminescence needs microbial metabolites, tagging microorganisms with luciferases means only live metabolically active cells are detected. Despite the wide use of bioluminescent reporter genes, very little is known about the impact of continuous (also called constitutive) light expression on tagged bacteria. We have previously made a bioluminescent strain of Citrobacter rodentium, a bacterium which infects laboratory mice in a similar way to how enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) infect humans. In this study, we compared the growth of the bioluminescent C. rodentium strain ICC180 with its non-bioluminescent parent (strain ICC169) in a wide variety of environments. To understand more about the metabolic burden of expressing light, we also compared the growth profiles of the two strains under approximately 2,000 different conditions. We found that constitutive light expression in ICC180 was near-neutral in almost every non-toxic environment tested. However, we also found that the non-bioluminescent parent strain has a competitive advantage over ICC180 during infection of adult mice, although this was not enough for ICC180 to be completely outcompeted. In conclusion, our data suggest that constitutive light expression is not metabolically costly to C. rodentium and supports the view that bioluminescent versions of microbes can be used as a substitute for their non-bioluminescent parents to study bacterial behaviour in a wide variety of environments. PMID:27366640

  11. Enzymically mediated bioprecipitation of uranium by a Citrobacter sp. : a concerted role for exocellular lipopolysaccharide and associated phosphatase in biomineral formation.

    PubMed

    Macaskie, L E; Bonthrone, K M; Yong, P; Goddard, D T

    2000-08-01

    A Citrobacter sp. accumulated uranyl ion (UO2(2+)) via precipitation with phosphate ligand liberated by phosphatase activity. The onset and rate of uranyl phosphate deposition were promoted by NH4(+), forming NH(4)UO(2)PO(4), which has a lower solubility product than NaUO(2)PO(4). This acceleration decoupled the rate-limiting chemical crystallization process from the biochemical phosphate ligand generation. This provided a novel approach to monitor the cell-surface-associated changes using atomic-force microscopy in conjunction with transmission electron microscopy and electron-probe X-ray microanalysis, to visualize deposition of uranyl phosphate at the cell surface. Analysis of extracted surface materials by (31)P NMR spectroscopy showed phosphorus resonances at chemical shifts of 0.3 and 2.0 p.p.m., consistent with monophosphate groups of the lipid A backbone of the lipopolysaccharide (LPS). Addition of fUO2(2+) to the extract gave a yellow precipitate which contained uranyl phosphate, while addition of Cd(2+) gave a chemical shift of both resonances to a single new resonance at 3 p.p.m. Acid-phosphatase-mediated crystal growth exocellularly was suggested by the presence of acid phosphatase, localized by immunogold labelling, on the outer membrane and on material exuded from the cells. Metal deposition is proposed to occur via an initial nucleation with phosphate groups localized within the LPS, shown by other workers to be produced exocellularly in association with phosphatase. The crystals are further consolidated with additional, enzymically generated phosphate in close juxtaposition, giving high loads of LPS-bound uranyl phosphate without loss of activity and distinguishing this from simple biosorption, or periplasmic or cellular metal accumulation mechanisms. Accumulation of 'tethered' metal phosphate within the LPS is suggested to prevent fouling of the cell surface by the accumulated precipitate and localization of phosphatase exocellularly is consistent

  12. Genomic Insights into a New Citrobacter koseri Strain Revealed Gene Exchanges with the Virulence-Associated Yersinia pestis pPCP1 Plasmid

    PubMed Central

    Armougom, Fabrice; Bitam, Idir; Croce, Olivier; Merhej, Vicky; Barassi, Lina; Nguyen, Ti-Thien; La Scola, Bernard; Raoult, Didier

    2016-01-01

    The history of infectious diseases raised the plague as one of the most devastating for human beings. Far too often considered an ancient disease, the frequent resurgence of the plague has led to consider it as a reemerging disease in Madagascar, Algeria, Libya, and Congo. The genetic factors associated with the pathogenicity of Yersinia pestis, the causative agent of the plague, involve the acquisition of the pPCP1 plasmid that promotes host invasion through the expression of the virulence factor Pla. The surveillance of plague foci after the 2003 outbreak in Algeria resulted in a positive detection of the specific pla gene of Y. pestis in rodents. However, the phenotypic characterization of the isolate identified a Citrobacter koseri. The comparative genomics of our sequenced C. koseri URMITE genome revealed a mosaic gene structure resulting from the lifestyle of our isolate and provided evidence for gene exchanges with different enteric bacteria. The most striking was the acquisition of a continuous 2 kb genomic fragment containing the virulence factor Pla of the Y. pestis pPCP1 plasmid; however, the subcutaneous injection of the CKU strain in mice did not produce any pathogenic effect. Our findings demonstrate that fast molecular detection of plague using solely the pla gene is unsuitable and should rather require Y. pestis gene marker combinations. We also suggest that the evolutionary force that might govern the expression of pathogenicity can occur through the acquisition of virulence genes but could also require the loss or the inactivation of resident genes such as antivirulence genes. PMID:27014253

  13. Activation of Plasmacytoid Dendritic Cells in Colon-Draining Lymph Nodes during Citrobacter rodentium Infection Involves Pathogen-Sensing and Inflammatory Pathways Distinct from Conventional Dendritic Cells.

    PubMed

    Toivonen, Raine; Kong, Lingjia; Rasool, Omid; Lund, Riikka J; Lahesmaa, Riitta; Hänninen, Arno

    2016-06-01

    Dendritic cells (DCs) bear the main responsibility for initiation of adaptive immune responses necessary for antimicrobial immunity. In the small intestine, afferent lymphatics convey Ags and microbial signals to mesenteric lymph nodes (LNs) to induce adaptive immune responses against microbes and food Ags derived from the small intestine. Whether the large intestine is covered by the same lymphatic system or represents its own lymphoid compartment has not been studied until very recently. We identified three small mesenteric LNs, distinct from small intestinal LNs, which drain lymph specifically from the colon, and studied DC responses to the attaching and effacing pathogen Citrobacter rodentium in these. Transcriptional profiling of conventional (CD11c(high)CD103(high)) DC and plasmacytoid (plasmacytoid DC Ag-1(high)B220(+)CD11c(int)) DC (pDC) populations during steady-state conditions revealed activity of distinct sets of genes in these two DC subsets, both in small intestinal and colon-draining LNs. C. rodentium activated DC especially in colon-draining LNs, and gene expression changed in pDC more profoundly than in conventional DC. Among the genes most upregulated in pDC were C-type lectin receptor CLEC4E, IL-1Rs (IL-1R1 and -2), proinflammatory cytokines (IL-1a and IL-6), and TLR6. Our results indicate that colon immune surveillance is distinct from that of the small intestine in terms of draining LNs, and identify pDC as active sentinels of colonic inflammation and/or microbial dysbiosis. PMID:27183629

  14. Screening of bacterial isolates for mannose-specific lectin activity by agglutination of yeasts.

    PubMed Central

    Mirelman, D; Altmann, G; Eshdat, Y

    1980-01-01

    A total of 393 clinical bacterial isolates were tested for their ability to agglutinate yeast cells of either Saccharomyces cerevisiae or Candida albicans. A positive agglutination of yeasts that could be prevented by methyl alpha-D-mannoside was taken as an indication for the possible presence of a mannose-specific lectin (carbohydrate-binding protein) on the surface of the tested bacteria. Agglutination tests on glass slides showed that 38% of all the isolates tested were positive in their capacity to agglutinate yeasts. Among the various strains tested, all isolates of Serratia marcescens, Proteus morganii, and Citrobacter diversus, as well as 94% of Klebsiella pneumoniae, were positive. On the other hand, only 46% of the Escherichia coli, 48% of the salmonellae, 44% of the Citrobacter freundii, and 71% of the Aeromonas hydrophila isolates were positive. A quantitative determination of the lectin activity done by observing the agglutination of yeasts in microtiter plates showed that S. marcescens isolates were the most avid binders to the yeast, whereas Klebsiella and Citrobacter isolates were the weakest. PMID:6989854

  15. Chemical composition and antibacterial activity of Lavandula coronopifolia essential oil against antibiotic-resistant bacteria.

    PubMed

    Ait Said, L; Zahlane, K; Ghalbane, I; El Messoussi, S; Romane, A; Cavaleiro, C; Salgueiro, L

    2015-01-01

    The aim of this study was to analyse the composition of the essential oil (EO) of Lavandula coronopifolia from Morocco and to evaluate its in vitro antibacterial activity against antibiotic-resistant bacteria isolated from clinical infections. The antimicrobial activity was assessed by a broth micro-well dilution method using multiresistant clinical isolates of 11 pathogenic bacteria: Klebsiella pneumoniae subsp. pneumoniae, Klebsiella ornithinolytica, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Providencia rettgeri, Citrobacter freundii, Hafnia alvei, Salmonella spp., Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus. The main compounds of the oil were carvacrol (48.9%), E-caryophyllene (10.8%) and caryophyllene oxide (7.7%). The oil showed activity against all tested strains with minimal inhibitory concentration (MIC) values ranging between 1% and 4%. For most of the strains, the MIC value was equivalent to the minimal bactericidal concentration value, indicating a clear bactericidal effect of L. coronopifolia EO. PMID:25174508

  16. R-Spondins Are Expressed by the Intestinal Stroma and are Differentially Regulated during Citrobacter rodentium- and DSS-Induced Colitis in Mice

    PubMed Central

    Kang, Eugene; Yousefi, Mitra; Gruenheid, Samantha

    2016-01-01

    The R-spondin family of proteins has recently been described as secreted enhancers of β-catenin activation through the canonical Wnt signaling pathway. We previously reported that Rspo2 is a major determinant of susceptibility to Citrobacter rodentium-mediated colitis in mice and recent genome-wide association studies have revealed RSPO3 as a candidate Crohn’s disease-specific inflammatory bowel disease susceptibility gene in humans. However, there is little information on the endogenous expression and cellular source of R-spondins in the colon at steady state and during intestinal inflammation. RNA sequencing and qRT-PCR were used to assess the expression of R-spondins at steady state and in two mouse models of colonic inflammation. The cellular source of R-spondins was assessed in specific colonic cell populations isolated by cell sorting. Data mining from publicly available datasets was used to assess the expression of R-spondins in the human colon. At steady state, colonic expression of R-spondins was found to be exclusive to non-epithelial CD45- lamina propria cells, and Rspo3/RSPO3 was the most highly expressed R-spondin in both mouse and human colon. R-spondin expression was found to be highly dynamic and differentially regulated during C. rodentium infection and dextran sodium sulfate (DSS) colitis, with notably high levels of Rspo3 expression during DSS colitis, and high levels of Rspo2 expression during C. rodentium infection, specifically in susceptible mice. Our data are consistent with the hypothesis that in the colon, R-spondins are expressed by subepithelial stromal cells, and that Rspo3/RSPO3 is the family member most implicated in colonic homeostasis. The differential regulation of the R-spondins in different models of intestinal inflammation indicate they respond to specific pathogenic and inflammatory signals that differ in the two models and provides further evidence that this family of proteins plays a key role in linking intestinal

  17. R-Spondins Are Expressed by the Intestinal Stroma and are Differentially Regulated during Citrobacter rodentium- and DSS-Induced Colitis in Mice.

    PubMed

    Kang, Eugene; Yousefi, Mitra; Gruenheid, Samantha

    2016-01-01

    The R-spondin family of proteins has recently been described as secreted enhancers of β-catenin activation through the canonical Wnt signaling pathway. We previously reported that Rspo2 is a major determinant of susceptibility to Citrobacter rodentium-mediated colitis in mice and recent genome-wide association studies have revealed RSPO3 as a candidate Crohn's disease-specific inflammatory bowel disease susceptibility gene in humans. However, there is little information on the endogenous expression and cellular source of R-spondins in the colon at steady state and during intestinal inflammation. RNA sequencing and qRT-PCR were used to assess the expression of R-spondins at steady state and in two mouse models of colonic inflammation. The cellular source of R-spondins was assessed in specific colonic cell populations isolated by cell sorting. Data mining from publicly available datasets was used to assess the expression of R-spondins in the human colon. At steady state, colonic expression of R-spondins was found to be exclusive to non-epithelial CD45- lamina propria cells, and Rspo3/RSPO3 was the most highly expressed R-spondin in both mouse and human colon. R-spondin expression was found to be highly dynamic and differentially regulated during C. rodentium infection and dextran sodium sulfate (DSS) colitis, with notably high levels of Rspo3 expression during DSS colitis, and high levels of Rspo2 expression during C. rodentium infection, specifically in susceptible mice. Our data are consistent with the hypothesis that in the colon, R-spondins are expressed by subepithelial stromal cells, and that Rspo3/RSPO3 is the family member most implicated in colonic homeostasis. The differential regulation of the R-spondins in different models of intestinal inflammation indicate they respond to specific pathogenic and inflammatory signals that differ in the two models and provides further evidence that this family of proteins plays a key role in linking intestinal

  18. Transfer of amikacin resistance by closely related plasmids in members of the family Enterobacteriaceae isolated in Chile.

    PubMed Central

    Van Nhieu, G T; Goldstein, F W; Pinto, M E; Acar, J F; Collatz, E

    1986-01-01

    During a 9-month period when amikacin was the sole aminoglycoside used clinically in a hospital in Santiago, Chile, resistance to amikacin and other antibiotics was encountered in 42 strains of the family Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, and Serratia liquefaciens. Amikacin resistance was transferable by conjugation and carried by IncM plasmids ranging in size from ca. 48.4 to 58.1 kilobase pairs. The plasmids had ca. 70 to 80% of their structure in common, as judged after digestion with restriction endonucleases. The resistance was mediated by a 6' aminoglycoside acetyltransferase. We conclude that selective pressure has favored the dissemination of a wide-host-range amikacin resistance plasmid and its derivatives. Images PMID:3015007

  19. Mass mortality in ornamental fish, Cyprinus carpio koi caused by a bacterial pathogen, Proteus hauseri.

    PubMed

    Kumar, Raj; Swaminathan, T Raja; Kumar, Rahul G; Dharmaratnam, Arathi; Basheer, V S; Jena, J K

    2015-09-01

    Moribund koi carp, Cyprinus carpio koi, from a farm with 50% cumulative mortality were sampled with the aim of isolating and detecting the causative agent. Three bacterial species viz., Citrobacter freundii (NSCF-1), Klebsiella pneumoniae (NSKP-1) and Proteus hauseri [genomospecies 3 of Proteus vulgaris Bio group 3] (NSPH-1) were isolated, identified and characterized on the basis of biochemical tests and sequencing of the 16S rDNA gene using universal bacterial primers. Challenge experiments with these isolates using healthy koi carp showed that P. hauseri induced identical clinical and pathological states within 3 d of intramuscular injection. The results suggest P. hauseri (NSPH-1) was the causative agent. In phylogenetic analysis, strain NSPH-1 formed a distinct cluster with other P. hauseri reference strains with ≥99% sequence similarity. P. hauseri isolates were found sensitive to Ampicillin, Cefalexin, Ciprofloxacin and Cefixime and resistant to Gentamycin, Oxytetracycline, Chloramphenicol, and Kanamycin. The affected fish recovered from the infection after ciprofloxacin treatment.

  20. First Identification of Pseudomonas aeruginosa Isolates Producing a KPC-Type Carbapenem-Hydrolyzing β-Lactamase▿

    PubMed Central

    Villegas, Maria Virginia; Lolans, Karen; Correa, Adriana; Kattan, Juan Nicolas; Lopez, Jaime A.; Quinn, John P.

    2007-01-01

    In Medellin, Colombia, three Pseudomonas aeruginosa isolates with high-level carbapenem resistance (MIC ≥ 256 μg/ml) and an isolate of Citrobacter freundii with reduced susceptibility to imipenem produced the plasmid-mediated class A carbapenemase KPC-2. This is the first report of a KPC-type β-lactamase identified outside of the family Enterobacteriaceae. PMID:17261621

  1. Single-molecule sequencing to track plasmid diversity of hospital-associated carbapenemase-producing Enterobacteriaceae.

    PubMed

    Conlan, Sean; Thomas, Pamela J; Deming, Clayton; Park, Morgan; Lau, Anna F; Dekker, John P; Snitkin, Evan S; Clark, Tyson A; Luong, Khai; Song, Yi; Tsai, Yu-Chih; Boitano, Matthew; Dayal, Jyoti; Brooks, Shelise Y; Schmidt, Brian; Young, Alice C; Thomas, James W; Bouffard, Gerard G; Blakesley, Robert W; Mullikin, James C; Korlach, Jonas; Henderson, David K; Frank, Karen M; Palmore, Tara N; Segre, Julia A

    2014-09-17

    Public health officials have raised concerns that plasmid transfer between Enterobacteriaceae species may spread resistance to carbapenems, an antibiotic class of last resort, thereby rendering common health care-associated infections nearly impossible to treat. To determine the diversity of carbapenemase-encoding plasmids and assess their mobility among bacterial species, we performed comprehensive surveillance and genomic sequencing of carbapenem-resistant Enterobacteriaceae in the National Institutes of Health (NIH) Clinical Center patient population and hospital environment. We isolated a repertoire of carbapenemase-encoding Enterobacteriaceae, including multiple strains of Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Pantoea species. Long-read genome sequencing with full end-to-end assembly revealed that these organisms carry the carbapenem resistance genes on a wide array of plasmids. K. pneumoniae and E. cloacae isolated simultaneously from a single patient harbored two different carbapenemase-encoding plasmids, indicating that plasmid transfer between organisms was unlikely within this patient. We did, however, find evidence of horizontal transfer of carbapenemase-encoding plasmids between K. pneumoniae, E. cloacae, and C. freundii in the hospital environment. Our data, including full plasmid identification, challenge assumptions about horizontal gene transfer events within patients and identify possible connections between patients and the hospital environment. In addition, we identified a new carbapenemase-encoding plasmid of potentially high clinical impact carried by K. pneumoniae, E. coli, E. cloacae, and Pantoea species, in unrelated patients and in the hospital environment. PMID:25232178

  2. Prevalence of multidrug resistant uropathogenic bacteria in pediatric patients of a tertiary care hospital in eastern India.

    PubMed

    Mishra, Monali P; Sarangi, Rachita; Padhy, Rabindra N

    2016-01-01

    Today, because systemic infections such as urinary tract infection (UTI) affect even pediatric patients, antibiotic resistant bacteria have become a constant clinical challenge. In the present study, a total of 1054 urine samples were collected from pediatric patients over 18 months. From these samples, 510 isolates of pathogenic bacteria were collected using HiCrome UTI agar. Antibiotic sensitivity tests of isolates were performed using the Kirby-Bauer method. Two Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) and 7 Gram-negative bacteria (Citrobacter freundii, Enterobacter aerogenes, Escherichia coli, Klebsiella oxytoca, K. pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa) were isolated. Antibiograms of isolated bacteria were ascertained using antibiotics of 4 classes: aminoglycosides, β-lactams, fluoroquinolones and 2 stand-alones (co-trimoxazole and nitrofurantoin). Based on percent values of antibiotic resistance, isolated bacteria were (in decreasing order of number of isolated isolates): E. coli (109)>S. aureus (65)>E. faecalis (82)>E. aerogenes (64)>C. freundii (41)>P. aeruginosa (32)>K. pneumoniae (45)>K. oxytoca (50)>P. vulgaris (22). Surveillance results show that MDR isolates of 9 pathogenic bacteria were prevalent in the environment around the hospital. Thus, revisions to the antimicrobial stewardship program in this area of the country are required to increase clinician confidence in empiric therapy, which is often used for UTI cases. PMID:26617250

  3. Effects of pathogen-specific clinical mastitis on probability of conception in Holstein dairy cows.

    PubMed

    Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

    2014-11-01

    The objective of this study was to estimate the effects of pathogen-specific clinical mastitis (CM), occurring in different weekly intervals before or after artificial insemination (AI), on the probability of conception in Holstein cows. Clinical mastitis occurring in weekly intervals from 6 wk before until 6 wk after AI was modeled. The first 4 AI in a cow's lactation were included. The following categories of pathogens were studied: Streptococcus spp. (comprising Streptococcus dysgalactiae, Streptococcus uberis, and other Streptococcus spp.); Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level that can be detected from our microbiological procedures) observed in the culture sample and cases with contamination (≥ 3 pathogens in the sample); and other pathogens [including Citrobacter, yeasts, Trueperella pyogenes, gram-negative bacilli (i.e., gram-negative organisms other than E. coli, Klebsiella spp., Enterobacter, and Citrobacter), Corynebacterium bovis, Corynebacterium spp., Pasteurella, Enterococcus, Pseudomonas, Mycoplasma, Prototheca, and others]. Other factors included in the model were parity (1, 2, 3, 4 and higher), season of AI (winter, spring, summer, autumn), day in lactation of first AI, farm, and other non-CM diseases (retained placenta, metritis, ketosis, displaced abomasum). Data from 90,271 AI in 39,361 lactations in 20,328 cows collected from 2003/2004 to 2011 from 5 New York State dairy farms were analyzed in a generalized linear mixed model with a Poisson distribution. The largest reductions in probability of conception were associated with CM occurring in the week before AI or in the 2 wk following AI. Escherichia coli and Klebsiella spp. had the greatest adverse effects on probability of conception. The probability of conception for a cow with any combination of characteristics may be calculated based on the parameter estimates. These

  4. [Utility of pyrrolidonyl-arylamidase detection for typing Enterobacteriaceae and non-fermenting Gram-negative bacteria].

    PubMed

    Nicola, F; Centorbi, H; Bantar, C; Smayevsky, J; Bianchini, H

    1995-01-01

    Detection of pyrrolidonyl-aryl-amidase activity (PYR) is an important tool to identify gram-positive cocci, such as staphylococci, enterococci, streptococci, and other related genera. However, only few studies evaluating its usefulness with gram-negative rods have been published. Thus, a prospective study including 542 and 215 unique clinical isolates of Enterobacteriaceae and non-fermentative gram-negative rods, respectively, was undertaken. Strains were identified by conventional methods. PYR test was performed using a commercial kit, according to the manufacturer recommendations. Positive results were uniformly obtained for the PYR test with the following species: Citrobacter spp, Klebsiella spp, Enterobacter aerogenes, Enterobacter agglomerans group, Serratia marcescens and S. odorifera. On the other hand, negative results were uniformly displayed by E. coli (including inactive E. coli), Protease group, Salmonellia spp, Shigella spp, Acinetobacter spp, Burkholderia (Pseudomonas) cepacia and Flavobacterium spp. Variable results were shown in Pseudomonas aeruginosa, Stenotrophomonas (xanthomonas) malthophilia, Kluyvera cryocrescens, and Enterobacter cloacae. PYR test proved to be a reliable and simple tool to rapidly distinguish certain species belonging to Enterobacteriaceae (ie. Citrobacter freundii from Salmonella spp, and inactive E. coli from K. ozaenae). Further studies, including a wide diversity of species, are required to assess usefulness of the PYR test for the identification of non-fermentative gram-negative rods.

  5. Interleukin-1 (IL-1) signaling in intestinal stromal cells controls KC/ CXCL1 secretion, which correlates with recruitment of IL-22- secreting neutrophils at early stages of Citrobacter rodentium infection.

    PubMed

    Lee, Yong-Soo; Yang, Hyungjun; Yang, Jin-Young; Kim, Yeji; Lee, Su-Hyun; Kim, Ji Heui; Jang, Yong Ju; Vallance, Bruce A; Kweon, Mi-Na

    2015-08-01

    Attaching and effacing pathogens, including enterohemorrhagic Escherichia coli in humans and Citrobacter rodentium in mice, raise serious public health concerns. Here we demonstrate that interleukin-1 receptor (IL-1R) signaling is indispensable for protection against C. rodentium infection in mice. Four days after infection with C. rodentium, there were significantly fewer neutrophils (CD11b+ Ly6C+ Ly6G+) in the colons of IL-1R−/− mice than in wild-type mice. Levels of mRNA and protein of KC/CXCL1 were also significantly reduced in colon homogenates of infected IL-1R−/− mice relative to wild-type mice. Of note, infiltrated CD11b+ Ly6C+ Ly6G+ neutrophils were the main source of IL-22 secretion after C. rodentium infection. Interestingly, intestinal stromal cells isolated from IL-1R−/− mice secreted lower levels of KC/CXCL1 than stromal cells from wild-type mice during C. rodentium infection. Similar effects were found when mouse intestinal stromal cells and human nasal polyp stromal cells were treated with IL-1R antagonists (i.e., anakinra) in vitro. These results suggest that IL-1 signaling plays a pivotal role in activating mucosal stromal cells to secrete KC/CXCL1, which is essential for infiltration of IL-22-secreting neutrophils upon bacterial infection.

  6. Rapid identification of carbapenemase genes in gram-negative bacteria with an oligonucleotide microarray-based assay.

    PubMed

    Braun, Sascha D; Monecke, Stefan; Thürmer, Alexander; Ruppelt, Antje; Makarewicz, Oliwia; Pletz, Mathias; Reiβig, Annett; Slickers, Peter; Ehricht, Ralf

    2014-01-01

    Rapid molecular identification of carbapenemase genes in Gram-negative bacteria is crucial for infection control and prevention, surveillance and for epidemiological purposes. Furthermore, it may have a significant impact upon determining the appropriate initial treatment and greatly benefit for critically ill patients. A novel oligonucleotide microarray-based assay was developed to simultaneously detect genes encoding clinically important carbapenemases as well as selected extended (ESBL) and narrow spectrum (NSBL) beta-lactamases directly from clonal culture material within few hours. Additionally, a panel of species specific markers was included to identify Escherichia coli, Pseudomonas aeruginosa, Citrobacter freundii/braakii, Klebsiella pneumoniae and Acinetobacter baumannii. The assay was tested using a panel of 117 isolates collected from urinary, blood and stool samples. For these isolates, phenotypic identifications and susceptibility tests were available. An independent detection of carbapenemase, ESBL and NSBL genes was carried out by various external reference laboratories using PCR methods. In direct comparison, the microarray correctly identified 98.2% of the covered carbapenemase genes. This included blaVIM (13 out of 13), blaGIM (2/2), blaKPC (27/27), blaNDM (5/5), blaIMP-2/4/7/8/13/14/15/16/31 (10/10), blaOXA-23 (12/13), blaOXA-40-group (7/7), blaOXA-48-group (32/33), blaOXA-51 (1/1) and blaOXA-58 (1/1). Furthermore, the test correctly identified additional beta-lactamases [blaOXA-1 (16/16), blaOXA-2 (4/4), blaOXA-9 (33/33), OXA-10 (3/3), blaOXA-51 (25/25), blaOXA-58 (2/2), CTX-M1/M15 (17/17) and blaVIM (1/1)]. In direct comparison to phenotypical identification obtained by VITEK or MALDI-TOF systems, 114 of 117 (97.4%) isolates, including Acinetobacter baumannii (28/28), Enterobacter spec. (5/5), Escherichia coli (4/4), Klebsiella pneumoniae (62/63), Klebsiella oxytoca (0/2), Pseudomonas aeruginosa (12/12), Citrobacter freundii (1/1) and

  7. Effect of coiled-coil peptides on the function of the type III secretion system-dependent activity of enterohemorragic Escherichia coli O157:H7 and Citrobacter rodentium.

    PubMed

    Larzábal, Mariano; Zotta, Elsa; Ibarra, Cristina; Rabinovitz, Bettina C; Vilte, Daniel A; Mercado, Elsa C; Cataldi, Ángel

    2013-01-01

    Many animal and human pathogenic Gram-negative bacteria such as Salmonella, Yersinia, enterohemorrhagic Escherichia coli (EHEC), and enteropathogenic Escherichia coli (EPEC) possess a type III secretion system (TTSS) that is used to deliver virulence proteins directly into the host cell. Recent evidence has suggested that CoilA and CoilB, two synthetic peptides corresponding to coiled-coil domains of the translocator protein EspA, are effective in inhibiting the action of TTSS from EPEC. In the current study, the action of these coiled-coil peptides on the TTSS of EHEC O157:H7 and Citrobacter rodentium was examined. CoilA and CoilB showed to be effective in reducing the red blood cell lysis mediated by EHEC O157:H7 and the in vitro secretion of translocator proteins EspB and EspD by EHEC O157:H7 and EspD by C. rodentium. Treatment of mice with CoilA and CoilB peptides prevented colon damage when the animals were inoculated with C. rodentium. Colon samples of the non-treated group showed areas with loss of superficial epithelium, damaged cells, and endoluminal mononuclear inflammatory infiltrate, consistent with histological lesions induced by C. rodentium, whereas mice treated with the synthetic peptides displayed normal surface epithelium showing a similar structure as the uninfected control group. These encouraging results prompt us to test coiled-coil peptides as treatment or vaccines in other models of bacterial infections in future work. PMID:23312797

  8. Clinical Research and Clinical Trials

    MedlinePlus

    ... you can get involved. Doing your own clinical research project? Then select the Guidance for Clinical Researchers link to learn more about the NICHD's clinical research processes and policies. Last Reviewed: 03/06/2012 ...

  9. [Technical support in the testing of microoganisms for their ability to accumulate strontium and cesium from aqueous solutions]. Final reports, Task order No. 2

    SciTech Connect

    Not Available

    1987-06-15

    This report describes the binding of cesium and strontium ions from aqueous solution in a variety of microorganisms. Data is provided on the absorption by Ashbya gossyppi, Chlorella pyrenoidosa, Candida sp. Ml13, Saccharomyces cerevisiae, Scenedesmus obliqus, Streptococcus mutans, Anabaena flosaquae, Escherichia coli, Streptomyces viridochromogenes, Chlamydomonas reinhardtii, Rhizopus oryzae, Bacillus megaterium, Micrococcus luteus, Zoogloea ramigera, Coelastrum proboscideum, Pseudomonas aeruginosa, Citrobacter freundii, Paecilomyces marquandi, and Caulobacter fusiformis.

  10. Extended-spectrum β-lactamase-producing Enterobacteriaceae isolated from feces of Falconidae, Accipitridae, and Laridae in bird rescue centers in Belgium.

    PubMed

    Rouffaer, Lieze Oscar; Haesebrouck, Freddy; Martel, An

    2014-10-01

    The presence of extended-spectrum β-lactamase- and Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae was investigated in feces and in choanal and cloacal swabs of birds in rescue centers. Ceftiofur-resistant Escherichia coli and Citrobacter freundii were isolated from feces of birds of prey (12% positive) and a group of gulls. The genes blaCTX-M-1, blaCTX-M-15, and blaCTX-M-32 coded for resistance. PMID:25075542

  11. Isolation of some pathogenic bacteria from the great spruce bark beetle, Dendroctonus micans and its specific predator, Rhizophagus grandis.

    PubMed

    Yaman, M; Ertürk, O; Aslan, I

    2010-01-01

    Some bacteria were isolated from Dendroctonus micans and its specific predator, Rhizophagus grandis. Six bacteria from D. micans were identified as Bacillus pumilus, Enterobacter intermedius, Citrobacter freundii, Cellulomonas flavigena, Microbacterium liquefaciens and Enterobacter amnigenus, three bacteria from R. grandis as Klebsiella pneumoniae, Pantoea agglomerans and Serratia grimesii, on the basis of fatty acid methyl ester analysis and carbon utilization profile by using Microbial Identification and Biolog Microplate Systems. Their insecticidal effects were tested on larvae and adults of D. micans.

  12. Association of tellurium resistance and bacteriophage inhibition conferred by R plasmids.

    PubMed Central

    Taylor, D E; Summers, A O

    1979-01-01

    Concomitant resistance to tellurium compounds (Ter) and inhibition of coli-phage development (Phi) are properties mediated by many H2 incompatibility group R plasmids which have been isolated from diverse bacterial and geographic sources. Ter plasmids from tellurium-resistant bacteria that were isolated from sewage and industrial wastes also mediated phage inhibition. Of these Ter plasmids, three from Citrobacter freundii belonged to the H incompatibility group, whereas three from Klebsiella pneumoniae did not. Images PMID:374351

  13. Evaluation of a new selective chromogenic agar medium for detection of extended-spectrum beta-lactamase-producing Enterobacteriaceae.

    PubMed

    Glupczynski, Youri; Berhin, Catherine; Bauraing, Caroline; Bogaerts, Pierre

    2007-02-01

    A novel chromogenic agar medium (ESBL-Bx; bioMérieux, Marcy l'Etoile, France) was compared to MacConkey agar supplemented with 2 mg ceftazidime/liter (MCKC) for the selective isolation and presumptive identification of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae directly from clinical samples. Of a total of 644 clinical specimens (including 551 fecal samples), 496 yielded no growth and 148 yielded growth on one or both media. Overall, 44 ESBL-producing Enterobacteriaceae strains (Escherichia coli [n=17], Enterobacter aerogenes [n=17], Klebsiella spp. [n=5], and Citrobacter freundii [n=5]) were isolated from 37 specimens by a combination of both methods after 18 to 24 h of incubation. The sensitivities were 97.7 and 84.1% for ESBL-Bx and MCKC, respectively, with 43 ESBL-positive strains isolated as colored colonies from 36 specimens on ESBL-Bx versus 37 ESBL-positive organisms isolated from 32 specimens on MCKC. The specificities by specimens were 89 and 91% for ESBL-Bx and MCKC, respectively. On either one of the two media, natural AmpC-hyperproducing Enterobacter spp. (n=25) and Citrobacter spp. (n=14) were the most common false positives as well as non-ESBL-producing Klebsiella oxytoca (n=18) on ESBL-Bx and Morganella morganii (n=10) on MCKC. We conclude that ESBL-Bx is a sensitive and specific medium for the isolation of ESBL-producing Enterobacteriaceae from clinical samples. The main advantages of ESBL-Bx over MCKC reside in its chromogenic character and its sensitivity and selectivity, which enabled the recovery and presumptive identification of most ESBL-producing Enterobacteriaceae within 24 h and reduced by 27% the need for unnecessary identification and confirmation of ESBL testing when disregarding all colorless colonies growing on this medium.

  14. Cost-Effective and Rapid Presumptive Identification of Gram-Negative Bacilli in Routine Urine, Pus, and Stool Cultures: Evaluation of the Use of CHROMagar Orientation Medium in Conjunction with Simple Biochemical Tests

    PubMed Central

    Ohkusu, Kiyofumi

    2000-01-01

    The algorithm for a new identification system was designed on the basis of colony color and morphology on CHROMagar Orientation medium in conjunction with simple biochemical tests such as indole (IND), lysine decarboxylase (LDC), and ornithine decarboxylase (ODC) utilization tests with gram-negative bacilli isolated from urine samples as well as pus, stool, and other clinical specimens by the following colony characteristics, biochemical reactions, and serological results: pinkish to red, IND positive (IND+), Escherichia coli; metallic blue, IND+, LDC+, and ODC negative (ODC−), Klebsiella oxytoca; IND+, LDC−, and ODC+, Citrobacter diversus; IND+ or IND−, LDC−, and ODC−, Citrobacter freundii; IND−, LDC+, and ODC+, Enterobacter aerogenes; IND−, LDC−, and ODC+, Enterobacter cloacae; IND−, LDC+, and ODC−, Klebsiella pneumoniae; diffuse brown and IND+, Morganella morganii; IND−, Proteus mirabilis; aqua blue, Serratia marcescens; bluish green and IND+, Proteus vulgaris; transparent yellow-green, serology positive, Pseudomonas aeruginosa; clear and serology positive, Salmonella sp.; other colors and reactions, the organism was identified by the full identification methods. The accuracy and cost-effectiveness of this new system were prospectively evaluated. During an 8-month period, a total of 345 specimens yielded one or more gram-negative bacilli. A total of 472 gram-negative bacillus isolates were detected on CHROMagar Orientation medium. For 466 of the isolates (98.7%), no discrepancies in the results were obtained on the basis of the identification algorithm. The cost of identification of gram-negative bacilli during this period was reduced by about 70%. The results of this trial for the differentiation of the most commonly encountered gram-negative pathogens in clinical specimens with the new algorithm were favourable in that it permitted reliable detection and presumptive identification. In addition, this rapid identification system not only

  15. Cost-effective and rapid presumptive identification of gram-negative bacilli in routine urine, pus, and stool cultures: evaluation of the use of CHROMagar orientation medium in conjunction with simple biochemical tests.

    PubMed

    Ohkusu, K

    2000-12-01

    The algorithm for a new identification system was designed on the basis of colony color and morphology on CHROMagar Orientation medium in conjunction with simple biochemical tests such as indole (IND), lysine decarboxylase (LDC), and ornithine decarboxylase (ODC) utilization tests with gram-negative bacilli isolated from urine samples as well as pus, stool, and other clinical specimens by the following colony characteristics, biochemical reactions, and serological results: pinkish to red, IND positive (IND(+)), Escherichia coli; metallic blue, IND(+), LDC(+), and ODC negative (ODC(-)), Klebsiella oxytoca; IND(+), LDC(-), and ODC(+), Citrobacter diversus; IND(+) or IND(-), LDC(-), and ODC(-), Citrobacter freundii; IND(-), LDC(+), and ODC(+), Enterobacter aerogenes; IND(-), LDC(-), and ODC(+), Enterobacter cloacae; IND(-), LDC(+), and ODC(-), Klebsiella pneumoniae; diffuse brown and IND(+), Morganella morganii; IND(-), Proteus mirabilis; aqua blue, Serratia marcescens; bluish green and IND(+), Proteus vulgaris; transparent yellow-green, serology positive, Pseudomonas aeruginosa; clear and serology positive, Salmonella sp.; other colors and reactions, the organism was identified by the full identification methods. The accuracy and cost-effectiveness of this new system were prospectively evaluated. During an 8-month period, a total of 345 specimens yielded one or more gram-negative bacilli. A total of 472 gram-negative bacillus isolates were detected on CHROMagar Orientation medium. For 466 of the isolates (98.7%), no discrepancies in the results were obtained on the basis of the identification algorithm. The cost of identification of gram-negative bacilli during this period was reduced by about 70%. The results of this trial for the differentiation of the most commonly encountered gram-negative pathogens in clinical specimens with the new algorithm were favourable in that it permitted reliable detection and presumptive identification. In addition, this rapid

  16. Clinical Trials

    MedlinePlus

    Clinical trials are research studies that test how well new medical approaches work in people. Each study answers ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...

  17. Enzymatic degradation of polygalacturonic acid by Yersinia and Klebsiella species in relation to clinical laboratory procedures.

    PubMed

    Starr, M P; Chatterjee, A K; Starr, P B; Buchanan, G E

    1977-10-01

    As scored by several specified plating procedures, clinical and environmental strains of Yersinia enterocolitica, Yersinia pseudotuberculosis, and Klebsiella pneumoniae "Oxytocum" showed detectable, albeit generally weak, ability to digest polygalacturonic (pectic) acid. None of these bacterial strains had the vigorous and rapid pectolytic activity on these polygalacturonic acid-containing media that is typical of soft-rot Erwinia species, although some of the Oxytocum strains came fairly close. Analyses of the pectolytic enzyme contents of the cells and culture supernatants of the Yersinia and Klebsiella species revealed that readily detectable quantities of cell-bound polygalacturonic acid trans-eliminase and hydrolytic polygalacturonase were formed by the Yersinia and Klebsiella species; however, the total units of enzyme activity produced by these bacteria were, in general, lower than were produced by soft-rot Erwinia species. Furthermore, unlike the situation in soft-rot Erwinia cultures, these pectolytic enzymes of Yersinia and Klebsiella species were not excreted rapidly and massively into the growth medium. Cultures of other enterobacteria (Citrobacter species, Enterobacter species, Erwinia amylovora, Erwinia herbicola, Escherichia coli, Proteus species, Salmonella typhimurium, and Serratia marcescens) showed no pectolytic ability whatsoever by any of the plating procedures used and (to the extent they were so examined) produced no pectolytic enzymes detectable either in their cells or culture supernatants. This slow or weak release of pectolytic enzymes by Yersinia and Klebsiella species has a bearing on clinical laboratory procedures suitable for detecting their pectolytic activity; methods adequate for this purpose are detailed.

  18. Enzymatic Degradation of Polygalacturonic Acid by Yersinia and Klebsiella Species in Relation to Clinical Laboratory Procedures

    PubMed Central

    Starr, Mortimer P.; Chatterjee, Arun K.; Starr, Phoebe B.; Buchanan, Gordon E.

    1977-01-01

    As scored by several specified plating procedures, clinical and environmental strains of Yersinia enterocolitica, Yersinia pseudotuberculosis, and Klebsiella pneumoniae “Oxytocum” showed detectable, albeit generally weak, ability to digest polygalacturonic (pectic) acid. None of these bacterial strains had the vigorous and rapid pectolytic activity on these polygalacturonic acid-containing media that is typical of soft-rot Erwinia species, although some of the Oxytocum strains came fairly close. Analyses of the pectolytic enzyme contents of the cells and culture supernatants of the Yersinia and Klebsiella species revealed that readily detectable quantities of cell-bound polygalacturonic acid trans-eliminase and hydrolytic polygalacturonase were formed by the Yersinia and Klebsiella species; however, the total units of enzyme activity produced by these bacteria were, in general, lower than were produced by soft-rot Erwinia species. Furthermore, unlike the situation in soft-rot Erwinia cultures, these pectolytic enzymes of Yersinia and Klebsiella species were not excreted rapidly and massively into the growth medium. Cultures of other enterobacteria (Citrobacter species, Enterobacter species, Erwinia amylovora, Erwinia herbicola, Escherichia coli, Proteus species, Salmonella typhimurium, and Serratia marcescens) showed no pectolytic ability whatsoever by any of the plating procedures used and (to the extent they were so examined) produced no pectolytic enzymes detectable either in their cells or culture supernatants. This slow or weak release of pectolytic enzymes by Yersinia and Klebsiella species has a bearing on clinical laboratory procedures suitable for detecting their pectolytic activity; methods adequate for this purpose are detailed. PMID:334794

  19. Clinical challenge.

    PubMed

    2016-09-01

    Questions for this month's clinical challenge are based on articles in this issue. The clinical challenge is endorsed by the RACGP Quality Improvement and Continuing Professional Development (QI&CPD) program and has been allocated four Category 2 points (Activity ID:59922). Answers to this clinical challenge are available immediately following successful completion online at http://gplearning.racgp.org.au. Clinical challenge quizzes may be completed at any time throughout the 2014-16 triennium; therefore, the previous months' answers are not published. Each of the questions or incomplete statements below is followed by four suggested answers or completions. Select the most appropriate statement as your answer. PMID:27606376

  20. Molecular epidemiology of TEM-3 (CTX-1) beta-lactamase.

    PubMed Central

    Petit, A; Gerbaud, G; Sirot, D; Courvalin, P; Sirot, J

    1990-01-01

    A total of 33 clinical isolates encoding TEM-3 (CTX-1) from four French hospitals were studied. The strains belonged to seven species, Klebsiella pneumoniae (n = 24), Escherichia coli (n = 3), Serratia marcescens (n = 2), Citrobacter freundii (n = 1), Enterobacter aerogenes (n = 1), Enterobacter cloacae (n = 1), and Klebsiella oxytoca (n = 1). All the strains harbored an Inc7 or M self-transferable plasmid with a size of approximately 85 kilobases. The plasmids had closely related EcoRI, HincII, HindIII, and PvuII restriction endonuclease-generated patterns and conferred resistance to all beta-lactams, except cephamycins and imipenem; to tetracycline, because of the presence of the genes blatem-3 and tetC, respectively, as determined by hybridization with specific probes; and to sulfonamide. Depending on the presence or absence and level of expression of the genes aacA4, aadA, and dfrI and of insertion element IS15, four types of plasmids could be distinguished. Plasmid pCFF04, the prototype plasmid encoding TEM-3, was widespread and appeared, by Southern hybridization, as the progenitor of the other types of replicons. The plasmid epidemic responsible for dissemination of TEM-3 in clinical isolates of members of the family Enterobacteriaceae may have originated in S. marcescens since pCFF04 was first detected in this species. Images PMID:2327769

  1. In Vitro Antibacterial Efficacy of 21 Indian Timber-Yielding Plants Against Multidrug-Resistant Bacteria Causing Urinary Tract Infection

    PubMed Central

    Mishra, Monali P.; Padhy, Rabindra N.

    2013-01-01

    Objectives To screen methanolic leaf extracts of 21 timber-yielding plants for antibacterial activity against nine species of uropathogenic bacteria isolated from clinical samples of a hospital (Enterococcus faecalis, Staphylococcus aureus, Acinetobacter baumannii, Citrobacter freundii, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa). Methods Bacterial strains were subjected to antibiotic sensitivity tests by the Kirby–Bauer's disc diffusion method. The antibacterial potentiality of leaf extracts was monitored by the agar-well diffusion method with multidrug-resistant (MDR) strains of nine uropathogens. Results Two Gram-positive isolates, E. faecalis and S. aureus, were resistant to 14 of the 18 antibiotics used. Gram-negative isolates A. baumannii, C. freundii, E. aerogenes, E. coli, K. pneumoniae, P. mirabilis, and P. aeruginosa were resistant to 10, 12, 9, 11, 11, 10, and 11 antibiotics, respectively, of the 14 antibiotics used. Methanolic leaf extracts of Anogeissus acuminata had the maximum zone of inhibition size—29 mm against S. aureus and 28 mm against E. faecalis and P. aeruginosa. Cassia tora had 29 mm as the zone of inhibition size for E. faecalis, E. aerogenes, and P. aeruginosa. Based on the minimum inhibitory concentration and minimum bactericidal concentration values, the most effective 10 plants against uropathogens could be arranged in decreasing order as follows: C. tora > A. acuminata > Schleichera oleosa > Pterocarpus santalinus > Eugenia jambolana > Bridelia retusa > Mimusops elengi > Stereospermum kunthianum > Tectona grandis > Anthocephalus cadamba. The following eight plants had moderate control capacity: Artocarpus heterophyllus, Azadirachta indica, Dalbergia latifolia, Eucalyptus citriodora, Gmelina arborea, Pongamia pinnata, Pterocarpus marsupium, and Shorea robusta. E. coli, followed by A. baumannii, C. freundii, E. aerogenes, P. mirabilis, and P

  2. Clinical photography.

    PubMed

    Jakowenko, Janelle

    2009-01-01

    Digital cameras, when used correctly, can provide the basis for telemedicine services. The increasing sophistication of digital cameras, combined with the improved speed and availability of the Internet, make them an instrument that every health-care professional should be familiar with. Taking satisfactory images of patients requires clinical photography skills. Photographing charts, monitors, X-ray films and specimens also requires expertise. Image capture using digital cameras is often done with insufficient attention, which can lead to inaccurate study results. The procedures in clinical photography should not vary from camera to camera, or from country to country. Taking a photograph should be a standardised process. There are seven main scenarios in clinical photography and health professionals who use cameras should be familiar with all of them. Obtaining informed consent prior to photography should be a normal part of the clinical photography routine.

  3. Clinical Trials

    MedlinePlus

    ... of visits, and any adjustments to treatment. (back) Requirements for Participation Admission into a clinical trial is based on a rigid set of requirements. You must be diagnosed with the illness that ...

  4. Clinical neuroimaging

    SciTech Connect

    Theodore, W.H.

    1988-01-01

    This book contains chapters on neuroimaging. Included are the following chapters: diagnostic neuroimaging in stroke, position emission tomography in cerebrovascular disease: clinical applications, and neuroradiologic work-up of brain tumors.

  5. Clinical supervision.

    PubMed

    Goorapah, D

    1997-05-01

    The introduction of clinical supervision to a wider sphere of nursing is being considered from a professional and organizational point of view. Positive views are being expressed about adopting this concept, although there are indications to suggest that there are also strong reservations. This paper examines the potential for its success amidst the scepticism that exists. One important question raised is whether clinical supervision will replace or run alongside other support systems.

  6. Increased prevalence of carbapenem resistant Enterobacteriaceae in hospital setting due to cross-species transmission of the bla NDM-1 element and clonal spread of progenitor resistant strains.

    PubMed

    Wang, Xuan; Chen, Gongxiang; Wu, Xiaoyan; Wang, Liangping; Cai, Jiachang; Chan, Edward W; Chen, Sheng; Zhang, Rong

    2015-01-01

    This study investigated the transmission characteristics of carbapenem-resistant Enterobacteriaceae (CRE) strains collected from a hospital setting in China, in which consistent emergence of CRE strains were observable during the period of May 2013 to February 2014. Among the 45 CRE isolates tested, 21 (47%) strains were found to harbor the bla NDM-1 element, and the rest of 24 CRE strains were all positive for bla KPC-2. The 21 bla NDM-1-borne strains were found to comprise multiple Enterobacteriaceae species including nine Enterobacter cloacae, three Escherichia coli, three Citrobacter freundii, two Klebsiella pneumoniae, two Klebsiella oxytoca, and two Morganella morganii strains, indicating that cross-species transmission of bla NDM-1 is a common event. Genetic analyses by PFGE and MLST showed that, with the exception of E. coli and E. cloacae, strains belonging to the same species were often genetically unrelated. In addition to bla NDM-1, several CRE strains were also found to harbor the bla KPC-2, bla VIM-1, and bla IMP-4 elements. Conjugations experiments confirmed that the majority of carbapenem resistance determinants were transferable. Taken together, our findings suggest that transmission of mobile resistance elements among members of Enterobacteriaceae and clonal spread of CRE strains may contribute synergistically to a rapid increase in the population of CRE in clinical settings, prompting a need to implement more rigorous infection control measures to arrest such vicious transmission cycle in CRE-prevalent areas. PMID:26136735

  7. Active Shiga-Like Toxin Produced by Some Aeromonas spp., Isolated in Mexico City

    PubMed Central

    Palma-Martínez, Ingrid; Guerrero-Mandujano, Andrea; Ruiz-Ruiz, Manuel J.; Hernández-Cortez, Cecilia; Molina-López, José; Bocanegra-García, Virgilio; Castro-Escarpulli, Graciela

    2016-01-01

    Shiga-like toxins (Stx) represent a group of bacterial toxins involved in human and animal diseases. Stx is produced by enterohemorrhagic Escherichia coli, Shigella dysenteriae type 1, Citrobacter freundii, and Aeromonas spp.; Stx is an important cause of bloody diarrhea and hemolytic uremic syndrome (HUS). The aim of this study was to identify the stx1/stx2 genes in clinical strains and outer membrane vesicles (OMVs) of Aeromonas spp., 66 strains were isolated from children who live in Mexico City, and Stx effects were evaluated in Vero cell cultures. The capacity to express active Stx1 and Stx2 toxins was determined in Vero cell cultures and the concentration of Stx was evaluated by 50% lethal dose (LD50) assays, observing inhibition of damaged cells by specific monoclonal antibodies. The results obtained in this study support the hypothesis that the stx gene is another putative virulence factor of Aeromonas, and since this gene can be transferred horizontally through OMVs this genus should be included as a possible causal agents of gastroenteritis and it should be reported as part of standard health surveillance procedures. Furthermore, these results indicate that the Aeromonas genus might be a potential causative agent of HUS. PMID:27725813

  8. Increased prevalence of carbapenem resistant Enterobacteriaceae in hospital setting due to cross-species transmission of the blaNDM-1 element and clonal spread of progenitor resistant strains

    PubMed Central

    Wang, Xuan; Chen, Gongxiang; Wu, Xiaoyan; Wang, Liangping; Cai, Jiachang; Chan, Edward W.; Chen, Sheng; Zhang, Rong

    2015-01-01

    This study investigated the transmission characteristics of carbapenem-resistant Enterobacteriaceae (CRE) strains collected from a hospital setting in China, in which consistent emergence of CRE strains were observable during the period of May 2013 to February 2014. Among the 45 CRE isolates tested, 21 (47%) strains were found to harbor the blaNDM-1 element, and the rest of 24 CRE strains were all positive for blaKPC-2. The 21 blaNDM-1—borne strains were found to comprise multiple Enterobacteriaceae species including nine Enterobacter cloacae, three Escherichia coli, three Citrobacter freundii, two Klebsiella pneumoniae, two Klebsiella oxytoca, and two Morganella morganii strains, indicating that cross-species transmission of blaNDM-1 is a common event. Genetic analyses by PFGE and MLST showed that, with the exception of E. coli and E. cloacae, strains belonging to the same species were often genetically unrelated. In addition to blaNDM-1, several CRE strains were also found to harbor the blaKPC-2, blaVIM-1, and blaIMP-4 elements. Conjugations experiments confirmed that the majority of carbapenem resistance determinants were transferable. Taken together, our findings suggest that transmission of mobile resistance elements among members of Enterobacteriaceae and clonal spread of CRE strains may contribute synergistically to a rapid increase in the population of CRE in clinical settings, prompting a need to implement more rigorous infection control measures to arrest such vicious transmission cycle in CRE-prevalent areas. PMID:26136735

  9. Comparative characterization of the cephamycinase blaCMY-1 gene and its relationship with other beta-lactamase genes.

    PubMed Central

    Bauernfeind, A; Stemplinger, I; Jungwirth, R; Wilhelm, R; Chong, Y

    1996-01-01

    A plasmidic beta-lactamase which hydrolyzed cephamycins was first detected and reported in 1989. At that time its description was restricted to phenotypic characteristics. We analyzed nucleotide sequence of its gene and explored it genetic relationship with other bla genes. The deduced amino acid sequence of the blaCMY-1 product was compared with those of other known plasmidic cephamycinases and of chromosomal AmpC beta-lactamases. The results indicate that the relationship of CMY-1 is closest to MOX-1 among the plasmidic cephamycinases and to AmpC of Pseudomonas aeruginosa among the chromosomal cephalosporinases. We conclude that the plasmidic cephamycinases described up to now may be classified into three families, as follows: CMY-1, MOX-1, and FOX-1 with AmpC of P. aeruginosa; CMY-2, BIL-1 and LAT-1 with AmpC of Citrobacter freundii; and MIR-1 with AmpC of Enterobacter cloacae. Plasmidic cephamycinases are now recognized as clinically relevant class C beta-lactamases. PMID:8843306

  10. Mass mortality in ornamental fish, Cyprinus carpio koi caused by a bacterial pathogen, Proteus hauseri.

    PubMed

    Kumar, Raj; Swaminathan, T Raja; Kumar, Rahul G; Dharmaratnam, Arathi; Basheer, V S; Jena, J K

    2015-09-01

    Moribund koi carp, Cyprinus carpio koi, from a farm with 50% cumulative mortality were sampled with the aim of isolating and detecting the causative agent. Three bacterial species viz., Citrobacter freundii (NSCF-1), Klebsiella pneumoniae (NSKP-1) and Proteus hauseri [genomospecies 3 of Proteus vulgaris Bio group 3] (NSPH-1) were isolated, identified and characterized on the basis of biochemical tests and sequencing of the 16S rDNA gene using universal bacterial primers. Challenge experiments with these isolates using healthy koi carp showed that P. hauseri induced identical clinical and pathological states within 3 d of intramuscular injection. The results suggest P. hauseri (NSPH-1) was the causative agent. In phylogenetic analysis, strain NSPH-1 formed a distinct cluster with other P. hauseri reference strains with ≥99% sequence similarity. P. hauseri isolates were found sensitive to Ampicillin, Cefalexin, Ciprofloxacin and Cefixime and resistant to Gentamycin, Oxytetracycline, Chloramphenicol, and Kanamycin. The affected fish recovered from the infection after ciprofloxacin treatment. PMID:26028178

  11. Clinical trials

    PubMed Central

    Garnham, J. C.

    1974-01-01

    The choice of standard drugs to be used in clinical trials must be based on consideration of human absorption data, in vitro characteristics, possible interactions, comparative efficacy and safety, previous data regarding the standard in relation to the syndrome to be studied, and correlation of blood levels, effectiveness and safety. PMID:4465771

  12. Clinical cytomics

    NASA Astrophysics Data System (ADS)

    Tárnok, Attila; Mittag, Anja; Lenz, Dominik

    2006-02-01

    The goal of predictive medicine is the detection of changes in patient's state prior to the clinical manifestation of the deterioration of the patients current status. Therefore, both the diagnostic of diseases like cancer, coronary atherosclerosis or congenital heart failure and the prognosis of the effect specific therapeutics on patients outcome are the main fields of predictive medicine. Clinical Cytomcs is based on the analysis of specimens from the patient by Cytomic technologies that are mainly imaging based techniques and their combinations with other assays. Predictive medicine aims at the recognition of the "fate" of each individual patients in order to yield unequivocal indications for decision making (i.e. how does the patient respond to therapy, react to medication etc.). This individualized prediction is based on the Predictive Medicine by Clinical Cytomics concept. These considerations have recently stimulated the idea of the Human Cytome Project. A major focus of the Human Cytome Project is multiplexed cy-tomic analysis of individual cells of the patient, extraction of predictive information and individual prediction that merges into individualized therapy. Although still at the beginning, Clinical Cytomics is a promising new field that may change therapy in the near future for the benefit of the patients.

  13. [Clinical pathology].

    PubMed

    Dimitrijević, Jovan

    2006-05-01

    This work describes the basic elements of pathology used in clinical practice. Pathology plays an important role in clinical and scientific work, but only a few areas of pathology will be covered. Although the contribution of oncological and surgical pathology to therapy is the most well known, the cases chosen here will involve infectious pathology, diseases of the kidney and the liver, autoimmune diseases, as well as organ transplantation. Especially important is the description of methods that enable more accurate morphological diagnoses, such as histochemistry, immunohistochemistry, immunofluorescence, and electronic microscopy. Previous experience and joint work with clinical doctors have enabled the definition of significant morphological elements as well as of essential methods of pathohistological diagnosis. Besides, as is often the case, although disease symptoms are difficult to discern and biochemical results do not show significant changes compared to normal values, the results of biopsy come as a surprise to clinical doctors. For example, in virus hepatitis B involving so-called asymptomatic HBsAg carriers, we discovered every morphological form of hepatitis, from minimal lesions to chronic, persistent, and active hepatitis. With hepatitis C, certain morphological lesions point to the etiopathogenesis of this disease and thus help to confirm the diagnosis and to instigate therapy on time. Another significant experience involves kidney biopsies in cases when clinical findings are asymptomatic. Often, in such cases, morphological findings point to glomerulonephritis and glomerulopathy at different stages. Timely and subtle morphological diagnostics offer a more precise explanation for the pathological injury of tissues than other diagnostic methods. In this way, by adopting new methods, the work of pathologists is included more and more in everyday clinical practice. The inclusion of pathologists in a transplantation team makes sure a proper selection of

  14. Clinical biochemistry

    NASA Technical Reports Server (NTRS)

    Alexander, W. C.; Leach, C. S.; Fischer, C. L.

    1975-01-01

    The objectives of the biochemical studies conducted for the Apollo program were (1) to provide routine laboratory data for assessment of preflight crew physical status and for postflight comparisons; (2) to detect clinical or pathological abnormalities which might have required remedial action preflight; (3) to discover as early as possible any infectious disease process during the postflight quarantine periods following certain missions; and (4) to obtain fundamental medical knowledge relative to man's adjustment to and return from the space flight environment. The accumulated data presented suggest that these requirements were met by the program described. All changes ascribed to the space flight environment were subtle, whereas clinically significant changes were consistent with infrequent illnesses unrelated to the space flight exposure.

  15. Clinical bioethics.

    PubMed

    De Oliveira, Reinaldo Ayer; Oselka, Gabriel; Cohen, Cláudio; Costa, Sérgio ibiapina Ferreira

    2008-01-01

    Clinical bioethics was born out of the need to introduce different ethical values involved in the relationships among physician, patient and health institutions which are outside the technical-scientific framework of routine medical practice. Physicians tend to adopt the norms and rules provided for in the Medical Ethics Code to guide the exercising of their professional practice. However, it has recently become challenging to apply these norms to all conduct since some issues faced in the professional practice are simply not provided for by such norms. Ethical consideration in practice drawing solely on the medical ethics code in Brazil has proved insufficient, both in the context of universal issues such as organ transplants, start and end-of-life, as well as in addressing specific issues such as allocation of funds for health. Clinical bioethics employs clinical cases and situations as an instrument for discussion. These discussions entail analysis of not only the facts and circumstances surrounding each case, but also the values which lead to patients, health teams and institutions opting to recommend, accept or refuse a given conduct.

  16. Molecular Diagnosis of Urinary Tract Infections by Semi-Quantitative Detection of Uropathogens in a Routine Clinical Hospital Setting

    PubMed Central

    van der Zee, Anneke; Roorda, Lieuwe; Bosman, Gerda; Ossewaarde, Jacobus M.

    2016-01-01

    Background The objective of our study was the development of a semi-quantitative real-time PCR to detect uropathogens. Two multiplex PCR reactions were designed to detect Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus mirabilis, Enterococcus faecalis, and Pseudomonas aeruginosa. 16S based PCR was performed in parallel to detect Gram-positive and Gram-negative bacteria. Firstly to identify non-targeted agents of infection in the same urine specimen, and secondly to quantify background flora. The method was evaluated in comparison with standard bacterial culture, and a commercial PCR kit for detection of uropathogens. Findings Analysis with a known panel of 116 clinical isolates yielded a PCR specificity of 100%. Analysis of urine specimens from 211 patients revealed a high correlation of PCR Cq values with both culture positivity and quantity. Concordance between PCR and culture was 98% when both methods yielded results. PCR was found to be more sensitive than culture. With a cut-off Cq value of 33, the negative predictive value of PCR was 94%. The 16S PCR confirmed most results. One specimen was positive by 16S PCR suggesting another cause of infection not detected by the specific PCR assays. Conclusion We conclude that it is feasible to detect and identify uropathogens by multiplex real-time PCR assay. PMID:26954694

  17. Participating in Clinical Trials

    MedlinePlus

    ... this page please turn Javascript on. Participating in Clinical Trials About Clinical Trials A Research Study With Human Subjects A clinical ... to treat or cure a disease. Phases of Clinical Trials Clinical trials of drugs are usually described based ...

  18. Clinical arthrography

    SciTech Connect

    Arndt, R.; Horns, J.W.; Gold, R.H.; Blaschke, D.D.

    1985-01-01

    This book deals with the method and interpretation of arthrography of the shoulder, knee, ankle, elbow, hip, wrist, and metacarpophalangeal, interphalangeal, and temporomandibular joints. The emphasis is on orthopaedic disorders, usually of traumatic origin, which is in keeping with the application of arthrography in clinical practice. Other conditions, such as inflammatory and degenerative diseases, congenital disorders and, in the case of the hip, arthrography of reconstructive joint surgery, are included. Each chapter is devoted to one joint and provides a comprehensive discussion on the method of arthrography, including single and double contrast techniques where applicable, normal radiographic anatomy, and finally, the interpretation of the normal and the abnormal arthrogram.

  19. Clinical neuroimaging

    SciTech Connect

    Gilman, S.; Mazziotta, J.C.

    1989-01-01

    Designed for practicing neurologists and neurosurgeons, this reference focuses on the newest techniques in computed assisted tomography. Text material covers basic principles of computed tomography, as well as the clinical advantages and disadvantages of each modality. The anatomical and/or physiological processes measured by XCT, PET, SPECT and MRI are first discussed in terms of the normal patient, and then applied to the diagnosis and treatment of patients with neurological disease (primarily of the brain). Emphasis is placed on areas of difficult diagnosis, such as differentiating recurrent tumor from radiation necrosis, early diagnosis of dementia, selection of patients for extracranial-intracranial bypass procedures, and localization of epileptic foci.

  20. Biological characteristics and oxidation mechanism of a new manganese-oxidizing bacteria FM-2.

    PubMed

    Tang, Wenwei; Xia, Jin; Zeng, Xinping; Wu, Lujun; Ye, Guoqing

    2014-01-01

    A new manganese-oxidizing strain FM-2 was screened out from biological activated carbon (BAC) filter column and was identified as Citrobacter freundii. The results of the systematic study on this species are as follows: At 27°C, the optimum pH for Citrobacter sp. FM-2 to remove manganese was 7.0-8.0.The best removal rate of manganese under 27°C, pH 7.0 by FM-2 was reached at 4 d, being 76.2%; Compared with adsorption, biological oxidation played a dominant role in this removing process. Almost 75.7% of manganese was oxidized into oxides by Citrobacter sp and there were some particular oxides analogs generated on the bacterial surface; A 296bp DNA fragment amplified from Citrobacter sp. FM-2 revealed that this species has multicopper oxidase genes. Meanwhile, the phylogenetic tree indicated that compared with other related species, Citrobacter sp. FM-2 has its own evolutional independence.

  1. Heat stable antimicrobial activity of Burkholderia gladioli OR1 against clinical drug resistant isolates

    PubMed Central

    Bharti, Pratibha; Anand, Vivek; Chander, Jagdish; Singh, Inder Pal; Singh, Tej Vir; Tewari, Rupinder

    2012-01-01

    Background & objectives: Drug resistant microbes are a serious challenge to human health. During the search for novel antibiotics/inhibitors from the agricultural soil, a bacterial colony was found to inhibit the growth of clinical isolates including Staphylococcus (resistant to amikacin, ciprofloxacin, clindamycin, clinafloxacin, erythromycin, gentamicin and methicillin) and Candida (resistant to fluconazole and itraconazole). The culture was identified as Burkholderia gladioli and produced at least five different antimicrobial compounds which were highly stable at high temperature (121°C) and in the broad pH range (3.0-11.0). We report here the antimicrobial activity of B. gladioli against drug resistant bacterial pathogens. Methods: The bacterial culture was identified using morphological, biochemical and 16S rRNA gene sequencing techniques. The antimicrobial activity of the identified organism against a range of microbial pathogens was checked by Kirby-Bauer's disc diffusion method. The antimicrobial compounds in the cell free supernatant were chloroform-extracted and separated by thin layer chromatography (TLC). Results: B. gladioli OR1 exhibited broad spectrum antimicrobial activity against drug resistant clinical isolates belonging to various genera of bacteria (Staphylococcus, Enterobacter, Enterococcus, Acinetobacter and Citrobacter) and a fungus (Candida). Based on TLC profile and bioautography studies, the chloroform extract of B. gladioli OR1 consisted of at least three anti-staphylococcal and two anti-Candida metabolites. The antimicrobial activity was heat stable (121°C/20 min) as well as pH stable (3.0-11.0). Interpretation & conclusions: The bacterial soil isolate, B. gladioli OR1 possessed the ability to kill various drug resistant bacteria and a fungus. This organism produced many antimicrobial metabolites which might have the potential to be used as antibiotics in future. PMID:22771597

  2. Communal microaerophilic-aerobic biodegradation of Amaranth by novel NAR-2 bacterial consortium.

    PubMed

    Chan, Giek Far; Rashid, Noor Aini Abdul; Chua, Lee Suan; Ab llah, Norzarini; Nasiri, Rozita; Ikubar, Mohamed Roslan Mohamad

    2012-02-01

    A novel bacterial consortium, NAR-2 which consists of Citrobacter freundii A1, Enterococcus casseliflavus C1 and Enterobacter cloacae L17 was investigated for biodegradation of Amaranth azo dye under sequential microaerophilic-aerobic condition. The NAR-2 bacterial consortium with E. casseliflavus C1 as the dominant strain enhanced the decolorization process resulting in reduction of Amaranth in 30 min. Further aerobic biodegradation, which was dominated by C. freundii A1 and E. cloacae L17, allowed biotransformation of azo reduction intermediates and mineralization via metabolic pathways including benzoyl-CoA, protocatechuate, salicylate, gentisate, catechol and cinnamic acid. The presence of autoxidation products which could be metabolized to 2-oxopentenoate was elucidated. The biodegradation mechanism of Amaranth by NAR-2 bacterial consortium was predicted to follow the steps of azo reduction, deamination, desulfonation and aromatic ring cleavage. This is for the first time the comprehensive microaerophilic-aerobic biotransformation pathways of Amaranth dye intermediates by bacterial consortium are being proposed.

  3. Characterization of the Salmonella paratyphi C Vi polysaccharide.

    PubMed Central

    Daniels, E M; Schneerson, R; Egan, W M; Szu, S C; Robbins, J B

    1989-01-01

    The Vi capsular polysaccharide (Vi) is both a virulence factor and a protective antigen of Salmonella typhi; its pathogenic role for Salmonella paratyphi C is less well understood. We found no differences between the antigenic and immunogenic properties and the structure of the Vi from representative strains of S. paratyphi C, S. typhi, and Citrobacter freundii. There were, however, differences in both the amount produced per cell and the degree of association with the cell among the Vi from the three species of Enterobacteriaceae. S. paratyphi C produced less Vi than both the wild-type S. typhi and C. freundii did, and it showed the fastest release of Vi into the media. These findings may provide an explanation for the inability of the Vi to inhibit completely the agglutination of S. paratyphi C by anti-O sera. In an outbreak of enteric fever caused by S. paratyphi C, 66 of 78 isolates (85%) were Vi positive. Images PMID:2506132

  4. Selected emerging diseases of amphibia.

    PubMed

    Latney, La'Toya V; Klaphake, Eric

    2013-05-01

    This review summarizes the most recent updates on emerging infectious diseases of amphibia. A brief summary of Batrachochytrium dendrobatidis history, epidemiology, pathogenesis, life cycle, diagnosis, treatment, and biosecurity is provided. Ambystoma tigrinum virus, common midwife toad virus, frog virus 3, Rana grylio virus, Rana catesbeiana ranavirus, Mahaffey Road virus, Rana esculenta virus, Bohle iridovirus, and tiger frog virus ranaviruses are extensively reviewed. Emerging bacterial pathogens are discussed, including Flavobacter sp, Aeromonas sp, Citrobacter freundii, Chlamydophila sp, Mycobacterium liflandii, Elizabethkingia meningoseptica, and Ochrobactrum anthropi. Rhabdias sp, Ribeiroia sp, and Spirometra erinacei are among several of the parasitic infections overviewed in this article.

  5. Domiciliary cockroaches found in restaurants in five zones of Kuala Lumpur Federal Territory, peninsular Malaysia.

    PubMed

    Jeffery, J; Sulaiman, S; Oothuman, P; Vellayan, S; Zainol-Ariffin, P; Paramaswaran, S; Razak, A; Muslimin, M; Kamil-Ali, O B; Rohela, M; Abdul-Aziz, N M

    2012-03-01

    The following domiciliary cockroaches were collected from restaurants in five zones of Kuala Lumpur Federal Territory, Malaysia using 1L glass beaker traps baited with ground mouse-pellets: Periplaneta americana (Linnaeus) (n = 820), Periplaneta brunnea Burmeister (n = 46), Blattella germanica (Linnaeus) (n = 12504), Supella longipalpa (Fabricius) (n = 321), Symploce pallens Stephens (n = 29) and Neostylopyga rhombifolia (Stoll) (n = 5). The following bacteria were isolated from 10 cockroach specimens: Enterobacter cloacae, Klebsiella pneumoniae ssp. pneumoniae, Klebsiella pneumoniae ssp. rhinoscleromatis and Serratia liquefaciens from 5 B. germanica; Acinetobacter calcoaceticus var. anitratus, Citrobacter diversus/amalonaticus, Escherichia vulneris and K.p. pneumoniae from 3 P. brunnea; and Citrobacter freundii, Enterobacter agglomerans 4, Escherichia adecarboxylate, E. vulneris, K. p. pneumonia, K. p. rhinoscleromatis and Proteus vulgeris from 2 P. americana.

  6. Conservation of DNA sequences for plasmid-mediated citrate utilization within the enterobacteria.

    PubMed

    Hirato, T; Ishiguro, N; Shinagawa, M; Sato, G

    1986-01-01

    Southern blot DNA-DNA hybridization experiments with a cloned Cit+ DNA fragment as a probe showed that the plasmid-mediated Cit+ determinants from four Cit plasmids (R726, pOH3001, pOH3035, and pOH30221) were all homologous. Sequences homologous to the plasmid-borne Cit+ gene were also found in total bacterial DNA isolated from Salmonella paratyphi B, Salmonella enteritidis, Salmonella typhimurium LT-2, Citrobacter freundii, ATCC 8090, Citrobacter amalonaticus ATCC 25405, Klebsiella pneumoniae I and IID 977, and Enterobacter aerogenes ATCC 13048. The DNA digest from C. amalonaticus ATCC 25405 contained a 1.4-kilobase BamHI-HincII DNA fragment that was strongly homologous with and identical in size to the plasmid Cit+ probe.

  7. Clinical professional governance for detailed clinical models.

    PubMed

    Goossen, William; Goossen-Baremans, Anneke

    2013-01-01

    This chapter describes the need for Detailed Clinical Models for contemporary Electronic Health Systems, data exchange and data reuse. It starts with an explanation of the components related to Detailed Clinical Models with a brief summary of knowledge representation, including terminologies representing clinic relevant "things" in the real world, and information models that abstract these in order to let computers process data about these things. Next, Detailed Clinical Models are defined and their purpose is described. It builds on existing developments around the world and accumulates in current work to create a technical specification at the level of the International Standards Organization. The core components of properly expressed Detailed Clinical Models are illustrated, including clinical knowledge and context, data element specification, code bindings to terminologies and meta-information about authors, versioning among others. Detailed Clinical Models to date are heavily based on user requirements and specify the conceptual and logical levels of modelling. It is not precise enough for specific implementations, which requires an additional step. However, this allows Detailed Clinical Models to serve as specifications for many different kinds of implementations. Examples of Detailed Clinical Models are presented both in text and in Unified Modelling Language. Detailed Clinical Models can be positioned in health information architectures, where they serve at the most detailed granular level. The chapter ends with examples of projects that create and deploy Detailed Clinical Models. All have in common that they can often reuse materials from earlier projects, and that strict governance of these models is essential to use them safely in health care information and communication technology. Clinical validation is one point of such governance, and model testing another. The Plan Do Check Act cycle can be applied for governance of Detailed Clinical Models

  8. Mechanisms of ertapenem resistance in Enterobacteriaceae isolates in a tertiary university hospital.

    PubMed

    Chung, Hae-Sun; Yong, Dongeun; Lee, Miae

    2016-06-01

    The aim of this study was to investigate the molecular mechanisms of ertapenem resistance among Enterobacteriaceae isolates in a clinical microbiology laboratory at a tertiary university hospital. A total of 40 clinical isolates including 20 resistant and 20 intermediate isolates were collected from August 2012 to July 2013. Ertapenem susceptibility was confirmed by the broth microdilution method. PCR and sequencing analysis of carbapenemase, AmpC β-lactamase, and extended-spectrum β-lactamase (ESBL) genes were performed. Outer membrane proteins (OMPs) were examined by urea-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Molecular epidemiology studies were performed by pulsed-field gel electrophoresis (PFGE). AmpC β-lactamases and ESBLs were found in 32 (80.0%) and 20 (50.0%) of the 40 isolates with ertapenem non-susceptibility, respectively. Distributions of β-lactamase genes differed among the species. One Citrobacter freundii isolate among the 40 isolates with ertapenem non-susceptibility carrying the blaIMP-1 associated class 1 integron was detected. SDS-PAGE of OMPs showed altered or greatly diminished expression of porins in all isolates of Klebsiella pneumoniae (n=5) and Enterobacter cloacae (n=11) with ertapenem resistance. Porin alterations were less common among the isolates with intermediate susceptibility (4/19). Integration of the results of molecular analysis of β-lactamases and OMP analysis revealed that most of the isolates with ertapenem resistance exhibited β-lactamase activity and porin alteration. PFGE revealed that most isolates were epidemiologically unrelated. Ertapenem resistance in clinical Enterobacteriaceae isolates was associated with β-lactamase activity and porin alteration. Even though carbapenemase-producing Enterobacteriaceae are still rare, continuous monitoring and infection control for carbapenem-resistant Enterobacteriaceae are necessary. PMID:27101841

  9. Being a Clinical Educator

    ERIC Educational Resources Information Center

    Higgs, Joy; Mcallister, Lindy

    2007-01-01

    What is it like to be a clinical educator? How do clinical educators experience and describe their continuing journey of becoming a clinical educator? Within the model developed in this research, dimensions of being a clinical educator were identified. These dimensions include (a) having a sense of self (and the impact of bringing self into the…

  10. Being a clinical educator.

    PubMed

    Higgs, Joy; McAllister, Lindy

    2007-05-01

    What is it like to be a clinical educator? How do clinical educators experience and describe their continuing journey of becoming a clinical educator? Within the model developed in this research, dimensions of being a clinical educator were identified. These dimensions include (a) having a sense of self (and the impact of bringing self into the clinical educator's role), (b) having a sense of relationship with others (and the place of this "interactive self" as a central feature of clinical education), (c) having a sense of being a clinical educator (and how this understanding relates to the previous two dimensions), (d) having a sense of agency (which is vital to the performance of many clinical education roles), (e) seeking dynamic self-congruence, and (e) growth as a clinical educator. This paper presents an overview of the model, discusses its strengths and limitations as a representation of speech pathology clinical educators' experiences, and briefly considers its value for professional development. PMID:17072770

  11. Clinical excellence in cardiology.

    PubMed

    Ziegelstein, Roy C

    2011-08-15

    A recent study identified 7 domains of clinical excellence on the basis of interviews with "clinically excellent" physicians at academic institutions in the United States: (1) communication and interpersonal skills, (2) professionalism and humanism, (3) diagnostic acumen, (4) skillful negotiation of the health care system, (5) knowledge, (6) taking a scholarly approach to clinical practice, and (7) having passion for clinical medicine. What constitutes clinical excellence in cardiology has not previously been defined. The author discusses clinical excellence in cardiology using the framework of these 7 domains and also considers the additional domain of clinical experience. Specific aspects of the domains of clinical excellence that are of greatest relevance to cardiology are highlighted. In conclusion, this discussion characterizes what constitutes clinical excellence in cardiology and should stimulate additional discussion of the topic and an examination of how the domains of clinical excellence in cardiology are related to specific patient outcomes.

  12. Type 3 Muscarinic Receptors Contribute to Clearance of Citrobacter rodentium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although the alpha 7 nicotinic receptor exerts anti-inflammatory effects on immune cells, the role of muscarinic receptors in mucosal homeostasis, response to enteric pathogens, and modulation of immune cell function is undefined. The contribution of type 3 muscarinic receptor (M3R) to mucosal homeo...

  13. Managing clinical grant costs.

    PubMed

    Glass, Harold E; Hollander, Karen

    2009-05-01

    The rapidly increasing cost of pharmaceutical R&D presents a major challenge for the industry. This paper examines one aspect of that spending, clinical grants, and presents ways that pharmaceutical companies can best manage those expenditures. The first part of the paper examines the role of clinical grant payments as a motivation for clinical trial participation. The second part outlines a number of current management practices for controlling clinical grant costs. Financial compensation is an important matter for many physicians conducting clinical trials, especially those in office-based practices and those conducting phase 4 clinical trials. Since financial considerations are important to most types of investigators, and there is no compelling evidence that paying at high rates insures timely performance or quality data, companies engaging clinical investigators must manage their clinical grant funds as effectively as possible. Sound financial management requires that clinical development professionals appreciate the complex relationship between the pharmaceutical company and the physicians who serve as clinical investigators on that company's clinical trials. Sensible financial management of clinical grants also demands that sponsor companies get the most value for their clinical grant spending. Ultimately, good clinical grant management requires an attitude that combines good business sense with an understanding that pharmaceutical R&D strives to bring to market new drugs that can help patient populations around the world. Investigators are medical contractors in clinical trials, and while they are engaged in their vital research, they are a part of the research process that must be carefully budgeted and managed. Society, pharmaceutical companies, clinical investigators, and patients will reap the benefits of adequately budgeted, and well managed clinical grants.

  14. Pathogen-specific effects on milk yield in repeated clinical mastitis episodes in Holstein dairy cows.

    PubMed

    Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

    2014-03-01

    The objective of this study was to estimate the effects of clinical mastitis (CM) cases due to different pathogens on milk yield in Holstein cows. The first 3 CM cases in a cow's lactation were modeled. Eight categories of pathogens were included: Streptococcus spp.; Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level detectable by our microbiological procedures) observed in the culture sample, and cases with contamination (≥ 3 pathogens in the sample); other pathogens that may be treated with antibiotics (included Citrobacter, Corynebacterium bovis, Enterobacter, Enterococcus, Pasteurella, Pseudomonas; "other treatable"); and other pathogens not successfully treated with antibiotics (Trueperella pyogenes, Mycoplasma, Prototheca, yeasts; "other not treatable"). Data from 38,276 lactations in cows from 5 New York State dairy herds, collected from 2003-2004 until 2011, were analyzed. Mixed models with an autoregressive correlation structure (to account for correlation among the repeated measures of milk yield within a lactation) were estimated. Primiparous (lactation 1) and multiparous (lactations 2 and 3) cows were analyzed separately, as the shapes of their lactation curves differed. Primiparas were followed for up to 48 wk of lactation and multiparas for up to 44 wk. Fixed effects included parity, calving season, week of lactation, CM (type, case number, and timing of CM in relation to milk production cycle), and other diseases (milk fever, retained placenta, metritis, ketosis, displaced abomasum). Herd was modeled as a random effect. Clinical mastitis was more common in multiparas than in primiparas. In primiparas, Streptococcus spp. occurred most frequently as the first case. In multiparas, E. coli was most common as the first case. In subsequent cases, CM cases with no specific growth or contamination were most common in both parity groups. The hazard of

  15. Research Areas - Clinical Trials

    Cancer.gov

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  16. Evidence of clinical competence.

    PubMed

    Lejonqvist, Gun-Britt; Eriksson, Katie; Meretoja, Riitta

    2012-06-01

    This cross-sectional research used a qualitative questionnaire to explore clinical competence in nursing. The aim was to look for evidence of how clinical competence showed itself in practice. In the research, the views from both education and working life are combined to broadly explore and describe clinical competence from the perspective of students, clinical preceptors and teachers. The questions were formulated on how clinical competence is characterised and experienced, what contributes to it and how it is maintained, and on the relation between clinical competence and evidence-based care. The answers were analysed by inductive content analysis. The results showed that clinical competence in practice is encountering, knowing, performing, maturing and improving. Clinical competence is an ongoing process, rather than a state and manifests itself in an ontological and a contextual dimension.

  17. Spina Bifida Clinic Directory

    MedlinePlus

    ... Minneapolis Spina Bifida Clinic 2001 Blaisdell Ave. Minneapolis, MN 55404 (952) 993-9100 www.parknicollett.com Shriners ... Clinic (pediatric only) 2025 E. River Parkway Minneapolis, MN 55414 (612) 596-6105 www.twincitiesshrinershospital.org Mayo ...

  18. Clinical ethics revisited

    PubMed Central

    Singer, Peter A; Pellegrino, Edmund D; Siegler, Mark

    2001-01-01

    A decade ago, we reviewed the field of clinical ethics; assessed its progress in research, education, and ethics committees and consultation; and made predictions about the future of the field. In this article, we revisit clinical ethics to examine our earlier observations, highlight key developments, and discuss remaining challenges for clinical ethics, including the need to develop a global perspective on clinical ethics problems. PMID:11346456

  19. Antibiotic resistance in triclosan tolerant fecal coliforms isolated from surface waters near wastewater treatment plant outflows (Morris County, NJ, USA).

    PubMed

    Middleton, June H; Salierno, James D

    2013-02-01

    Triclosan (TCS) is a common antimicrobial agent that has been detected in wastewater treatment plant (WWTP) effluent outflows. A link between TCS exposure and increased antibiotic resistance in microbes has been postulated. The purpose of this study was to evaluate whether fecal coliforms (FC) isolated from surface waters located near (WWTP) outflows display TCS resistance and, if so, whether such organisms exhibit increased resistance to antibiotics. Water samples were collected at two streams in Morris County, NJ that receive WWTP effluent: Loantaka Brook and the Whippany River. Water samples were collected at three sites within each location near the WWTP effluent outflow. Abiotic river parameters were measured and FCs were enumerated for each sample. River parameters were analyzed to determine if TCS or antibiotic resistance was correlated to water quality. Triclosan resistance levels were determined for individual isolates, and isolates were screened against seven classes of antibiotics at clinically relevant levels to assess cross-resistance. At Loantaka Brook, 78.8% of FC isolates were resistant to TCS with an average minimum inhibitory concentration (MIC) of 43.2 μg ml(-1). In addition, 89.6% of isolates were resistant to four classes of antibiotics and all were identified as Citrobacter freundii. There was a significant effect of stream location on mean TCS MIC values in the Loantaka Brook, with effluent isolates maintaining significantly higher MIC values compared to upstream isolates. At Whippany River sites, TCS resistant isolates were detected on 94% of sampling dates with a significant relationship between TCS resistance and multiple antibiotic resistances (≥ three antibiotic classes, p<0.001). TCS resistant isolates were significantly more resistant to chloramphenicol (p=0.007) and to nitrofurantoin (p=0.037) when compared to TCS sensitive isolates. Environmental FC isolates resistant to high level TCS included species of Escherichia, Enterobacter

  20. Antibiotic resistance in triclosan tolerant fecal coliforms isolated from surface waters near wastewater treatment plant outflows (Morris County, NJ, USA).

    PubMed

    Middleton, June H; Salierno, James D

    2013-02-01

    Triclosan (TCS) is a common antimicrobial agent that has been detected in wastewater treatment plant (WWTP) effluent outflows. A link between TCS exposure and increased antibiotic resistance in microbes has been postulated. The purpose of this study was to evaluate whether fecal coliforms (FC) isolated from surface waters located near (WWTP) outflows display TCS resistance and, if so, whether such organisms exhibit increased resistance to antibiotics. Water samples were collected at two streams in Morris County, NJ that receive WWTP effluent: Loantaka Brook and the Whippany River. Water samples were collected at three sites within each location near the WWTP effluent outflow. Abiotic river parameters were measured and FCs were enumerated for each sample. River parameters were analyzed to determine if TCS or antibiotic resistance was correlated to water quality. Triclosan resistance levels were determined for individual isolates, and isolates were screened against seven classes of antibiotics at clinically relevant levels to assess cross-resistance. At Loantaka Brook, 78.8% of FC isolates were resistant to TCS with an average minimum inhibitory concentration (MIC) of 43.2 μg ml(-1). In addition, 89.6% of isolates were resistant to four classes of antibiotics and all were identified as Citrobacter freundii. There was a significant effect of stream location on mean TCS MIC values in the Loantaka Brook, with effluent isolates maintaining significantly higher MIC values compared to upstream isolates. At Whippany River sites, TCS resistant isolates were detected on 94% of sampling dates with a significant relationship between TCS resistance and multiple antibiotic resistances (≥ three antibiotic classes, p<0.001). TCS resistant isolates were significantly more resistant to chloramphenicol (p=0.007) and to nitrofurantoin (p=0.037) when compared to TCS sensitive isolates. Environmental FC isolates resistant to high level TCS included species of Escherichia, Enterobacter

  1. Identification and inhibition of histamine-forming bacteria in blue scad (Decapterus maruadsi) and chub mackerel (Scomber japonicus).

    PubMed

    Hu, Jia-Wei; Cao, Min-Jie; Guo, Shun-Cai; Zhang, Ling-Jing; Su, Wen-Jin; Liu, Guang-Ming

    2015-02-01

    In this study, we investigated the differences in histamine accumulation between blue scad and chub mackerel and methods of inhibiting histamine-forming bacteria and controlling histamine accumulation in fish. The free histidine contents in blue scad and chub mackerel were 1.45 and 2.75 mg/g, respectively. The histamine-forming bacteria isolated from them were identified as Citrobacter freundii, Citrobacter braakii, and Enterobacter aerogenes using 16S rDNA sequence analysis, the VITEK 2 Compact system, and MALDI-TOF MS. The histamine-producing capacities of C. freundii, C. braakii, and E. aerogenes were 470, 1,057, and 4,213 mg/liter, respectively, after culture at 37°C for 48 h. Among the different antimicrobials and preservatives tested, potassium sorbate and sodium diacetate effectively inhibited the histamine-forming bacteria and their histamine production. After chub mackerel was dipped into 0.5% potassium sorbate or sodium diacetate, its histamine content increased more slowly at room temperature. Therefore, a potassium sorbate or sodium diacetate dipping treatment could effectively control histamine accumulation in fish. PMID:25710155

  2. Identification and inhibition of histamine-forming bacteria in blue scad (Decapterus maruadsi) and chub mackerel (Scomber japonicus).

    PubMed

    Hu, Jia-Wei; Cao, Min-Jie; Guo, Shun-Cai; Zhang, Ling-Jing; Su, Wen-Jin; Liu, Guang-Ming

    2015-02-01

    In this study, we investigated the differences in histamine accumulation between blue scad and chub mackerel and methods of inhibiting histamine-forming bacteria and controlling histamine accumulation in fish. The free histidine contents in blue scad and chub mackerel were 1.45 and 2.75 mg/g, respectively. The histamine-forming bacteria isolated from them were identified as Citrobacter freundii, Citrobacter braakii, and Enterobacter aerogenes using 16S rDNA sequence analysis, the VITEK 2 Compact system, and MALDI-TOF MS. The histamine-producing capacities of C. freundii, C. braakii, and E. aerogenes were 470, 1,057, and 4,213 mg/liter, respectively, after culture at 37°C for 48 h. Among the different antimicrobials and preservatives tested, potassium sorbate and sodium diacetate effectively inhibited the histamine-forming bacteria and their histamine production. After chub mackerel was dipped into 0.5% potassium sorbate or sodium diacetate, its histamine content increased more slowly at room temperature. Therefore, a potassium sorbate or sodium diacetate dipping treatment could effectively control histamine accumulation in fish.

  3. University cardiology clinic.

    PubMed

    Borozanov, V

    2013-01-01

    In distant 1972, within framework of the Internal Clinic, a cardiologic department was organized which was soon, on 29.XII.1974, transformed into the Cardiology Clinic, later the Institute for Heart Diseases, and in 2008 was renamed the University Cardiology Clinic. The greater part of its foundation was possible owing to Prof. Dimitar Arsov and Prof. Radovan Percinkovski, who was the clinic's first director in the period from 1974 to 1984. In 1985, the Clinic moved into its own new building, and in that way was physically detached from the Internal Clinics. Until its move to the new building, the Clinic functioned in the Internal Clinics building, organized as an outpatient polyclinic and inpatient infirmary department with clinical beds, a coronary intensive care unit and a haemodynamics laboratory equipped with the most modern equipment of that time. Today the Clinic functions through two integral divisions: an inpatient infirmary department which comprises an intensive coronary care unit and fourteen wards which altogether have 139 clinical beds, and the diagnostic centre which comprises an emergency clinic and day hospital, a communal and consultative outpatients' clinic functioning on a daily basis, through which some 300-350 patients pass every day, and diagnostic laboratories with a capacity of nearly 100 non-invasive and 20-30 invasive diagnostic procedures daily. The Clinic is a teaching base, and its doctors are educators of students at the Medical, Dental and Pharmacy Faculties, and also of students at the High School for Nurses and X-ray technicians, but also for those in Internal Medicine and especially Cardiology. The Clinic is also a base for scientific Masters' and post-doctoral studies, and such higher degrees are achieved not only by doctors who work here, but also by doctors from Medical Centres both in the country and abroad. Doctors working in this institution publish widely, not only a great number of books and monographs, but also original

  4. University cardiology clinic.

    PubMed

    Borozanov, V

    2013-01-01

    In distant 1972, within framework of the Internal Clinic, a cardiologic department was organized which was soon, on 29.XII.1974, transformed into the Cardiology Clinic, later the Institute for Heart Diseases, and in 2008 was renamed the University Cardiology Clinic. The greater part of its foundation was possible owing to Prof. Dimitar Arsov and Prof. Radovan Percinkovski, who was the clinic's first director in the period from 1974 to 1984. In 1985, the Clinic moved into its own new building, and in that way was physically detached from the Internal Clinics. Until its move to the new building, the Clinic functioned in the Internal Clinics building, organized as an outpatient polyclinic and inpatient infirmary department with clinical beds, a coronary intensive care unit and a haemodynamics laboratory equipped with the most modern equipment of that time. Today the Clinic functions through two integral divisions: an inpatient infirmary department which comprises an intensive coronary care unit and fourteen wards which altogether have 139 clinical beds, and the diagnostic centre which comprises an emergency clinic and day hospital, a communal and consultative outpatients' clinic functioning on a daily basis, through which some 300-350 patients pass every day, and diagnostic laboratories with a capacity of nearly 100 non-invasive and 20-30 invasive diagnostic procedures daily. The Clinic is a teaching base, and its doctors are educators of students at the Medical, Dental and Pharmacy Faculties, and also of students at the High School for Nurses and X-ray technicians, but also for those in Internal Medicine and especially Cardiology. The Clinic is also a base for scientific Masters' and post-doctoral studies, and such higher degrees are achieved not only by doctors who work here, but also by doctors from Medical Centres both in the country and abroad. Doctors working in this institution publish widely, not only a great number of books and monographs, but also original

  5. Assessing clinical pragmatism.

    PubMed

    Jansen, Lynn A

    1998-03-01

    "Clinical pragmatism" is an important new method of moral problem-solving in clinical practice. This method draws on the pragmatic philosophy of John Dewey and recommends an experimental approach to solving moral problems in clinical practice. Although the method may shed some light on how clinicians and their patients ought to interact when moral problems are at hand, it nonetheless is deficient in a number of respects. Clinical pragmatism fails to explain adequately how moral poblems can be solved experimentally, it underestimates the relevance and importance of judgment in clinical ethics, and it presents a questionable account of the role that moral principles should play in moral problem solving.

  6. Genetic Characterization of Carbapenem-Resistant Enterobacteriaceae and the Spread of Carbapenem-Resistant Klebsiella pneumonia ST340 at a University Hospital in Thailand.

    PubMed

    Netikul, Thidarat; Kiratisin, Pattarachai

    2015-01-01

    Carbapenem-resistant Enterobacteriaceae (CRE) has increasingly spread worldwide in the past decade. The prevalence and characteristics of CRE in Thailand are unknown. In this study, we conducted a 2-year surveillance of CRE among 12,741 clinical isolates of Enterobacteriaceae at the largest university hospital in Thailand with molecular characterization of beta-lactamase (bla) genes, including carbapenemase genes. The CRE prevalence was 1.4%. blaKPC-13 and blaIMP-14a were the only carbapenemase genes detected among these CRE isolates. blaKPC-13 gene was found in a single isolate of Escherichia coli, Enterobacter cloacae and Citrobacter freundii, and blaIMP-14a was found in four isolates of Klebsiella pneumoniae. Carbapenem-resistant K. pneumoniae (CRKP) isolates were resistant to multiple carbapenems at a higher ratio than other CRE species, and thus were further characterized for resistance phenotypes, bla genotypes and molecular epidemiology. Most CRKP isolates harboured multiple bla genes, especially those related to extended-spectrum beta-lactamases. Seven CRKP isolates were resistant to all tested carbapenems, and showed decreased ompK35 and/or ompK36 porin gene expression. Molecular typing of CRKP based on pulsed-field gel electrophoresis (PFGE) demonstrated several unrelated clones. Multilocus sequence typing (MLST) was partially concordant with PFGE results and revealed that ST340, a member of drug-resistant K. pneumoniae clonal complex 258, was the most predominant clone, followed by ST48, ST11 and ST273. The novel ST1645 was identified from this study. ST340 has neither been shown to be predominated among CRKP from other studies, nor been reported in Thailand. Therefore, it emphases a critical concern to monitor and control the spread of CRKP. PMID:26407326

  7. Genetic Characterization of Carbapenem-Resistant Enterobacteriaceae and the Spread of Carbapenem-Resistant Klebsiella pneumonia ST340 at a University Hospital in Thailand

    PubMed Central

    Netikul, Thidarat; Kiratisin, Pattarachai

    2015-01-01

    Carbapenem-resistant Enterobacteriaceae (CRE) has increasingly spread worldwide in the past decade. The prevalence and characteristics of CRE in Thailand are unknown. In this study, we conducted a 2-year surveillance of CRE among 12,741 clinical isolates of Enterobacteriaceae at the largest university hospital in Thailand with molecular characterization of beta-lactamase (bla) genes, including carbapenemase genes. The CRE prevalence was 1.4%. blaKPC-13 and blaIMP-14a were the only carbapenemase genes detected among these CRE isolates. blaKPC-13 gene was found in a single isolate of Escherichia coli, Enterobacter cloacae and Citrobacter freundii, and blaIMP-14a was found in four isolates of Klebsiella pneumoniae. Carbapenem-resistant K. pneumoniae (CRKP) isolates were resistant to multiple carbapenems at a higher ratio than other CRE species, and thus were further characterized for resistance phenotypes, bla genotypes and molecular epidemiology. Most CRKP isolates harboured multiple bla genes, especially those related to extended-spectrum beta-lactamases. Seven CRKP isolates were resistant to all tested carbapenems, and showed decreased ompK35 and/or ompK36 porin gene expression. Molecular typing of CRKP based on pulsed-field gel electrophoresis (PFGE) demonstrated several unrelated clones. Multilocus sequence typing (MLST) was partially concordant with PFGE results and revealed that ST340, a member of drug-resistant K. pneumoniae clonal complex 258, was the most predominant clone, followed by ST48, ST11 and ST273. The novel ST1645 was identified from this study. ST340 has neither been shown to be predominated among CRKP from other studies, nor been reported in Thailand. Therefore, it emphases a critical concern to monitor and control the spread of CRKP. PMID:26407326

  8. Molecular Characterization of Klebsiella pneumoniae Carbapenemase (KPC)-Producing Enterobacteriaceae in Ontario, Canada, 2008-2011

    PubMed Central

    Tijet, Nathalie; Sheth, Prameet M.; Lastovetska, Olga; Chung, Catherine; Patel, Samir N.; Melano, Roberto G.

    2014-01-01

    Due to the lack of detailed reports of Klebsiella pneumoniae carbapenemase (KPC)-producing enterobacteria in Ontario, Canada, we perform a molecular characterization of KPC-producing Enterobacteriaceae submitted to the provincial reference laboratory from 2008 to 2011. Susceptibility profiles were accessed by E-test. Molecular types of isolates were determined by pulse-field gel electrophoresis (PFGE) and multilocus sequence typing. Screening of ß-lactamase genes was performed by multiplex PCR and alleles were identified by DNA sequencing. The genetic platform of blaKPC gene was analyzed by PCR. Plasmid replicons were typed using PCR-based typing approach. KPC-plasmids were also evaluated by S1 nuclease-PFGE and Southern blot. Thirty unique clinical isolates (26 Klebsiella pneumoniae, 2 Enterobacter cloacae, 1 Citrobacter freundii and 1 Raoultella ornithinolytica) were identified as blaKPC positive: 4 in 2008, 3 in 2009, 10 in 2010 and 13 in 2011. The majority exhibited resistance to carbapenems, cephalosporins and fluoroquinolones and two isolates were also resistant to colistin. The isolates harbored blaKPC-2 (n = 23) or blaKPC-3 (n = 7). blaTEM-1 (n = 27) was commonly detected and occasionally blaOXA-1 (n = 3) and blaCTX-M-15 (n = 1). As expected, all K. pneumoniae isolates carried blaSHV-11. blaKPC genes were identified on Tn4401a (n = 20) or b (n = 10) isoforms, on plasmids of different sizes belonging to the incompatibility groups IncFIIA (n = 19), IncN (n = 3), IncI2 (n = 3), IncFrep (n = 2) and IncA/C (n = 1). The occurrence of KPC ß-lactamase in Ontario was mainly associated with the spread of the K. pneumoniae clone ST258. PMID:25549365

  9. Travel-Related Carbapenemase-Producing Gram-Negative Bacteria in Alberta, Canada: the First 3 Years

    PubMed Central

    Peirano, Gisele; Ahmed-Bentley, Jasmine; Fuller, Jeff; Rubin, Joseph E.

    2014-01-01

    We describe here the characteristics of Alberta, Canada, patients with infections or colonizations with carbapenemase-producing Gram-negative bacteria during 2010 to 2013 that were linked to recent travel outside Canada. Antimicrobial susceptibility was determined by broth microdilution, and isolates were characterized using PCR, sequencing, and multilocus sequencing typing. A broth mating study was used to assess the transferability of resistance plasmids, which were subsequently characterized. All the patients (n = 12) included in our study had contact with a health care system while abroad. Most of the patients presented with urinary tract infections (UTIs) and were admitted to hospitals within weeks after their return to Alberta. Secondary spread occurred in 1 case, resulting in the death of another patient. The carbapenemase-producing bacteria (n = 17) consisted of Escherichia coli (sequence type 101 [ST101], ST365, ST405, and ST410) with NDM-1, Klebsiella pneumoniae (ST15, ST16, ST147, ST258, ST340, ST512, and ST972) with NDM-1, OXA-181, KPC-2, and KPC-3, Acinetobacter baumannii with OXA-23, Providencia rettgeri with NDM-1, Enterobacter cloacae with KPC-2, and Citrobacter freundii with NDM-1. The blaNDM-1 gene was associated with various narrow- (i.e., IncF) and broad- (i.e., IncA/C and IncL/M) host-range plasmids with different addiction factors. Our results show that NDM-producing K. pneumoniae, belonging to a variety of sequence types with different plasmid scaffolds, are regularly imported from India into Alberta. Clinical microbiology laboratories should remain vigilant in detecting bacteria with carbapenemases. PMID:24599977

  10. Molecular characterization of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae in Ontario, Canada, 2008-2011.

    PubMed

    Tijet, Nathalie; Sheth, Prameet M; Lastovetska, Olga; Chung, Catherine; Patel, Samir N; Melano, Roberto G

    2014-01-01

    Due to the lack of detailed reports of Klebsiella pneumoniae carbapenemase (KPC)-producing enterobacteria in Ontario, Canada, we perform a molecular characterization of KPC-producing Enterobacteriaceae submitted to the provincial reference laboratory from 2008 to 2011. Susceptibility profiles were accessed by E-test. Molecular types of isolates were determined by pulse-field gel electrophoresis (PFGE) and multilocus sequence typing. Screening of ß-lactamase genes was performed by multiplex PCR and alleles were identified by DNA sequencing. The genetic platform of blaKPC gene was analyzed by PCR. Plasmid replicons were typed using PCR-based typing approach. KPC-plasmids were also evaluated by S1 nuclease-PFGE and Southern blot. Thirty unique clinical isolates (26 Klebsiella pneumoniae, 2 Enterobacter cloacae, 1 Citrobacter freundii and 1 Raoultella ornithinolytica) were identified as blaKPC positive: 4 in 2008, 3 in 2009, 10 in 2010 and 13 in 2011. The majority exhibited resistance to carbapenems, cephalosporins and fluoroquinolones and two isolates were also resistant to colistin. The isolates harbored blaKPC-2 (n = 23) or blaKPC-3 (n = 7). blaTEM-1 (n = 27) was commonly detected and occasionally blaOXA-1 (n = 3) and blaCTX-M-15 (n = 1). As expected, all K. pneumoniae isolates carried blaSHV-11. blaKPC genes were identified on Tn4401a (n = 20) or b (n = 10) isoforms, on plasmids of different sizes belonging to the incompatibility groups IncFIIA (n = 19), IncN (n = 3), IncI2 (n = 3), IncFrep (n = 2) and IncA/C (n = 1). The occurrence of KPC ß-lactamase in Ontario was mainly associated with the spread of the K. pneumoniae clone ST258. PMID:25549365

  11. Molecular characterization of class b carbapenemases in advanced stage of dissemination and emergence of class d carbapenemases in Enterobacteriaceae from Croatia.

    PubMed

    Bedenić, Branka; Sardelić, Sanda; Luxner, Josefa; Bošnjak, Zrinka; Varda-Brkić, Dijana; Lukić-Grlić, Amarela; Mareković, Ivana; Frančula-Zaninović, Sonja; Krilanović, Marija; Šijak, Dorotea; Grisold, Andrea; Zarfel, Gernot

    2016-09-01

    Carbapenemases involved in acquired carbapenem resistance in Enterobacteriaceae belong to Ambler class A serin β-lactamases, class B metallo-β-lactamases (MBL) or class D OXA-48-like β-lactamases. The aim of the present study was to analyse the molecular epidemiology and the mechanisms and routes of spread of class B and class D carbapenemases in Croatia. In total 68 isolates were analyzed. Antibiotic susceptibility was determined by broth microdilution method. PCR was used to detect antibiotic-resistance genes. Genotyping was performed by rep-PCR and MLST. Sixty-five isolates were found to harbour VIM-1 carbapenemase, seven of which were positive also for NDM-1, while two strains harboured only NDM-1. OXA-48 was detected in three isolates, two of which coproduced VIM-1. Thirty-six strains possessed additional CTX-M-15 β-lactamase whereas 64 were positive for TEM-1. CMY was found in 18 Citrobacter freundii isolates and DHA-1 in one Enterobacter cloacae isolate. Four different plasmid-incompatibility groups were found: A/C, L/M, N and FIIAs. Unlike C. freundii and E. cloacae, Klebsiella pneumoniae showed high diversity of rep-PCR patterns. E. cloacae and C. freundii predominantly belonged to one large clone which was allocated to ST105 and ST24, respectively. Three different types of carbapenemases were identified showing the complexity of CRE in Croatia.

  12. Copper-resistant enteric bacteria from United Kingdom and Australian piggeries.

    PubMed Central

    Williams, J R; Morgan, A G; Rouch, D A; Brown, N L; Lee, B T

    1993-01-01

    Thirty-three enteric isolates from Australian (Escherichia coli only) and United Kingdom (U.K.) (Salmonella sp., Citrobacter spp., and E. coli) piggeries were characterized with respect to their copper resistance. The copper resistance phenotypes of four new Australian E. coli isolates were comparable with that of the previously studied E. coli K-12 strain ED8739(pRJ1004), in that the resistance level in rich media was high (up to 18 mM CuSO4) and resistance was inducible. Copper resistance was transferable by conjugation from the new Australian isolates to E. coli K-12 recipients. DNA similarity between the new Australian isolates and the pco copper resistance determinant located on plasmid pRJ1004 was strong as measured by DNA-DNA hybridization; however, the copper resistance plasmids were nonidentical as indicated by the presence of restriction fragment length polymorphisms between the plasmids. DNA-DNA hybridization and polymerase chain reaction analysis demonstrated DNA homology between the pco determinant and DNA from the U.K.E. coli, Salmonella sp., and Citrobacter freundii isolates. However, the copper resistance level and inducibility were variable among the U.K. strains. Of the U.K. E. coli isolates, 1 demonstrated a high level of copper resistance, 4 exhibited intermediate resistance, and 16 showed a low level of copper resistance; all of these resistances were expressed constitutively. A single U.K. C. freundii isolate, had a high level of copper resistance, inducible by subtoxic levels of copper. Transconjugants from one E. coli and one C. freundii donor, with E. coli K-12 strain UB1637 as a recipient, showed copper resistance levels and inducibility of resistance which differed from that expressed from plasmid pRJ1004.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8368840

  13. Aerobic Bacterial Community of American Cockroach Periplaneta americana,a Step toward Finding Suitable Paratransgenesis Candidates

    PubMed Central

    Akbari, Sanaz; Oshaghi, Mohammad Ali; Hashemi-Aghdam, Saedeh Sadat; Hajikhani, Sara; Oshaghi, Ghazaleh; Shirazi, Mohammad Hasan

    2015-01-01

    Background: Cockroaches mechanically spread pathogenic agents, however, little is known about their gut microbiota. Identification of midgut microbial community helps targeting novel biological control strategies such as paratransgenesis. Here the bacterial microbiota of Periplaneta americana midgut, were identified and evaluated for finding proper paratransgenesis candidate. Methods: Midgut of specimens were dissected and cultivated in different media. The bacterial isolates were then identified using the phenotypic and 16S-rRNA sequencing methods. Results: The analytical profile index (API) kit showed presence of 11 bacterial species including: Escherichia coli, Shigella flexineri, Citrobacter freundii, E. vulneris, Enterobacter cloacae, Yersinia pseudotuberculosis, Y. intermedia, Leclericia adecarboxylata, Klebsiella oxytoca, K. planticola, and Rahnella aquatilis in the cockroach midguts. The first three species are potentially symbiotic whereas others are transient. The conventional plating method revealed presence of only four isolates of Salmonella, E. coli, and Proteus which in three cases mismatched with API and 16S-rRNA genotyping. The API correctly identified the four isolates as Shigella flexneri, Citrobacter freundii, and E. coli (n= 2). 16S-rRNA sequence analysis confirmed the API results; however the C. freundii sequence was identical with C. murliniae indicating lack of genetic variation in the gene between these two closely related species. Conclusion: A low number of potentially symbiotic bacteria were found in the American cockroach midguts. Among them Enterobacter cloacae is a potential candidate for paratransgenesis approach whereas other bacteria are pathogens and are not useful for the approach. Data analysis showed that identification levels increase from the conventional to API and to genotyping respectively. PMID:26114142

  14. Development of clinical sites.

    PubMed

    O'Brien, Mary

    2015-02-01

    Clinical experiences are vital to all types of healthcare educational programs. Supervised clinical experiences provide the opportunity for the learner to apply didactic knowledge and theory to real world situations and hone skills necessary for entry into practice. Nurse anesthesia programs utilize a wide variety of clinical sites to expose student registered nurse anesthetists to experiences that will prepare them clinically, academically and professionally to enter practice as a Certified Registered Nurse Anesthetist. This article describes the process of developing a clinical site. A thorough evaluation will determine the types of experiences meant to be offered at the site, the resources available to house and educate the students, and how to evaluate the effectiveness of the clinical site. Open communication between the clinical coordinator and the program director or designee is essential to ensure success of the clinical site. The Council on Accreditation of Nurse Anesthesia Educational Programs has resources available to guide those interested in becoming a clinical site, as well as for program administrators who seek to add new experiences to their programs. PMID:25842629

  15. Student Health Clinics.

    ERIC Educational Resources Information Center

    Jelliffe, James H.; Schipp, Michael K.

    2002-01-01

    Discusses important issues concerning the design of student health clinics, including convenient access, privacy and security, showers and sinks, durability and safety, and special considerations. (EV)

  16. The NASA Clinic System

    NASA Technical Reports Server (NTRS)

    Scarpa, Philip J.; Williams, Richard

    2009-01-01

    NASA maintains on site occupational health clinics at all Centers and major facilities NASA maintains an on-site clinic that offers comprehensive health care to astronauts at the Johnson Space Center NASA deploys limited health care capability to space and extreme environments Focus is always on preventive health care

  17. Clinical Application of Electrocardiography.

    ERIC Educational Resources Information Center

    Brammell, H. L.; Orr, William

    The scalar electrocardiogram (ECG) is one of the most important and commonly used clinical tools in medicine. A detailed description of the recordings of cardiac electrical activity made by the ECG is presented, and the vast numbers of uses made with the data provided by this diagnostic tool are cited. Clinical applications of the ECG are listed.…

  18. Building clinical pathways.

    PubMed

    Leininger, S M

    1998-01-01

    TQM principles change the work environment so that point-of-service personnel can improve health care delivery to patients. The clinical pathway process starts with the principles of TQM. In the era of managed care, health care resources can be managed effectively using a clinical pathway. The multidisciplinary team has the opportunity to improve the health care services provided to patients.

  19. Clinical implementation of pharmacogenetics.

    PubMed

    García-González, Xandra; Cabaleiro, Teresa; Herrero, María José; McLeod, Howard; López-Fernández, Luis A

    2016-03-01

    In the last decade, pharmacogenetic research has been performed in different fields. However, the application of pharmacogenetic findings to clinical practice has not been as fast as desirable. The current situation of clinical implementation of pharmacogenetics is discussed. This review focuses on the advances of pharmacogenomics to individualize cancer treatments, the relationship between pharmacogenetics and pharmacodynamics in the clinical course of transplant patients receiving a combination of immunosuppressive therapy, the needs and barriers facing pharmacogenetic clinical application, and the situation of pharmacogenetic testing in Spain. It is based on lectures presented by speakers of the Clinical Implementation of Pharmacogenetics Symposium at the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held in April 20, 2015. PMID:26751902

  20. Situated clinical cognition.

    PubMed

    Timpka, T

    1995-10-01

    The features characterizing study of clinical cognition in situ are formulated as: Re-cognition of context, culture, history and affect. Socializing and phenomenalistic elements are again included in the research agenda. Interest for representations: an analysis level is reserved for the symbols, rules and images relevant to define in models of clinical cognition. De-emphasis on computer modeling: investigations focus on the 'functional systems' in which computers are involved. Rootedness in classical philosophical problems: issues concerning situated clinical cognition are connected to the width of available theoretical literature. Belief in interdisciplinary studies: productive interactions between the new and traditional disciplines is anticipated, implying that new shared methods have to be developed. When scientific perspectives are broadened, a new balance has to be found between the relevance of the subject of study and methodological rigor. The situated clinical cognition framework is to allow for moving between models, theories, and perspectives, as it does not presuppose a singular model of clinical thinking.

  1. [Bioethics in clinical practice].

    PubMed

    Sánchez-Gonzaléz, Miguel; Herreros, Benjamín

    2015-01-01

    Bioethics has grown exponentially in recent decades. Its most important schools include principlism, casuistry, virtue ethics and the ethics of care. These schools are not exclusive. Within bioethics, clinical ethics addresses the inherent clinical practice ethical problems, problems which are many and very varied. Bioethics training is essential for clinicians to address these bioethics' problems. But even the professionals are trained, there are problems that cannot be solved individually and require advisory groups in clinical ethics: clinical ethics committees. These committees are also responsible for education in bioethics in health institutions. Clinical bioethics is a practical discipline, oriented to address specific problems, so its development is necessary to improve the decision making in such complex problems, inevitable problems in healthcare.

  2. In the clinic. Insomnia.

    PubMed

    Masters, Philip A

    2014-10-01

    This issue provides a clinical overview of Insomnia focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.

  3. Clinical Pathway for Thyroidectomy.

    PubMed

    Villar del Moral, Jesús María; Soria Aledo, Víctor; Colina Alonso, Alberto; Flores Pastor, Benito; Gutiérrez Rodríguez, María Teresa; Ortega Serrano, Joaquín; Parra Hidalgo, Pedro; Ros López, Susana

    2015-05-01

    Clinical pathways are care plans applicable to patient care procedures that present variations in practice and a predictable clinical course. They are designed not as a substitute for clinical judgment, but rather as a means to improve the effectiveness and efficiency of the procedures. This clinical pathway is the result of a collaborative work of the Sections of Endocrine Surgery and Quality Management of the Spanish Association of Surgeons. It attempts to provide a framework for standardizing the performance of thyroidectomy, the most frequently performed operation in endocrine surgery. Along with the usual documents of clinical pathways (temporary matrix, variance tracking and information sheets, assessment indicators and a satisfaction questionnaire) it includes a review of the scientific evidence around different aspects of pre, intra and postoperative management. Among others, antibiotic and antithrombotic prophylaxis, preoperative preparation in hyperthyroidism, intraoperative neuromonitoring and systems for obtaining hemostasis are included, along with management of postoperative hypocalcemia. PMID:25732107

  4. Clinical Pathway for Thyroidectomy.

    PubMed

    Villar del Moral, Jesús María; Soria Aledo, Víctor; Colina Alonso, Alberto; Flores Pastor, Benito; Gutiérrez Rodríguez, María Teresa; Ortega Serrano, Joaquín; Parra Hidalgo, Pedro; Ros López, Susana

    2015-05-01

    Clinical pathways are care plans applicable to patient care procedures that present variations in practice and a predictable clinical course. They are designed not as a substitute for clinical judgment, but rather as a means to improve the effectiveness and efficiency of the procedures. This clinical pathway is the result of a collaborative work of the Sections of Endocrine Surgery and Quality Management of the Spanish Association of Surgeons. It attempts to provide a framework for standardizing the performance of thyroidectomy, the most frequently performed operation in endocrine surgery. Along with the usual documents of clinical pathways (temporary matrix, variance tracking and information sheets, assessment indicators and a satisfaction questionnaire) it includes a review of the scientific evidence around different aspects of pre, intra and postoperative management. Among others, antibiotic and antithrombotic prophylaxis, preoperative preparation in hyperthyroidism, intraoperative neuromonitoring and systems for obtaining hemostasis are included, along with management of postoperative hypocalcemia.

  5. Clinical Research Methodology 2: Observational Clinical Research.

    PubMed

    Sessler, Daniel I; Imrey, Peter B

    2015-10-01

    Case-control and cohort studies are invaluable research tools and provide the strongest feasible research designs for addressing some questions. Case-control studies usually involve retrospective data collection. Cohort studies can involve retrospective, ambidirectional, or prospective data collection. Observational studies are subject to errors attributable to selection bias, confounding, measurement bias, and reverse causation-in addition to errors of chance. Confounding can be statistically controlled to the extent that potential factors are known and accurately measured, but, in practice, bias and unknown confounders usually remain additional potential sources of error, often of unknown magnitude and clinical impact. Causality-the most clinically useful relation between exposure and outcome-can rarely be definitively determined from observational studies because intentional, controlled manipulations of exposures are not involved. In this article, we review several types of observational clinical research: case series, comparative case-control and cohort studies, and hybrid designs in which case-control analyses are performed on selected members of cohorts. We also discuss the analytic issues that arise when groups to be compared in an observational study, such as patients receiving different therapies, are not comparable in other respects.

  6. Clinical Microbiology Informatics

    PubMed Central

    Sintchenko, Vitali; Rauch, Carol A.; Pantanowitz, Liron

    2014-01-01

    SUMMARY The clinical microbiology laboratory has responsibilities ranging from characterizing the causative agent in a patient's infection to helping detect global disease outbreaks. All of these processes are increasingly becoming partnered more intimately with informatics. Effective application of informatics tools can increase the accuracy, timeliness, and completeness of microbiology testing while decreasing the laboratory workload, which can lead to optimized laboratory workflow and decreased costs. Informatics is poised to be increasingly relevant in clinical microbiology, with the advent of total laboratory automation, complex instrument interfaces, electronic health records, clinical decision support tools, and the clinical implementation of microbial genome sequencing. This review discusses the diverse informatics aspects that are relevant to the clinical microbiology laboratory, including the following: the microbiology laboratory information system, decision support tools, expert systems, instrument interfaces, total laboratory automation, telemicrobiology, automated image analysis, nucleic acid sequence databases, electronic reporting of infectious agents to public health agencies, and disease outbreak surveillance. The breadth and utility of informatics tools used in clinical microbiology have made them indispensable to contemporary clinical and laboratory practice. Continued advances in technology and development of these informatics tools will further improve patient and public health care in the future. PMID:25278581

  7. Clinical microbiology informatics.

    PubMed

    Rhoads, Daniel D; Sintchenko, Vitali; Rauch, Carol A; Pantanowitz, Liron

    2014-10-01

    The clinical microbiology laboratory has responsibilities ranging from characterizing the causative agent in a patient's infection to helping detect global disease outbreaks. All of these processes are increasingly becoming partnered more intimately with informatics. Effective application of informatics tools can increase the accuracy, timeliness, and completeness of microbiology testing while decreasing the laboratory workload, which can lead to optimized laboratory workflow and decreased costs. Informatics is poised to be increasingly relevant in clinical microbiology, with the advent of total laboratory automation, complex instrument interfaces, electronic health records, clinical decision support tools, and the clinical implementation of microbial genome sequencing. This review discusses the diverse informatics aspects that are relevant to the clinical microbiology laboratory, including the following: the microbiology laboratory information system, decision support tools, expert systems, instrument interfaces, total laboratory automation, telemicrobiology, automated image analysis, nucleic acid sequence databases, electronic reporting of infectious agents to public health agencies, and disease outbreak surveillance. The breadth and utility of informatics tools used in clinical microbiology have made them indispensable to contemporary clinical and laboratory practice. Continued advances in technology and development of these informatics tools will further improve patient and public health care in the future.

  8. Design of clinical trials.

    PubMed

    Rollo, David; Machado, Sanjay; Ceschin, Mauro

    2010-09-01

    Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports.

  9. Design of clinical trials.

    PubMed

    Rollo, David; Machado, Sanjay; Ceschin, Mauro

    2010-09-01

    Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports. PMID:20674592

  10. Mindfulness and clinical psychology.

    PubMed

    Childs, David

    2011-09-01

    Does mindfulness offer more to psychology than a useful therapeutic technique? This paper argues that it can also establish a state of presence which is understood in relation to the practice of phenomenology. Mindfulness is then both linked to a Western intellectual tradition and offers that tradition a systematic method. This is an opening for psychological investigation of the non-conceptual basis of everyday experience. The combination of this theoretical stance with the increasingly widespread practical training of clinical psychologists in mindfulness has broad implications for clinical practice; this is illustrated in relation to the descriptive approach to clinical problems, qualitative research, and reflective practice.

  11. Alagille syndrome: clinical perspectives.

    PubMed

    Saleh, Maha; Kamath, Binita M; Chitayat, David

    2016-01-01

    Alagille syndrome is an autosomal dominant, complex multisystem disorder characterized by the presence of three out of five major clinical criteria: cholestasis with bile duct paucity on liver biopsy, congenital cardiac defects (with particular involvement of the pulmonary arteries), posterior embryotoxon in the eye, characteristic facial features, and butterfly vertebrae. Renal and vascular abnormalities can also occur. Inter- and intrafamilial variabilities in the clinical manifestations are common. We reviewed the clinical features and management as well as the molecular basis of Alagille syndrome. PMID:27418850

  12. Alagille syndrome: clinical perspectives

    PubMed Central

    Saleh, Maha; Kamath, Binita M; Chitayat, David

    2016-01-01

    Alagille syndrome is an autosomal dominant, complex multisystem disorder characterized by the presence of three out of five major clinical criteria: cholestasis with bile duct paucity on liver biopsy, congenital cardiac defects (with particular involvement of the pulmonary arteries), posterior embryotoxon in the eye, characteristic facial features, and butterfly vertebrae. Renal and vascular abnormalities can also occur. Inter- and intrafamilial variabilities in the clinical manifestations are common. We reviewed the clinical features and management as well as the molecular basis of Alagille syndrome. PMID:27418850

  13. [Midwifery clinical practicum education].

    PubMed

    Kao, Chien-Huei; Gau, Meei-Ling

    2013-06-01

    Midwifery is a practical facet of the health sciences that emphasizes professional competence-oriented teaching and learning. Cognitive and practical processes integrate and build midwifery student professional knowledge, attitudes, and skills. Clinical education is a teaching method and strategy used to prepare midwifery students for professional practice. Midwifery clinical teaching plans are designed using literature review, expert opinions, and student comments and determine total required hours and caseloads. Midwifery clinical teaching activities and methods promote self-reflection, childbirth education fundamentals, learning by role model observation, and learning role function through overseas observership programs. This paper discusses midwifery education dilemmas and coping methods in Taiwan.

  14. Automation in Clinical Microbiology

    PubMed Central

    Ledeboer, Nathan A.

    2013-01-01

    Historically, the trend toward automation in clinical pathology laboratories has largely bypassed the clinical microbiology laboratory. In this article, we review the historical impediments to automation in the microbiology laboratory and offer insight into the reasons why we believe that we are on the cusp of a dramatic change that will sweep a wave of automation into clinical microbiology laboratories. We review the currently available specimen-processing instruments as well as the total laboratory automation solutions. Lastly, we outline the types of studies that will need to be performed to fully assess the benefits of automation in microbiology laboratories. PMID:23515547

  15. Clinical ethics committee.

    PubMed Central

    Thornton, J. G.; Lilford, R. J.

    1995-01-01

    An informal clinical ethics committee was set up to advise on ethical problems in prenatal diagnosis in Leeds. It was used twice in six months but was not called on again in the subsequent year, and we describe this experience. In North America similar committees are often used to advise on clinical moral dilemmas, and we review the published evidence from there and discuss some of the advantages and problems. Our committee's advice may have altered clinicians' actions considerably, but perhaps doctors in Britain are not yet ready to surrender this aspect of clinical autonomy. PMID:7549638

  16. Antibacterial activity of silver-doped hydroxyapatite nanoparticles against gram-positive and gram-negative bacteria

    NASA Astrophysics Data System (ADS)

    Ciobanu, Carmen Steluta; Iconaru, Simona Liliana; Le Coustumer, Phillippe; Constantin, Liliana Violeta; Predoi, Daniela

    2012-06-01

    Ag-doped nanocrystalline hydroxyapatite nanoparticles (Ag:HAp-NPs) (Ca10- x Ag x (PO4)6(OH)2, x Ag = 0.05, 0.2, and 0.3) with antibacterial properties are of great interest in the development of new products. Coprecipitation method is a promising route for obtaining nanocrystalline Ag:HAp with antibacterial properties. X-ray diffraction identified HAp as an unique crystalline phase in each sample. The calculated lattice constants of a = b = 9.435 Å, c = 6.876 Å for x Ag = 0.05, a = b = 9.443 Å, c = 6.875 Å for x Ag = 0.2, and a = b = 9.445 Å, c = 6.877 Å for x Ag = 0.3 are in good agreement with the standard of a = b = 9.418 Å, c = 6.884 Å (space group P63/m). The Fourier transform infrared and Raman spectra of the sintered HAp show the absorption bands characteristic to hydroxyapatite. The Ag:HAp nanoparticles are evaluated for their antibacterial activity against Staphylococcus aureus, Klebsiella pneumoniae, Providencia stuartii, Citrobacter freundii and Serratia marcescens. The results showed that the antibacterial activity of these materials, regardless of the sample types, was greatest against S. aureus, K. pneumoniae, P. stuartii, and C. freundii. The results of qualitative antibacterial tests revealed that the tested Ag:HAp-NPs had an important inhibitory activity on P. stuartii and C. freundii. The absorbance values measured at 490 nm of the P. stuartii and C. freundii in the presence of Ag:HAp-NPs decreased compared with those of organic solvent used (DMSO) for all the samples ( x Ag = 0.05, 0.2, and 0.3). Antibacterial activity increased with the increase of x Ag in the samples. The Ag:HAp-NP concentration had little influence on the bacterial growth ( P. stuartii).

  17. Clinical specular microscopy

    SciTech Connect

    Hirst, L.W.; Laing, R.A.

    1987-01-01

    This book provides the general ophthalmologist with a guide to the clinical applications of specular microscopy. Important material is included on laser injury, cataract surgery, corneal transplants, glaucoma, uveitis, and trauma.

  18. Understanding Clinical Alarm Safety.

    PubMed

    Lukasewicz, Carol L; Mattox, Elizabeth Andersson

    2015-08-01

    Patient safety organizations and health care accreditation agencies recognize the significance of clinical alarm hazards. The Association for the Advancement of Medical Instrumentation, a nonprofit organization focused on development and use of safe and effective medical equipment, identifies alarm management as a major issue for health care organizations. ECRI Institute, a nonprofit organization that researches approaches for improving patient safety and quality of care, identifies alarm hazards as the most significant of the "Top Ten Health Technology Hazards" for 2014. A new Joint Commission National Patient Safety Goal focusing on clinical alarm safety contains new requirements for accredited hospitals to be fully implemented by 2016. Through a fictional unfolding case study, this article reviews selected contributing factors to clinical alarm hazards present in inpatient, high-acuity settings. Understanding these factors improves contributions by nurses to clinical alarm safety practice.

  19. [Carbohydrates in clinical nutrition].

    PubMed

    Lysikov, Iu A

    2013-01-01

    The article presents data on role of carbohydrate in clinical nutrition. The review described carbohydrate metabolism, hormonal regulation of carbohydrate, carbohydrate energy source role, carbohydrate requirements in critical study.

  20. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  1. Learn about Clinical Studies

    MedlinePlus

    ... in the care of future patients by providing information about the benefits and risks of therapeutic, preventative, or diagnostic products or interventions. Clinical trials provide the basis for the development and marketing of new drugs, biological products, and medical devices. ...

  2. Clinical Trials - Participants

    MedlinePlus

    ... participating in was reviewed by an IRB. Further Reading For more information about research protections, see: Office ... data and decide whether the results have medical importance. Results from clinical trials are often published in ...

  3. The clinical skills unit.

    PubMed Central

    Bligh, J.

    1995-01-01

    Clinical skills units offer exciting and innovative ways of learning about clinical skills. Links between theoretical knowledge and clinical practice are appropriate for both undergraduate and postgraduate training. Students and doctors can practice and acquire technical and examination skills in a standardised and protected environment without being concerned about the distress such learning may cause real patients. Models and simulators used in skills units are being developed to keep pace with demand, with a corresponding increase in standards of quality and durability. As undergraduate medical courses respond to the demands of modern clinical practice the use of such facilities will increase. This paper describes the functions of skills units and provides practical examples of educational strategies in use. Images p731-a p731-b p731-c p731-d PMID:8552536

  4. Defining clinical 'workstation'.

    PubMed

    Safran, C

    1994-01-01

    Interest in the physician's workstation has increased, yet often seems to focus on technological issues. At Boston's Beth Israel Hospital, the Center for Clinical Computing includes heavily used clinical workstations. Their evolution over the past 20 years suggests design criteria: the workstation must be patient-centered, the interface must be uniform, and data acquisition must be addressed at a system level. However, it is clinical function that really defines a workstation. The workstation should do the following: display patient information rapidly and flexibly; assist with administrative tasks; facilitate communication; and provide four important types of decision support: access to literature, access to databases, clinical calculation, and 'synthetic vision,' or different views of patient data. The solutions to our healthcare problems are not in 'workboxes' we can buy, but in creative approaches we can imagine. We need a patient-centered infrastructure and a reduced workload for the clinician-perhaps a 'worklesstation'. PMID:8125637

  5. Find a Free Clinic

    MedlinePlus

    ... Dental, Medical, Rx's www.amissionofmercy.org A Storehouse Free. Medical Ministries 675 E Lexington Rd Mocksville , NC ... E-mail: Info@nafcclinics.org National Association of Free & Charitable Clinics © 2016

  6. Clinical excellence in pediatrics.

    PubMed

    Mote, Phillip C; Solomon, Barry S; Wright, Scott M; Crocetti, Michael

    2014-08-01

    The 7 core domains of clinical excellence in academic medicine, as defined by the Miller-Coulson Academy of Clinical Excellence at Johns Hopkins, are applicable to the field of pediatrics. The authors use published case reports and teaching models from the pediatric literature to illustrate how thoughtful clinicians have realized distinction in each of the 7 clinical excellence domains, recognizing excellent pediatric patient care serves to strengthen all 3 arms of the tripartite academic mission. Clinicians who feel valued by their institution may be more likely to remain in an academic clinical setting, where they promote the health and well-being of their patients, provide support to families and caregivers, serve as role models for pediatric trainees, and integrate research into their practice with the overall aim of improving patient outcomes.

  7. An obesity clinic model.

    PubMed

    Munnelly, Patricia; Feehan, S

    2002-02-01

    The high incidence of obesity in Ireland is of growing concern. The Irish Universities Nutrition Alliance North/South Food Consumption Survey found that 18 % of the population are obese and 39% overweight. Obesity and overweight increase the risk of developing CHD, type 2 diabetes, hypertension and some forms of cancer. It is well accepted that the best treatment for obesity is a combination of energy intake reduction and regular exercise. Previously, dietary compliance has been shown to improve when monitored on a regular basis. The lengthy delay between clinic visits to the dietitian has been reported by those who failed to lose weight to be the main reason for poor compliance. A weight monitoring clinic was designed to offer those requiring regular support and encouragement the opportunity to monitor their weights on a more regular basis, while waiting for their return visit to the dietitian in the Outpatient Departments. As resources were limited, an efficient use of time was essential. The clinic design was: 1 h/week; eight to fourteen appointments per clinic; weekly or fortnightly visit; return patients only. The clinic was started on a trial basis in June 1999, and was evaluated in December 2000. Referrals were only taken from other dietitians, and each participant was informed in advance of the necessity of having a return Outpatient Department appointment for full dietary review. Forty-eight participants attended more than three times up to and including December 2000 (seven males, forty-one females). The number of clinic visits ranged from three to twenty-eight. Mean weight at start of clinic was 92.94 kg. Of the group attending, 67 % (thirty-two) successfully lost weight and maintained this weight loss. This ranged from 0.1 kg to 23.5 kg. While in total 31% (fifteen) of attendees had gained weight at December 2000, all attendees, including this fifteen, had lost weight at some point during the clinic. Self-reported reasons given for weight regain

  8. Heritable unilateral clinical anophthalmia.

    PubMed

    Griepentrog, Gregory J; Lucarelli, Mark J

    2004-03-01

    We examined a newborn child with unilateral right-sided clinical anophthalmos born to a mother with unilateral left-sided anophthalmos. Although rare, isolated nonsyndromic heritable unilateral anophthalmia and microphthalmia have been reported in the literature. We briefly review the genetics of such anomalies and discuss the importance of a full clinical genetics evaluation. Treatment of this patient's anophthalmic socket consists of progressive conformer expansion to be followed by placement of a self-inflating polymer expander.

  9. MTA: A Clinical Review

    PubMed Central

    Tawil, Peter Z; Duggan, Derek J.; Galicia, Johnah C.

    2016-01-01

    MTA has been a revolutionary material in endodontics. Since it’s introduction in the 1990’s several studies have demonstrated its use in several clinical applications. MTA has been extensively studied and is currently used for perforation repairs, apexifications, regenerative procedures, apexogenesis, pulpotomies & pulp capping. This article will review the history, composition, research findings and clinical applications of this versatile material. PMID:25821936

  10. Clinical careers film.

    PubMed

    2015-09-01

    Those interested in developing clinical academic careers might be interested in a short animated film by Health Education England (HEE) and the National Institute for Health Research. The three-minute film, a frame from which is shown below, describes the sort of opportunities that are on offer to all professionals as part of the HEE's clinical academic careers framework. You can view the film on YouTube at tinyurl.com/pelb95c. PMID:26309005

  11. Pre-Clinical Lupus

    PubMed Central

    Bourn, Rebecka; James, Judith A.

    2015-01-01

    Purpose of review Systemic lupus erythematosus (SLE) is often preceded by immune dysregulation and clinical manifestations below the threshold for SLE classification. This review discusses current and evolving concepts about the pre-classification period of SLE, including clinical and mechanistic observations, and potential avenues for early identification and intervention. Recent findings Although incomplete lupus erythematosus (ILE) involves fewer clinical manifestations than SLE, ILE can cause organ damage and mortality. Common clinical features in ILE include antinuclear antibody seropositivity, polyarthritis, immunologic manifestations, and hematological disorders. Despite having lower disease activity and damage scores than SLE patients, ILE patients may develop pulmonary arterial hypertension or renal, neurological, or peripheral vascular damage. The recently proposed SLICC SLE classification criteria could shift the period considered “preclinical SLE”. Murine studies suggest that the balance of T helper/T regulatory cells, peroxisome proliferator-activated receptor γ activity, and plasmacytoid dendritic cell pathways may be valuable targets for early intervention. Summary Advances in our understanding of early SLE, including stages before clinical features are fully developed, will improve our ability to identify individuals at high risk of classification for potential prevention trials, provide necessary information to improve diagnostic testing, and perhaps identify novel targets for directed therapeutics in clinical SLE. PMID:26125103

  12. Good Clinical Practice Training

    PubMed Central

    Arango, Jaime; Chuck, Tina; Ellenberg, Susan S.; Foltz, Bridget; Gorman, Colleen; Hinrichs, Heidi; McHale, Susan; Merchant, Kunal; Shapley, Stephanie; Wild, Gretchen

    2016-01-01

    Good Clinical Practice (GCP) is an international standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials. The goal of GCP is to ensure the protection of the rights, integrity, and confidentiality of clinical trial participants and to ensure the credibility and accuracy of data and reported results. In the United States, trial sponsors generally require investigators to complete GCP training prior to participating in each clinical trial to foster GCP and as a method to meet regulatory expectations (ie, sponsor’s responsibility to select qualified investigators per 21 CFR 312.50 and 312.53(a) for drugs and biologics and 21 CFR 812.40 and 812.43(a) for medical devices). This training requirement is often extended to investigative site staff, as deemed relevant by the sponsor, institution, or investigator. Those who participate in multiple clinical trials are often required by sponsors to complete repeated GCP training, which is unnecessarily burdensome. The Clinical Trials Transformation Initiative convened a multidisciplinary project team involving partners from academia, industry, other researchers and research staff, and government to develop recommendations for streamlining current GCP training practices. Recommendations drafted by the project team, including the minimum key training elements, frequency, format, and evidence of training completion, were presented to a broad group of experts to foster discussion of the current issues and to seek consensus on proposed solutions. PMID:27390628

  13. How Do Clinical Trials Work?

    MedlinePlus

    ... Trials Clinical Trial Websites How Do Clinical Trials Work? If you take part in a clinical trial, ... kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...

  14. The clinical trial.

    PubMed

    Chalmers, T C

    1981-01-01

    This paper argues that scientific clinical trials are the most ethical way to benefit patients whenever there is uncertainty about proper diagnosis and therapy. An increasing number of trials reported in clinical journals have employed randomization since the 1st extensive use of randomized controlled trials after the 2nd World War. A review of 4 examples of the response of physicians to trial results that differ from their own opinions indicates considerable reluctance to accept the results, no matter how well the trials were designed. Such reluctance may gradually disappear as physicians become better educated in clinical trial methodology. A good trial requires that unconscious bias be controlled, that data be recorded in detail and expertly analyzed, and that the sample size be considered when interpreting the results. Procedures designed to handle the ethical issues related to clinical trials include peer review, informed consent, initiation of randomization with the 1st use of a new therapy, reference to the previous outcomes in protocols and informed consent procedures and deferring decisions about when to stop studies to 3rd parties (such as data monitoring committees or policy advisory boards) and avoiding the use of placebos when an effective therapy is known. It is recommended that money for clinical trials be provided from the general medical care budget rather than the 2% that is devoted to all biomedical research.

  15. Clinical immunity to malaria.

    PubMed

    Schofield, Louis; Mueller, Ivo

    2006-03-01

    Under appropriate conditions of transmission intensity, functional immunity to malaria appears to be acquired in distinct stages. The first phase reduces the likelihood of severe or fatal disease; the second phase limits the clinical impact of 'mild' malaria; and the third provides partial but incomplete protection against pathogen burden. These findings suggest clinical immunity to mortality and morbidity is acquired earlier, with greater ease, and via distinct mechanisms as compared to anti-parasite immunity, which is more difficult to achieve, takes longer and is only ever partially efficacious. The implications of this view are significant in that current vaccination strategies aim predominantly to achieve anti-parasite immunity, although imparting clinical immunity is the public health objective. Despite enormous relevance for global public health, the mechanisms governing these processes remain obscure. Four candidate mechanisms might mediate clinical immunity, namely immunity to cytoadherence determinants, tolerance to toxins, acquired immunity to toxins, and immunoregulation. This review addresses the targets and determinants of clinical immunity, and considers the implications for vaccine development.

  16. Clinical Pharmacogenetics Implementation

    PubMed Central

    WEITZEL, KRISTIN W.; ELSEY, AMANDA R.; LANGAEE, TAIMOUR Y.; BURKLEY, BENJAMIN; NESSL, DAVID R.; OBENG, ANIWAA OWUSU; STALEY, BENJAMIN J.; DONG, HUI-JIA; ALLAN, ROBERT W.; LIU, J. FELIX; COOPER-DEHOFF, RHONDA M.; ANDERSON, R. DAVID; CONLON, MICHAEL; CLARE-SALZLER, MICHAEL J.; NELSON, DAVID R.; JOHNSON, JULIE A.

    2014-01-01

    Current challenges exist to widespread clinical implementation of genomic medicine and pharmacogenetics. The University of Florida (UF) Health Personalized Medicine Program (PMP) is a pharmacist-led, multidisciplinary initiative created in 2011 within the UF Clinical Translational Science Institute. Initial efforts focused on pharmacogenetics, with long-term goals to include expansion to disease-risk prediction and disease stratification. Herein we describe the processes for development of the program, the challenges that were encountered and the clinical acceptance by clinicians of the genomic medicine implementation. The initial clinical implementation of the UF PMP began in June 2012 and targeted clopidogrel use and the CYP2C19 genotype in patients undergoing left heart catheterization and percutaneous-coronary intervention (PCI). After 1 year, 1,097 patients undergoing left heart catheterization were genotyped preemptively, and 291 of those underwent subsequent PCI. Genotype results were reported to the medical record for 100% of genotyped patients. Eighty patients who underwent PCI had an actionable genotype, with drug therapy changes implemented in 56 individuals. Average turnaround time from blood draw to genotype result entry in the medical record was 3.5 business days. Seven different third party payors, including Medicare, reimbursed for the test during the first month of billing, with an 85% reimbursement rate for outpatient claims that were submitted in the first month. These data highlight multiple levels of success in clinical implementation of genomic medicine. PMID:24616371

  17. Neonatal clinical pharmacology

    PubMed Central

    Allegaert, Karel; van de Velde, Marc; van den Anker, John

    2013-01-01

    Effective and safe drug administration in neonates should be based on integrated knowledge on the evolving physiological characteristics of the infant who will receive the drug, and the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. Consequently, clinical pharmacology in neonates is as dynamic and diverse as the neonates we admit to our units while covariates explaining the variability are at least as relevant as median estimates. The unique setting of neonatal clinical pharmacology will be highlighted based on the hazards of simple extrapolation of maturational drug clearance when only based on ‘adult’ metabolism (propofol, paracetamol). Secondly, maturational trends are not at the same pace for all maturational processes. This will be illustrated based on the differences between hepatic and renal maturation (tramadol, morphine, midazolam). Finally, pharmacogenetics should be tailored to neonates, not just mirror adult concepts. Because of this diversity, clinical research in the field of neonatal clinical pharmacology is urgently needed, and facilitated through PK/PD modeling. In addition, irrespective of already available data to guide pharmacotherapy, pharmacovigilance is needed to recognize specific side effects. Consequently, paediatric anesthesiologists should consider to contribute to improved pharmacotherapy through clinical trial design and collaboration, as well as reporting on adverse effects of specific drugs. PMID:23617305

  18. Gait analysis: clinical facts.

    PubMed

    Baker, Richard; Esquenazi, Alberto; Benedetti, Maria G; Desloovere, Kaat

    2016-08-01

    Gait analysis is a well-established tool for the quantitative assessment of gait disturbances providing functional diagnosis, assessment for treatment planning, and monitoring of disease progress. There is a large volume of literature on the research use of gait analysis, but evidence on its clinical routine use supports a favorable cost-benefit ratio in a limited number of conditions. Initially gait analysis was introduced to clinical practice to improve the management of children with cerebral palsy. However, there is good evidence to extend its use to patients with various upper motor neuron diseases, and to lower limb amputation. Thereby, the methodology for properly conducting and interpreting the exam is of paramount relevance. Appropriateness of gait analysis prescription and reliability of data obtained are required in the clinical environment. This paper provides an overview on guidelines for managing a clinical gait analysis service and on the principal clinical domains of its application: cerebral palsy, stroke, traumatic brain injury and lower limb amputation. PMID:27618499

  19. Clinical Protocol Information System

    PubMed Central

    Wirtschafter, David D.; Gams, Richard; Ferguson, Carol; Blackwell, William; Boackle, Paul

    1980-01-01

    The Clinical Protocol Information System (CPIS) supports the clinical research and patient care objectives of the SouthEastern Cancer Study Group (SEG). The information system goals are to improve the evaluability of clinical trials, decrease the frequency of adverse patient events, implement drug toxicity surveillance, improve the availability of study data and demonstrate the criteria for computer networks that can impact on the general medical care of the community. Nodes in the network consist of Data General MicroNova MP-100 minicomputers that drive the interactive data dialogue and communicate with the network concentrator (another DG MicroNova) in Birmingham. Functions supported include: source data editing, care “advice,” care “audit,” care “explanation,” and treatment note printing. The complete database is updated nightly and resides on UAB's IBM 370/158-AP.

  20. [Management of clinical nutrition].

    PubMed

    Martín Folgueras, Tomás

    2015-05-07

    Proper management of Clinical Nutrition requires careful planning of the resources required to delineate the activities to be performed by each of the participants and consider the need for continued evaluation of the results to improve. Units of Nutrition and Nutritional Support Teams must have a multidisciplinary composition, incorporating professionals with training and experience in Clinical Nutrition. Whenever conditions permit and activity of each center indicates, the staff's dedication to nutrition must be complete. The organization of processes and use of clinical practice protocols facilitates the monitoring of the activities carried out by teams of Nutrition. Each stage of a process has quality criteria based on scientific knowledge, and some key objectives whose degree of achievement can be measured by monitoring quality indicators and their comparison with standards. Successive cycles of measurement indicators, evaluation and corrective interventions lead to continuous process improvement.

  1. [Terminology in clinical bioethics].

    PubMed

    Herreros, Benjamín; Moreno-Milán, Beatriz; Pacho-Jiménez, Eloy; Real de Asua, Diego; Roa-Castellanos, Ricardo Andrés; Valentia, Emanuele

    2015-01-01

    In this article some of the most relevant terms in clinical bioethics are defined. The terms were chosen based on three criteria: impact on the most important problems in clinical bioethics, difficulty in understanding, and need to clarify their meaning. For a better understanding, the terms were grouped into 5 areas: general concepts (conflict of values, deliberation, conflict of interest, conscientious objection); justice (justice, distributive justice, models of justice, triage); clinical matters (information, competency, capability, informed consent, mature minor, coercion, secrecy, privacy, confidentiality, professional secrecy); end of life (prior instructions, limitation of therapeutic efforts, professional obstinacy, futility, palliative care, palliative sedation, principle of double effect, euthanasia, assisted suicide, persistent vegetative state, minimally conscious state, locked-in syndrome, brain death), and beginning of life (assisted reproduction, genetic counseling, preimplantation genetic diagnosis).

  2. Sense and clinical sensibility.

    PubMed

    Billow, Richard M

    2013-10-01

    I call attention to the metapsychology of sense, and the role sense plays-phenomenologically and symbolically-in the life of the clinician and the group. Each group member asserts influence in taking a role as the perceiver and the perceived, the senser and the sensed. We reach for sense, for without sense reference, we cannot grasp or even talk about psychic reality. It serves as sign and symbol, as metaphor, analogy, illustration, and model. Sense fixes experience yet may fixate experience and interfere with developing abstract thoughts. Clinical vignettes illustrate how the leader may utilize his or her particular clinical sensibility to reach the group and focus attention, to link sense to psychic qualities: to the personality of the members, the group culture and process, and the live clinical interaction. PMID:24004010

  3. Pediatric Anthrax Clinical Management

    PubMed Central

    Bradley, John S.; Peacock, Georgina; Krug, Steven E.; Bower, William A.; Cohn, Amanda C.; Meaney-Delman, Dana; Pavia, Andrew T.

    2015-01-01

    Anthrax is a zoonotic disease caused by Bacillus anthracis, which has multiple routes of infection in humans, manifesting in different initial presentations of disease. Because B anthracis has the potential to be used as a biological weapon and can rapidly progress to systemic anthrax with high mortality in those who are exposed and untreated, clinical guidance that can be quickly implemented must be in place before any intentional release of the agent. This document provides clinical guidance for the prophylaxis and treatment of neonates, infants, children, adolescents, and young adults up to the age of 21 (referred to as “children”) in the event of a deliberate B anthracis release and offers guidance in areas where the unique characteristics of children dictate a different clinical recommendation from adults. PMID:24777226

  4. Pediatric anthrax clinical management.

    PubMed

    Bradley, John S; Peacock, Georgina; Krug, Steven E; Bower, William A; Cohn, Amanda C; Meaney-Delman, Dana; Pavia, Andrew T

    2014-05-01

    Anthrax is a zoonotic disease caused by Bacillus anthracis, which has multiple routes of infection in humans, manifesting in different initial presentations of disease. Because B anthracis has the potential to be used as a biological weapon and can rapidly progress to systemic anthrax with high mortality in those who are exposed and untreated, clinical guidance that can be quickly implemented must be in place before any intentional release of the agent. This document provides clinical guidance for the prophylaxis and treatment of neonates, infants, children, adolescents, and young adults up to the age of 21 (referred to as "children") in the event of a deliberate B anthracis release and offers guidance in areas where the unique characteristics of children dictate a different clinical recommendation from adults.

  5. Consolidated clinical microbiology laboratories.

    PubMed

    Sautter, Robert L; Thomson, Richard B

    2015-05-01

    The manner in which medical care is reimbursed in the United States has resulted in significant consolidation in the U.S. health care system. One of the consequences of this has been the development of centralized clinical microbiology laboratories that provide services to patients receiving care in multiple off-site, often remote, locations. Microbiology specimens are unique among clinical specimens in that optimal analysis may require the maintenance of viable organisms. Centralized laboratories may be located hours from patient care settings, and transport conditions need to be such that organism viability can be maintained under a variety of transport conditions. Further, since the provision of rapid results has been shown to enhance patient care, effective and timely means for generating and then reporting the results of clinical microbiology analyses must be in place. In addition, today, increasing numbers of patients are found to have infection caused by pathogens that were either very uncommon in the past or even completely unrecognized. As a result, infectious disease specialists, in particular, are more dependent than ever on access to high-quality diagnostic information from clinical microbiology laboratories. In this point-counterpoint discussion, Robert Sautter, who directs a Charlotte, NC, clinical microbiology laboratory that provides services for a 40-hospital system spread over 3 states in the southeastern United States explains how an integrated clinical microbiology laboratory service has been established in a multihospital system. Richard (Tom) Thomson of the NorthShore University HealthSystem in Evanston, IL, discusses some of the problems and pitfalls associated with large-scale laboratory consolidation.

  6. Toward transparent clinical policies.

    PubMed

    Shiffman, Richard N; Marcuse, Edgar K; Moyer, Virginia A; Neuspiel, Daniel R; Hodgson, Elizabeth Susan; Glade, Gordon; Harbaugh, Norman; Miller, Marlene R; Sevilla, Xavier; Simpson, Lisa; Takata, Glenn

    2008-03-01

    Clinical policies of professional societies such as the American Academy of Pediatrics are valued highly, not only by clinicians who provide direct health care to children but also by many others who rely on the professional expertise of these organizations, including parents, employers, insurers, and legislators. The utility of a policy depends, in large part, on the degree to which its purpose and basis are clear to policy users, an attribute known as the policy's transparency. This statement describes the critical importance and special value of transparency in clinical policies, guidelines, and recommendations; helps identify obstacles to achieving transparency; and suggests several approaches to overcome these obstacles.

  7. Pharmacogenomics in the clinic

    PubMed Central

    Relling, Mary V.; Evans, William E.

    2015-01-01

    Preface After decades of discovery, inherited variation in approximately 20 genes affecting about 80 medications has been identified as actionable in the clinic. Additional somatically acquired genomic variants direct the choice of “targeted” anticancer drugs for individual patients. Current efforts that focus on the processes required to appropriately act on pharmacogenomic variability in the clinic are systematically moving pharmacogenomics from discovery to implementation as an evidenced-based strategy for improving the use of medications, thereby providing an important cornerstone for precision medicine. PMID:26469045

  8. Pharmacogenomics in the clinic.

    PubMed

    Relling, Mary V; Evans, William E

    2015-10-15

    After decades of discovery, inherited variations have been identified in approximately 20 genes that affect about 80 medications and are actionable in the clinic. And some somatically acquired genetic variants direct the choice of 'targeted' anticancer drugs for individual patients. Current efforts that focus on the processes required to appropriately act on pharmacogenomic variability in the clinic are moving away from discovery and towards implementation of an evidenced-based strategy for improving the use of medications, thereby providing a cornerstone for precision medicine.

  9. Hypomagnesemia: a clinical perspective

    PubMed Central

    Pham, Phuong-Chi T; Pham, Phuong-Anh T; Pham, Son V; Pham, Phuong-Truc T; Pham, Phuong-Mai T; Pham, Phuong-Thu T

    2014-01-01

    Although magnesium is involved in a wide spectrum of vital functions in normal human physiology, the significance of hypomagnesemia and necessity for its treatment are under-recognized and underappreciated in clinical practice. In the current review, we first present an overview of the clinical significance of hypomagnesemia and normal magnesium metabolism, with a focus on renal magnesium handling. Subsequently, we review the literature for both congenital and acquired hypomagnesemic conditions that affect the various steps in normal magnesium metabolism. Finally, we present an approach to the routine evaluation and suggested management of hypomagnesemia. PMID:24966690

  10. Genetic Tests:Clinical Validity and Clinical Utility

    PubMed Central

    Burke, Wylie

    2014-01-01

    When evaluating the appropriate use of new genetic tests, clinicians and health care policymakers must consider the accuracy with which a test identifies a patient’s clinical status (clinical validity) and the risks and benefits resulting from test use (clinical utility). Genetic tests in current use vary in accuracy and potential to improve health outcomes, and these test properties may be influenced by testing technology and the clinical setting in which the test is used. This unit defines clinical validity and clinical utility, provides examples, and considers the implications of these test properties for clinical practice. PMID:24763995

  11. Clinical reasoning of nursing students on clinical placement: Clinical educators' perceptions.

    PubMed

    Hunter, Sharyn; Arthur, Carol

    2016-05-01

    Graduate nurses may have knowledge and adequate clinical psychomotor skills however they have been identified as lacking the clinical reasoning skills to deliver safe, effective care suggesting contemporary educational approaches do not always facilitate the development of nursing students' clinical reasoning. While nursing literature explicates the concept of clinical reasoning and develops models that demonstrate clinical reasoning, there is very little published about nursing students and clinical reasoning during clinical placements. Semi-structured interviews were conducted with ten clinical educators to gain an understanding of how they recognised, developed and appraised nursing students' clinical reasoning while on clinical placement. This study found variability in the clinical educators' conceptualisation, recognition, and facilitation of students' clinical reasoning. Although most of the clinical educators conceptualised clinical reasoning as a process those who did not demonstrated the greatest variability in the recognition and facilitation of students' clinical reasoning. The clinical educators in this study also described being unable to adequately appraise a student's clinical reasoning during clinical placement with the use of the current performance assessment tool.

  12. Clinical reasoning of nursing students on clinical placement: Clinical educators' perceptions.

    PubMed

    Hunter, Sharyn; Arthur, Carol

    2016-05-01

    Graduate nurses may have knowledge and adequate clinical psychomotor skills however they have been identified as lacking the clinical reasoning skills to deliver safe, effective care suggesting contemporary educational approaches do not always facilitate the development of nursing students' clinical reasoning. While nursing literature explicates the concept of clinical reasoning and develops models that demonstrate clinical reasoning, there is very little published about nursing students and clinical reasoning during clinical placements. Semi-structured interviews were conducted with ten clinical educators to gain an understanding of how they recognised, developed and appraised nursing students' clinical reasoning while on clinical placement. This study found variability in the clinical educators' conceptualisation, recognition, and facilitation of students' clinical reasoning. Although most of the clinical educators conceptualised clinical reasoning as a process those who did not demonstrated the greatest variability in the recognition and facilitation of students' clinical reasoning. The clinical educators in this study also described being unable to adequately appraise a student's clinical reasoning during clinical placement with the use of the current performance assessment tool. PMID:27235568

  13. ClinicalAccess: a clinical decision support tool.

    PubMed

    Crowell, Karen; Vardell, Emily

    2015-01-01

    ClinicalAccess is a new clinical decision support tool that uses a question-and-answer format to mirror clinical decision-making strategies. The unique format of ClinicalAccess delivers concise, authoritative answers to more than 120,000 clinical questions. This column presents a review of the product, a sample search, and a comparison with other point-of-care search engines.

  14. Clinical Trials: CSDRG Overview

    ERIC Educational Resources Information Center

    Logemann, Jeri A.

    2004-01-01

    Recent importance placed upon efficacy research has spawned the development of the Communication Sciences and Disorders Clinical Trials Research Group (CSDRG). This group, funded by the National Institutes of Health (NIH), was organized by the American Speech Language and Hearing Association to address the need for more treatment efficacy research…

  15. Computerized Clinical Simulations.

    ERIC Educational Resources Information Center

    Reinecker, Lynn

    1985-01-01

    Describes technique involved in designing a clinical simulation problem for the allied health field of respiratory therapy; discusses the structure, content, and scoring categories of the simulation; and provides a sample program which illustrates a programming technique in BASIC, including a program listing and a sample flowchart. (MBR)

  16. Designing Clinical Remediation Programs.

    ERIC Educational Resources Information Center

    Oleszewski, Susan C.

    1989-01-01

    Elements and considerations in the provision of effective remediation for optometry students not achieving in clinical competence are discussed. Remediation of technical, cognitive, and noncognitive skills are included. A course in professional communication offered by the Pennsylvania College of Optometry is described. (MSE)

  17. The "Clinical" Masters Degree.

    ERIC Educational Resources Information Center

    Perlman, Baron; Lane, Robert

    1981-01-01

    Discusses issues surrounding the clinical master's degree: the belief that the only true psychologist is a PhD, public confusion between doctoral and subdoctoral psychologists, training guidelines, role responsibility, employment, licensing and competency, accreditation, and supervision. Suggests an APA sponsored conference to discuss and resolve…

  18. Evaluation of Clinical Competence.

    ERIC Educational Resources Information Center

    Newble, David I.

    In Australia the usual evaluation of whether a student will perform adequately as a doctor is a subjective evaluation of his clinical performance, usually at the completion of five or six years at medical school. The evaluation is performed on an inadequate and uncontrolled patient sample and appears to be subject to many errors. Recent work…

  19. Clinical Mastery of Hypnosis.

    ERIC Educational Resources Information Center

    Horevitz, Richard P.

    Hypnosis is an increasingly popular clinical intervention. The number of training courses in hypnosis is growing each year. Research on hypnosis training appears to show that limited exposure to training, as is typical in the common 3 to 5 day format of mass training, produces limited results. Only when training is extended over time do the…

  20. Community Health Clinics, Inc.

    ERIC Educational Resources Information Center

    Reese, David

    1986-01-01

    Describes successful Community Health Clinics, Inc., a private, non-profit health care corporation, founded in 1971, which provides health services for rural and low-income residents of southwestern Idaho. Focuses on administrative structure, staff, financial support, and services. (NEC)

  1. The Unstructured Clinical Interview

    ERIC Educational Resources Information Center

    Jones, Karyn Dayle

    2010-01-01

    In mental health, family, and community counseling settings, master's-level counselors engage in unstructured clinical interviewing to develop diagnoses based on the "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.; "DSM-IV-TR"; American Psychiatric Association, 2000). Although counselors receive education about…

  2. Clinical protein mass spectrometry.

    PubMed

    Scherl, Alexander

    2015-06-15

    Quantitative protein analysis is routinely performed in clinical chemistry laboratories for diagnosis, therapeutic monitoring, and prognosis. Today, protein assays are mostly performed either with non-specific detection methods or immunoassays. Mass spectrometry (MS) is a very specific analytical method potentially very well suited for clinical laboratories. Its unique advantage relies in the high specificity of the detection. Any protein sequence variant, the presence of a post-translational modification or degradation will differ in mass and structure, and these differences will appear in the mass spectrum of the protein. On the other hand, protein MS is a relatively young technique, demanding specialized personnel and expensive instrumentation. Many scientists and opinion leaders predict MS to replace immunoassays for routine protein analysis, but there are only few protein MS applications routinely used in clinical chemistry laboratories today. The present review consists of a didactical introduction summarizing the pros and cons of MS assays compared to immunoassays, the different instrumentations, and various MS protein assays that have been proposed and/or are used in clinical laboratories. An important distinction is made between full length protein analysis (top-down method) and peptide analysis after enzymatic digestion of the proteins (bottom-up method) and its implication for the protein assay. The document ends with an outlook on what type of analyses could be used in the future, and for what type of applications MS has a clear advantage compared to immunoassays.

  3. Clinical immunoassay instrument markets

    SciTech Connect

    Not Available

    1984-11-01

    The present status and future prospects of the market for clinical immunoassay instruments is discussed. The market shares for the five basic instrument types - nephelometric immunoassay, fluorescence immmunoassay, enzyme immunoassay, luminescence immunoassay, and radioimmunoassay are presented. It is noted that radioimmunoassay hold a major, but decreasing, share of the market.

  4. Evaluating Student Clinical Performance.

    ERIC Educational Resources Information Center

    Foster, Danny T.

    When the University of Iowa's athletic training education department developed evaluation criteria and methods to be used with students, attention was paid to validity, consistency, observation, and behaviors. The observations of student behaviors reflect three types of learning outcomes important to clinical education: cognitive, psychomotor, and…

  5. Clinical Management of Cluttering.

    ERIC Educational Resources Information Center

    St. Louis, Kenneth O.; Myers, Florence L.

    1995-01-01

    This article proposes a synergistic, interactive model of cluttering, a fluency disorder manifested in rapid or erratic speech rates, reduced intelligibility, and language deviations. Clinical strategies are presented in a framework of several working assumptions about cluttering. Despite encouraging reports, further research into the nature and…

  6. Clinical Intuition at Play

    ERIC Educational Resources Information Center

    Marks-Tarlow, Terry

    2014-01-01

    A clinical psychologist and consulting psychotherapist discusses how elements of play, inherent in the intuition required in analysis, can provide a cornerstone for serious therapeutic work. She argues that many aspects of play--its key roles in human development, individual growth, and personal creativity, among others--can help therapists and…

  7. [Management in clinical nutrition].

    PubMed

    Alvarez, J; Monereo, S; Ortiz, P; Salido, C

    2004-01-01

    Terms such as management, costs, efficacy, efficiency, etc. that are so common in the discourse of managers are now beginning to appear in the vocabulary of clinicians. Management in Clinical Nutrition is an innovative aspect of interest among health-care professionals dealing with the needs of undernourished patients or those at risk of malnutrition. The basic goal of this paper is to show that the tools for clinical management of hospitals are applicable to such a multidisciplinary and complex speciality as clinical nutrition and also to propose the measures needed to improve our information systems and optimize management in this field. The very concept of hospitals has changed, as has their activity, over the years. Hospitals are nowadays no longer just a charitable institution but has become a service company, a public utility for the promotion of good health and they have to be managed in accordance with criteria of efficacy, efficiency, equity and quality. The concepts of Evidence-Based Medicine (EBM) and Cost-Effective Medicine (CEM) are of evident importance in the different ways of managing health-care services. Good clinical practice is the combination of EBM and CEM. This review defines the various cost studies of fundamental importance when taking decisions in hospital management and analyzes such clinical management tools as analytical accounting, Minimum Hospital Database Set (MHDS) and encoding systems, among others, thus facilitating an analysis of the usefulness of data in clinical nutrition management systems. Finally, after reviewing some specific examples, measures are proposed to optimize current information systems. The medical staff and those of us responsible for Nutrition Units operate in hospitals as part of a centralized service transferring information to the various departments where the patient is physically located (Surgery, Internal Medicine, Digestive, ICU, etc.). One of the priority goals in micro-management and middle management

  8. Integrated clinical information system.

    PubMed

    Brousseau, G

    1995-01-01

    SIDOCI (Système Informatisé de DOnnées Cliniques Intégrées) is a Canadian joint venture introducing newly-operating paradigms into hospitals. The main goal of SIDOCI is to maintain the quality of care in todayUs tightening economy. SIDOCI is a fully integrated paperless patient-care system which automates and links all information about a patient. Data is available on-line and instantaneously to doctors, nurses, and support staff in the format that best suits their specific requirements. SIDOCI provides a factual and chronological summary of the patient's progress by drawing together clinical information provided by all professionals working with the patient, regardless of their discipline, level of experience, or physical location. It also allows for direct entry of the patient's information at the bedside. Laboratory results, progress notes, patient history and graphs are available instantaneously on screen, eliminating the need for physical file transfers. The system, incorporating a sophisticated clinical information database, an intuitive graphical user interface, and customized screens for each medical discipline, guides the user through standard procedures. Unlike most information systems created for the health care industry, SIDOCI is longitudinal, covering all aspects of the health care process through its link to various vertical systems already in place. A multidisciplinary team has created a clinical dictionary that provides the user with most of the information she would normally use: symptoms, signs, diagnoses, allergies, medications, interventions, etc. This information is structured and displayed in such a manner that health care professionals can document the clinical situation at the touch of a finger. The data is then encoded into the patient's file. Once encoded, the structured data is accessible for research, statistics, education, and quality assurance. This dictionary complies with national and international nomenclatures. It also

  9. Integrated clinical information system.

    PubMed

    Brousseau, G

    1995-01-01

    SIDOCI (Système Informatisé de DOnnées Cliniques Intégrées) is a Canadian joint venture introducing newly-operating paradigms into hospitals. The main goal of SIDOCI is to maintain the quality of care in todayUs tightening economy. SIDOCI is a fully integrated paperless patient-care system which automates and links all information about a patient. Data is available on-line and instantaneously to doctors, nurses, and support staff in the format that best suits their specific requirements. SIDOCI provides a factual and chronological summary of the patient's progress by drawing together clinical information provided by all professionals working with the patient, regardless of their discipline, level of experience, or physical location. It also allows for direct entry of the patient's information at the bedside. Laboratory results, progress notes, patient history and graphs are available instantaneously on screen, eliminating the need for physical file transfers. The system, incorporating a sophisticated clinical information database, an intuitive graphical user interface, and customized screens for each medical discipline, guides the user through standard procedures. Unlike most information systems created for the health care industry, SIDOCI is longitudinal, covering all aspects of the health care process through its link to various vertical systems already in place. A multidisciplinary team has created a clinical dictionary that provides the user with most of the information she would normally use: symptoms, signs, diagnoses, allergies, medications, interventions, etc. This information is structured and displayed in such a manner that health care professionals can document the clinical situation at the touch of a finger. The data is then encoded into the patient's file. Once encoded, the structured data is accessible for research, statistics, education, and quality assurance. This dictionary complies with national and international nomenclatures. It also

  10. Clinical governance. Scope to improve.

    PubMed

    Walshe, K; Freeman, T; Latham, L; Spurgeon, P; Wallace, L

    2000-10-26

    A survey of all 47 trusts in the West Midlands found that clinical governance had not been advanced beyond the production of strategies, establishing committees and appointing leads. There is little evidence of the cultural change clinical governance requires. Clinical governance has yet to make a real difference at the clinical workface. PMID:11138206

  11. Clinical Genomic Database

    PubMed Central

    Solomon, Benjamin D.; Nguyen, Anh-Dao; Bear, Kelly A.; Wolfsberg, Tyra G.

    2013-01-01

    Technological advances have greatly increased the availability of human genomic sequencing. However, the capacity to analyze genomic data in a clinically meaningful way lags behind the ability to generate such data. To help address this obstacle, we reviewed all conditions with genetic causes and constructed the Clinical Genomic Database (CGD) (http://research.nhgri.nih.gov/CGD/), a searchable, freely Web-accessible database of conditions based on the clinical utility of genetic diagnosis and the availability of specific medical interventions. The CGD currently includes a total of 2,616 genes organized clinically by affected organ systems and interventions (including preventive measures, disease surveillance, and medical or surgical interventions) that could be reasonably warranted by the identification of pathogenic mutations. To aid independent analysis and optimize new data incorporation, the CGD also includes all genetic conditions for which genetic knowledge may affect the selection of supportive care, informed medical decision-making, prognostic considerations, reproductive decisions, and allow avoidance of unnecessary testing, but for which specific interventions are not otherwise currently available. For each entry, the CGD includes the gene symbol, conditions, allelic conditions, clinical categorization (for both manifestations and interventions), mode of inheritance, affected age group, description of interventions/rationale, links to other complementary databases, including databases of variants and presumed pathogenic mutations, and links to PubMed references (>20,000). The CGD will be regularly maintained and updated to keep pace with scientific discovery. Further content-based expert opinions are actively solicited. Eventually, the CGD may assist the rapid curation of individual genomes as part of active medical care. PMID:23696674

  12. Computers and clinical arrhythmias.

    PubMed

    Knoebel, S B; Lovelace, D E

    1983-02-01

    Cardiac arrhythmias are ubiquitous in normal and abnormal hearts. These disorders may be life-threatening or benign, symptomatic or unrecognized. Arrhythmias may be the precursor of sudden death, a cause or effect of cardiac failure, a clinical reflection of acute or chronic disorders, or a manifestation of extracardiac conditions. Progress is being made toward unraveling the diagnostic and therapeutic problems involved in arrhythmogenesis. Many of the advances would not be possible, however, without the availability of computer technology. To preserve the proper balance and purposeful progression of computer usage, engineers and physicians have been exhorted not to work independently in this field. Both should learn some of the other's trade. The two disciplines need to come together to solve important problems with computers in cardiology. The intent of this article was to acquaint the practicing cardiologist with some of the extant and envisioned computer applications and some of the problems with both. We conclude that computer-based database management systems are necessary for sorting out the clinical factors of relevance for arrhythmogenesis, but computer database management systems are beset with problems that will require sophisticated solutions. The technology for detecting arrhythmias on routine electrocardiograms is quite good but human over-reading is still required, and the rationale for computer application in this setting is questionable. Systems for qualitative, continuous monitoring and review of extended time ECG recordings are adequate with proper noise rejection algorithms and editing capabilities. The systems are limited presently for clinical application to the recognition of ectopic rhythms and significant pauses. Attention should now be turned to the clinical goals for detection and quantification of arrhythmias. We should be asking the following questions: How quantitative do systems need to be? Are computers required for the detection of

  13. [Clinical consequences of sarcopenia].

    PubMed

    Serra Rexach, J A

    2006-05-01

    The concept of sarcopenia implies loss of muscle mass and function. It is a condition that accompanies aging, although it not always has clinical consequences. It is produced by many factors: nervous system (loss of alpha motor units in the spinal cord), muscular (loss of muscle quality and mass), humoral (decrease in anabolic hormones such as testosterone, estrogens, GH, and increase of several interleukines), and life style (physical activity). The main clinical consequences of sarcopenia relate with functional independence. Thus, the sarcopenic elderly has greater difficulty walking, or do it more slowly, climbing up stairs, or doing basic daily living activities. These difficulties increase the risk for falls and, thus, fractures. They also affect bone formation, glucose tolerance, and body temperature regulation. Besides, dependency is a mortality risk factor.

  14. Voriconazole in clinical practice.

    PubMed

    Mikulska, Małgorzata; Novelli, Andrea; Aversa, Franco; Cesaro, Simone; de Rosa, Francesco Giuseppe; Girmenia, Corrado; Micozzi, Alessandra; Sanguinetti, Maurizio; Viscoli, Claudio

    2012-12-01

    Invasive fungal diseases are associated with significant morbidity and mortality in immunocompromized patients. Voriconazole is the first line treatment of invasive aspergillosis, and has been successfully used in other invasive fungal infections, such as candidiasis, fusariosis or scedosporidiosis. Voriconazole has non-linear pharmacokinetics and undergoes extensive hepatic metabolism by the cytochrome P450 system that depends on age, genetic factors, and interactions with other drugs. Thus, significant interpatient variability is observed after administration of the same dose. Additionally, the therapeutic window is narrow, with high risk of side effects at serum levels 3-5 times higher than the minimal threshold for efficacy. Therefore, the knowledge of pharmacological properties, metabolism, interactions, dosage indications in various populations and side effects is crucial. Therapeutic drug monitoring can help maximize the efficacy and minimize the risk of toxicity. Pharmacological, mycological and clinical aspects of the treatment with voriconazole are summarized in order to optimize its use in daily clinical practice. PMID:23174096

  15. Clinical trials in children

    PubMed Central

    Joseph, Pathma D; Craig, Jonathan C; Caldwell, Patrina HY

    2015-01-01

    Safety and efficacy data on many medicines used in children are surprisingly scarce. As a result children are sometimes given ineffective medicines or medicines with unknown harmful side effects. Better and more relevant clinical trials in children are needed to increase our knowledge of the effects of medicines and to prevent the delayed or non-use of beneficial therapies. Clinical trials provide reliable evidence of treatment effects by rigorous controlled testing of interventions on human subjects. Paediatric trials are more challenging to conduct than trials in adults because of the paucity of funding, uniqueness of children and particular ethical concerns. Although current regulations and initiatives are improving the scope, quantity and quality of trials in children, there are still deficiencies that need to be addressed to accelerate radically equitable access to evidence-based therapies in children. PMID:24325152

  16. Clinical vaccine development

    PubMed Central

    2015-01-01

    Vaccination is regarded as one of the biggest triumphs in the history of medicine. We are living in the most successful period of vaccine development. The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors. The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical experience. However, there remain a number of hurdles to overcome. Continuous efforts are focused on increasing the efficacy and reducing the risks related to vaccine use. Cutting-edge knowledge about immunology and microbiology is being rapidly translated to vaccine development. Thus, physicians and others involved in the clinical development of vaccines should have sufficient understanding of the recent developmental trends in vaccination and the diseases of interest. PMID:25648742

  17. [Clinical diagnosis of dyslexia].

    PubMed

    Martínez Hermosillo, A; Balderas Gil, A

    1980-01-01

    In 5 years of experience at the Instituto Nacional de la Comunicacion Humana, 302 clinical histories showed the diagnosis of dyslexia. The following parameters were studied: age, sex, heredofamilial history, gestation, psychomotor development, clinical picture, examination of the language (type, reading, spontaneous writing, dictation, mathematic concepts), laterality, scholarship, scholar failures, psychological study. The following results were obtained: Dyslexia was more important or frequent between 5 to 8.9 years of age. Males predominated 3:1. The heredofamilial history was important. Dyslexia prevailed in products of the first gestations. A high disturbance was found in the psychomotor development of a large percent of dyslexic patients. Examination of language was also important. Dyslexia was more frequent in right-handed patients. Scholar failures in one or more instances were found. The psychological study must be done. If dyslexia is diagnosed on time, it may be prevented and all unwanted sequelae may be avoided.

  18. Clinical applications for estetrol.

    PubMed

    Visser, Monique; Coelingh Bennink, Herjan J T

    2009-03-01

    In this paper the potential clinical applications for the human fetal estrogen estetrol (E(4)) are presented based on recently obtained data in preclinical and clinical studies. In the past E(4) has been classified as a weak estrogen due to its rather low estrogen receptor affinity. However, recent research has demonstrated that due to its favorable pharmacokinetic properties, especially the slow elimination and long half-life, E(4) is an effective orally bioavailable estrogen agonist with estrogen antagonistic effects on the breast in the presence of estradiol. Based on the pharmacokinetic properties, the pharmacological profile and the safety and efficacy results in human studies, E(4) seems potentially suitable as a drug for human use in applications such as hormone replacement therapy (vaginal atrophy and vasomotor symptoms), contraception, osteoporosis and breast cancer. PMID:19167495

  19. Models for transition clinics.

    PubMed

    Carrizosa, Jaime; An, Isabelle; Appleton, Richard; Camfield, Peter; Von Moers, Arpad

    2014-08-01

    Transition is a purposeful, planned process that addresses the medical, psychosocial, educational, and vocational needs of adolescents and young adults with chronic medical conditions, as they advance from a pediatric and family-centered to an adult, individual focused health care provider. This article describes some of the models for transition clinics or services for epilepsy in five countries (Canada, France, Colombia, Germany, and the United Kingdom). These models include joint adult and pediatric clinics, algorithm-driven service, and a check list system in the context of pediatric care. Evaluation of these models is limited, and it is not possible to choose an optimal program. The attitude and motivation of health care providers may be the most important elements. PMID:25209087

  20. Clinical features of actinomycosis

    PubMed Central

    Bonnefond, Simon; Catroux, Mélanie; Melenotte, Cléa; Karkowski, Ludovic; Rolland, Ludivine; Trouillier, Sébastien; Raffray, Loic

    2016-01-01

    Abstract Actinomycosis is a rare heterogeneous anaerobic infection with misleading clinical presentations that delay diagnosis. A significant number of misdiagnosed cases have been reported in specific localizations, but studies including various forms of actinomycosis have rarely been published. We performed a multicenter retrospective chart review of laboratory-confirmed actinomycosis cases from January 2000 until January 2014. We described clinical characteristics, diagnostic procedures, differential diagnosis, and management of actinomycosis of clinical significance. Twenty-eight patients were included from 6 hospitals in France. Disease was diagnosed predominately in the abdomen/pelvis (n = 9), orocervicofacial (n = 5), cardiothoracic (n = 5), skeletal (n = 3), hematogenous (n = 3), soft tissue (n = 2), and intracranially (n = 1). Four patients (14%) were immunocompromised. In most cases (92 %), the diagnosis of actinomycosis was not suspected on admission, as clinical features were not specific. Diagnosis was obtained from either microbiology (50%, n = 14) or histopathology (42%, n = 12), or from both methods (7%, n = 2). Surgical biopsy was needed for definite diagnosis in 71% of cases (n = 20). Coinfection was found in 13 patients (46%), among which 3 patients were diagnosed from histologic criteria only. Two-thirds of patients were treated with amoxicillin. Median duration of antibiotics was 120 days (interquartile range 60–180), whereas the median follow-up time was 12 months (interquartile range 5.25–18). Two patients died. This study highlights the distinct and miscellaneous patterns of actinomycosis to prompt accurate diagnosis and earlier treatments, thus improving the outcome. Surgical biopsy should be performed when possible while raising histologist's and microbiologist's awareness of possible actinomycosis to enhance the chance of diagnosis and use specific molecular methods. PMID:27311002

  1. Pharmacovigilance using Clinical Text

    PubMed Central

    LePendu, Paea; Iyer, Srinivasan V; Bauer-Mehren, Anna; Harpaz, Rave; Ghebremariam, Yohannes T; Cooke, John P; Shah, Nigam H

    2013-01-01

    The current state of the art in post-marketing drug surveillance utilizes voluntarily submitted reports of suspected adverse drug reactions. We present data mining methods that transform unstructured patient notes taken by doctors, nurses and other clinicians into a de-identified, temporally ordered, patient-feature matrix using standardized medical terminologies. We demonstrate how to use the resulting high-throughput data to monitor for adverse drug events based on the clinical notes in the EHR. PMID:24303315

  2. Dismissal for clinical deficiencies.

    PubMed

    Parrott, T E

    1993-01-01

    Students may challenge decisions of academic dismissal through local grievance procedures and the court system. When public safety and security are at issue, however, nursing faculty have the responsibility of dismissing students based on clinical performance. When due process is adequately served and students' civil rights protected, the courts have repeatedly upheld decisions made by higher education faculty and grievance committees. The author discusses several precedent-setting cases.

  3. Clinical highlights from Amsterdam

    PubMed Central

    Vogiatzis, Ioannis; Grgic, Aleksander; Antoniou, Katerina; Ställberg, Björn; Herth, Felix F.

    2016-01-01

    This article contains highlights and a selection of the scientific advances from the Clinical Assembly that were presented at the 2015 European Respiratory Society International Congress in Amsterdam, the Netherlands. The most relevant topics for clinicians will be discussed, covering a wide range of areas including interventional pulmonology, rehabilitation and chronic care, thoracic imaging, diffuse and parenchymal lung diseases, and general practice and primary care. In this comprehensive review, exciting novel data will be discussed and put into perspective. PMID:27730202

  4. Rural health clinics infrastructure

    SciTech Connect

    Olson, K.

    1997-12-01

    The author discusses programs which were directed at the installation of photovoltaic power systems in rural health clinics. The objectives included: vaccine refrigeration; ice pack freezing; lighting; communications; medical appliances; sterilization; water purification; and income generation. The paper discusses two case histories, one in the Dominican Republic and one in Colombia. The author summarizes the results of the programs, both successes and failures, and offers an array of conclusions with regard to the implementation of future programs of this general nature.

  5. [Electronic glottography (clinical aspects)].

    PubMed

    Chernobel'skiĭ, S I

    1991-01-01

    In order to study the application of electronic glottography in clinical laryngology, 200 patients with different diseases were examined, using a glottographic unit, computer, oscilloscope, and a recorder. It was found that glottography is an objective method which can be applied to evaluate and detect disorders of vocal folds in different states. This method fails to determine the vibration capacity of an individual fold or diagnose laryngeal lesions without an additional examination.

  6. Clinical multiphoton FLIM tomography

    NASA Astrophysics Data System (ADS)

    König, Karsten

    2012-03-01

    This paper gives an overview on current clinical high resolution multiphoton fluorescence lifetime imaging in volunteers and patients. Fluorescence lifetime imaging (FLIM) in Life Sciences was introduced in Jena/Germany in 1988/89 based on a ZEISS confocal picosecond dye laser scanning microscope equipped with a single photon counting unit. The porphyrin distribution in living cells and living tumor-bearing mice was studied with high spatial, temporal, and spectral resolution. Ten years later, time-gated cameras were employed to detect dental caries in volunteers based on one-photon excitation of autofluorescent bacteria with long fluorescence lifetimes. Nowadays, one-photon FLIM based on picosecond VIS laser diodes are used to study ocular diseases in humans. Already one decade ago, first clinical twophoton FLIM images in humans were taken with the certified clinical multiphoton femtosecond laser tomograph DermaInspectTM. Multiphoton tomographs with FLIM modules are now operating in hospitals at Brisbane, Tokyo, Berlin, Paris, London, Modena and other European cities. Multiple FLIM detectors allow spectral FLIM with a temporal resolution down to 20 ps (MCP) / 250 ps (PMT) and a spectral resolution of 10 nm. Major FLIM applications include the detection of intradermal sunscreen and tattoo nanoparticles, the detection of different melanin types, the early diagnosis of dermatitis and malignant melanoma, as well as the measurement of therapeutic effects in pateints suffering from dermatitis. So far, more than 1,000 patients and volunteers have been investigated with the clinical multiphoton FLIM tomographs DermaInspectTM and MPTflexTM.

  7. Innovative Clinical Trial Designs

    PubMed Central

    Lavori, Philip W.

    2015-01-01

    Whereas the 20th-century health care system sometimes seemed to be inhospitable to and unmoved by experimental research, its inefficiency and unaffordability have led to reforms that foreshadow a new health care system. We point out certain opportunities and transformational needs for innovations in study design offered by the 21st-century health care system, and describe some innovative clinical trial designs and novel design methods to address these needs and challenges. PMID:26140056

  8. Clinically Available Pharmacogenomics Tests

    PubMed Central

    Flockhart, DA; Skaar, T; Berlin, DS; Klein, TE; Nguyen, AT

    2009-01-01

    The development of robust and clinically valuable pharmacogenomic tests has been anticipated to be one of the first tangible results of the Human Genome Project. Despite both obvious and unanticipated obstacles, a number of tests have now become available in various practice settings. Lessons can be learned from examination of these tests, the evidence that has catalyzed their use, their value to prescribers, and their merit as tools for personalizing therapeutics. PMID:19369936

  9. Aspartame: clinical update.

    PubMed

    Potenza, D P; el-Mallakh, R S

    1989-07-01

    Since the introduction of aspartame into the American food supply in 1981, it has grown to become the most widely used and accepted artificial sweetener. However, recent published and unpublished reports of headaches, seizures, blindness, and cognitive and behavioral changes with long-term, high-dose aspartame may be cause for concern. Physician awareness of the present clinical and research status of aspartame is important.

  10. [Guidelines for clinical practice].

    PubMed

    Vleugels, A M

    1997-01-01

    Clinical practice guidelines are systematically developed statements that are intended to support medical decision making in well-defined clinical situations. Essentially, their object is to reduce the variability in medical practice, to improve quality, and to make appropriated control of the financial resources possible. Internationally, ever more organisations, associations, and institutions are concerned with the development of guidelines in many different areas of care. Making implicit knowledge explicit is one of the associated advantages of guidelines: they have a potential utility in training, in process evaluation, and in the reevaluation of outcome studies. In liability issues, their existence has a double effect: they can be used to justify medical behaviour, and they constitute a generally accepted reference point. A derivative problem is the legal liability of the compilers of the guidelines. The principle of the guideline approach can be challenged academically: science cannot give a definition of optimal care with absolute certainty. What is called objectivity often rests on methodologically disputable analyses; also the opinion of opinion leaders is not always a guarantee for scientific soundness. Moreover, patients are not all identical: biological variability, situational factors, patient expectations, and other elements play a role in this differentiation. Clinicians are often hesitant with respect to clinical guidelines: they are afraid of cookbook medicine and curtailment of their professional autonomy. Patients fear reduction of individualization of care and the use of guidelines as a rationing instrument. The effects of the introduction of clinical practice guidelines on medical practice, on the results and on the cost of care vary but are generally considered to be favourable. The choice of appropriate strategies in development, dissemination, and implementation turns out to be of critical importance. The article ends with concrete

  11. The IMPACT clinic

    PubMed Central

    Tracy, C. Shawn; Bell, Stephanie H.; Nickell, Leslie A.; Charles, Jocelyn; Upshur, Ross E.G.

    2013-01-01

    Abstract Problem addressed The growing number of elderly patients with multiple chronic conditions presents an urgent challenge in primary care. Current practice models are not well suited to addressing the complex health care needs of this patient population. Objective of program The primary objective of the IMPACT (Interprofessional Model of Practice for Aging and Complex Treatments) clinic was to design and evaluate a new interprofessional model of care for community-dwelling seniors with complex health care needs. A secondary objective was to explore the potential of this new model as an interprofessional training opportunity. Program description The IMPACT clinic is an innovative new model of interprofessional primary care for elderly patients with complex health care needs. The comprehensive team comprises family physicians, a community nurse, a pharmacist, a physiotherapist, an occupational therapist, a dietitian, and a community social worker. The model is designed to accommodate trainees from each discipline. Patient appointments are 1.5 to 2 hours in length, during which time a diverse range of medical, functional, and psychosocial issues are investigated by the full interprofessional team. Conclusion The IMPACT model is congruent with ongoing policy initiatives in primary care reform and enhanced community-based care for seniors. The clinic has been pilot-tested in 1 family practice unit and modeled at 3 other sites with positive feedback from patients and families, clinicians, and trainees. Evaluation data indicate that interprofessional primary care models hold great promise for the growing challenge of managing complex chronic disease. PMID:23486816

  12. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate.

  13. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride.

  14. Standardization in Clinical Enzymology

    PubMed Central

    Infusino, Ilenia; Mauro, Panteghini

    2009-01-01

    The goal of standardization in Laboratory Medicine is to achieve comparable results in human samples, independent of the reagent kits, instruments, and laboratory where the assay is carried out. To pursue this objective in clinical enzymology, the IFCC has established reference measurement systems for the most important clinical enzymes. These systems are based on the following requirements: a) reference methods, well described in procedures that are extensively evaluated; b) suitable reference materials; and c) reference laboratories operating in a highly controlled manner. Using these reference systems and the manufacturer’s standing procedures, industry can assign traceable values to commercial calibrators. Clinical laboratories, which use routine procedures with validated calibrators to measure enzymes in human specimens, can finally obtain values which are traceable to higher-order reference procedures. These reference systems constitute the structure of the traceability chain to which the enzyme routine methods can be linked via an appropriate calibration process, provided that they have a comparable specificity (i.e. they are measuring the same quantity).

  15. Telemedicine in clinical setting

    PubMed Central

    Zhang, Xiao-Ying; Zhang, Peiying

    2016-01-01

    The telemedicine department of a hospital is an emerging branch in upcoming hospitals and may become an essential component of every hospital. It basically utilizes the information technologies along with telecommunication systems in order to provide clinical care and assistance. Furthermore, the branch of telemedicine offers significant opportunities for the process of developmental freedom from illness, early death, and preventable diseases. It advances development by providing relevant drugs and the necessary care aimed to alleviate patient suffering. It is also beneficial for patients in rural remote areas who usually do not have adequate access to advanced hospitals. Telemedicine in these remote areas allows for timely treatment of emergency cases. Thus, it contributes towards remote emergency critical care in order to save lives in crucial cases. Additionally, the emerging advances have now enabled telemedicine to transfer large amounts of clinical informatics data including images, and test reports to the specifically specialized health professionals in some serious cases. However, as in the case of many emerging technologies, organizing information and understanding the field has significant challenges. The present review article aimed to discuss important aspects of the field with regard to the better management of patients in clinical settings. PMID:27703503

  16. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole

  17. Automating clinical dietetics documentation.

    PubMed

    Grace-Farfaglia, P; Rosow, P

    1995-06-01

    A review of commonly used charting formats discussed in the dietetics literature revealed that the subjective, objective assessment and planning (SOAP) approach is most frequently used by dietitians. Formats reported in the nursing literature were charting by exception (CBE); problem, intervention, evaluation (PIE); and focus/data, action, response (Focus/DAR). The strengths and weaknesses of the charting styles as they apply to the needs of clinical dietetic specialists were reviewed. We then decided to test in house the Focus/DAR format by assessing chart entries for adherence to style, brevity, and physician response. Dietitians pilot tested all the methods, but found them time consuming to use. The consensus was that SOAP could be adapted to the documentation needs of the individual situation and required little additional staff training. Often because of time limitations, a narrative summary was most appropriate. Chart entry length was reduced as much as 200% when staff were given brief clinical communication as a goal, and a further reduction when line limits were imposed. The physician response was positive, with recommendations followed in 50% of charts, compared with 34% in a previous audit. A nutrition documentation system was developed by the researchers by reviewing medical chart structure, documentation standards, methods of risk identification, and terminology for clinical documentation style. The resulting system affected the decision making of physicians, who could now scan notes more quickly and implement nutrition recommendations in a more timely fashion.

  18. Basic and clinical immunology

    NASA Technical Reports Server (NTRS)

    Chinen, Javier; Shearer, William T.

    2003-01-01

    Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

  19. Myocarditis in Clinical Practice.

    PubMed

    Sinagra, Gianfranco; Anzini, Marco; Pereira, Naveen L; Bussani, Rossana; Finocchiaro, Gherardo; Bartunek, Jozef; Merlo, Marco

    2016-09-01

    Myocarditis is a polymorphic disease characterized by great variability in clinical presentation and evolution. Patients presenting with severe left ventricular dysfunction and life-threatening arrhythmias represent a demanding challenge for the clinician. Modern techniques of cardiovascular imaging and the exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have provided valuable insight into the pathophysiology of this disease, and several clinical registries have unraveled the disease's long-term evolution and prognosis. However, uncertainties persist in crucial practical issues in the management of patients. This article critically reviews current information for evidence-based management, offering a rational and practical approach to patients with myocarditis. For this review, we searched the PubMed and MEDLINE databases for articles published from January 1, 1980, through December 31, 2015, using the following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial biopsy. Articles were selected for inclusion if they represented primary data or were review articles published in high-impact journals. In particular, a risk-oriented approach is proposed. The different patterns of presentation of myocarditis are classified as low-, intermediate-, and high-risk syndromes according to the most recent evidence on prognosis, clinical findings, and both invasive and noninvasive testing, and appropriate management strategies are proposed for each risk class.

  20. Myocarditis in Clinical Practice.

    PubMed

    Sinagra, Gianfranco; Anzini, Marco; Pereira, Naveen L; Bussani, Rossana; Finocchiaro, Gherardo; Bartunek, Jozef; Merlo, Marco

    2016-09-01

    Myocarditis is a polymorphic disease characterized by great variability in clinical presentation and evolution. Patients presenting with severe left ventricular dysfunction and life-threatening arrhythmias represent a demanding challenge for the clinician. Modern techniques of cardiovascular imaging and the exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have provided valuable insight into the pathophysiology of this disease, and several clinical registries have unraveled the disease's long-term evolution and prognosis. However, uncertainties persist in crucial practical issues in the management of patients. This article critically reviews current information for evidence-based management, offering a rational and practical approach to patients with myocarditis. For this review, we searched the PubMed and MEDLINE databases for articles published from January 1, 1980, through December 31, 2015, using the following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial biopsy. Articles were selected for inclusion if they represented primary data or were review articles published in high-impact journals. In particular, a risk-oriented approach is proposed. The different patterns of presentation of myocarditis are classified as low-, intermediate-, and high-risk syndromes according to the most recent evidence on prognosis, clinical findings, and both invasive and noninvasive testing, and appropriate management strategies are proposed for each risk class. PMID:27489051

  1. Reuse of Clinical Data

    PubMed Central

    2014-01-01

    Summary Objectives To provide an overview of the benefits of clinical data collected as a by-product of the care process, the potential problems with large aggregations of these data, the policy frameworks that have been formulated, and the major challenges in the coming years. Methods This report summarizes some of the major observations from AMIA and IMIA conferences held on this admittedly broad topic from 2006 through 2013. This report also includes many unsupported opinions of the author. Results The benefits of aggregating larger and larger sets of routinely collected clinical data are well documented and of great societal benefit. These large data sets will probably never answer all possible clinical questions for methodological reasons. Non-traditional sources of health data that are patient-sources will pose new data science challenges. Conclusions If we ever hope to have tools that can rapidly provide evidence for daily practice of medicine we need a science of health data perhaps modeled after the science of astronomy. PMID:25123722

  2. The virtual clinical campus.

    PubMed

    Friedman, C P

    1996-06-01

    The increased use of community sites for the clinical training of medical students creates many challenges for educators. Among them is the need to provide students in community settings with access to the same range of educational resources-the medical literature, student colleagues, feedback, and faculty-that are customarily available at academic medical centers. One way to make this access possible is to use information technology to create a "virtual clinical campus," which would allow students to enjoy the best of both worlds: the immersion in primary care offered by the community-based setting and the knowledge-rich resources of the academic medical center, including the all-important library. With a virtual campus in place, students would be able to access most library resources, interact with their peers, ensure that they were meeting the goals of their community rotations, and participate with their colleagues in didactic sessions without having to travel. The virtual campus is technologically feasible and economically within reach. It is possible that the movement of clinical training into the community will make it imperative for all medical students to own their own computers and for medical centers to provide the infrastructure that would enable community sites to have access to a range of educational resources.

  3. Ciliocytophthoria in clinical virology.

    PubMed

    Hadziyannis, E; Yen-Lieberman, B; Hall, G; Procop, G W

    2000-08-01

    Direct immunofluorescence assays (DFAs) are used in the clinical virology laboratory for the rapid detection of viruses. An assessment of the cellularity of specimens submitted for DFA is necessary for the most effective use of this assay. This assessment ensures that an adequate number of the appropriate cells are present for examination. During this assessment, clinical virologists may encounter unfamiliar cellular elements or cellular fragments. One of these elements, ciliocytophthoria, has been misinterpreted as a parasite in specimens submitted for cytologic testing. We describe a similar case in which a technologist thought that ciliocytophthoria possibly represented a ciliated parasite in a nasopharyngeal specimen sent for respiratory syncytial virus DFA. After a thorough morphologic examination, the staff dismissed the possibility of a ciliated parasite. We confirmed this entity as ciliocytophthoria using morphologic criteria and the Diff-Quik stain. This near misidentification of ciliocytophthoria as a ciliated parasite affords us the opportunity to raise the awareness of clinical virologists about ciliocytophthoria. Additionally, we briefly review useful features for differentiating ciliocytophthoria from the only ciliate parasitic for humans, Balantidium coli. Finally, we present the utility of a commonly used cytologic stain, the Diff-Quik stain, for the confirmation of ciliocytophthoria.

  4. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses, which has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, providing information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab; aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride; amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium; cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium; darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium; esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar; fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide; glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium; l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate; methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil; omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide; Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride; Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride; ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin; repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium; tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost; Warfarin sodium; Ximelagatran. PMID:11980386

  5. Ciliocytophthoria in clinical virology.

    PubMed

    Hadziyannis, E; Yen-Lieberman, B; Hall, G; Procop, G W

    2000-08-01

    Direct immunofluorescence assays (DFAs) are used in the clinical virology laboratory for the rapid detection of viruses. An assessment of the cellularity of specimens submitted for DFA is necessary for the most effective use of this assay. This assessment ensures that an adequate number of the appropriate cells are present for examination. During this assessment, clinical virologists may encounter unfamiliar cellular elements or cellular fragments. One of these elements, ciliocytophthoria, has been misinterpreted as a parasite in specimens submitted for cytologic testing. We describe a similar case in which a technologist thought that ciliocytophthoria possibly represented a ciliated parasite in a nasopharyngeal specimen sent for respiratory syncytial virus DFA. After a thorough morphologic examination, the staff dismissed the possibility of a ciliated parasite. We confirmed this entity as ciliocytophthoria using morphologic criteria and the Diff-Quik stain. This near misidentification of ciliocytophthoria as a ciliated parasite affords us the opportunity to raise the awareness of clinical virologists about ciliocytophthoria. Additionally, we briefly review useful features for differentiating ciliocytophthoria from the only ciliate parasitic for humans, Balantidium coli. Finally, we present the utility of a commonly used cytologic stain, the Diff-Quik stain, for the confirmation of ciliocytophthoria. PMID:10923088

  6. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-04-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, adalimumab, alefacept, alemtuzumab, AMG-531, anakinra, armodafinil, asenapine maleate, atazanavir sulfate, atorvastatin; Bortezomib, bosentan; CEB-1555, cetuximab, ciclesonide, clodronate, CT-011; Darifenacin hydrobromide, desloratadine; E-7010, ecallantide, eculizumab, efalizumab, eltrombopag, erlotinib hydrochloride, eslicarbazepine acetate, eszopiclone, ezetimibe; Febuxostat, fosamprenavir calcium, fulvestrant; Gefitinib, genistein; Haemophilus influenzae B vaccine, human papillomavirus vaccine; Imatinib mesylate, insulin glargine; Lenalidomide, liposomal cisplatin; MAb G250, mapatumumab, midostaurin, MP4, mycophenolic acid sodium salt; Natalizumab, neridronic acid, NSC-330507; Oblimersen sodium, ofatumumab, omalizumab, oral insulin, oregovomab; Paliperidone, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pegylated arginine deiminase 20000, pemetrexed disodium, pimecrolimus, pitavastatin, pneumococcal 7-valent conjugate vaccine, prasterone, pregabalin, pumosetrag hydrochloride; Recombinant malaria vaccine, retigabine, rivaroxaban, Ro-26-9228, romidepsin, rosuvastatin calcium, rotavirus vaccine; SGN-30, sitaxsentan sodium, solifenacin succinate, sorafenib, sunitinib malate; Tadalafil, tegaserod maleate, temsirolimus, TER-199, tifacogin, tiludronic acid, tiotropium bromide; Vildagliptin, VNP-40101M, vorinostat; YM-150, yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zoledronic acid monohydrate. PMID:16810345

  7. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib

  8. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-04-01

    Gateways to clinical trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5A8; Agomelatine, alefacept, almotriptan, anakinra, APC-8015, atazanavir, atomoxetine hydrochloride, azimilide hydrochloride; Bicifadine; Cannabidiol, caspofungin acetate, CAT-213, CGP-51901, ciclesonide, cipamfylline; Darbepoetin alfa, desloratadine, dibotermin alfa, DX-9065a; Ecogramostim, efalizumab, eletriptan, eniluracil, EPI-KAL2, erlosamide, ertapenem sodium, etilevodopa, etoricoxib, ezetimibe; Fosamprenavir calcium, fosamprenavir sodium, fumagillin; Gadofosveset sodium, gefitinib, gemtuzumab ozogamicin; HSPPC-96, human papillomavirus vaccine; Icatibant Id-KLH, imatinib mesylate, INS-37217, iodine (I131) tositumomab; LAS-34475, levobupivacaine hydrochloride, levocetirizine, linezolid, 131I-lipiodol, lonafarnib, lopinavir, LY-450108; Magnetites, MBI-594AN, melagatran, melatonin, mepolizumab, mycophenolic acid sodium salt; NC-100100; 1-Octanol, omalizumab, omapatrilat, onercept; PEG-filgrastim, (PE)HRG21, peginterferon alfa-2a, peginterferon alfa-2b, pleconaril, pneumococcal 7-valent conjugate vaccine, prasterone; Ranelic acid distrontium salt, rasagiline mesilate, reslizumab, rFGF-2, rhOP-1, rosuvastatin calcium, roxifiban acetate; Sitaxsentan sodium, sodium lauryl sulfate; Tadalafil, telithromycin, tenofovir disoproxil fumarate, tipranavir, TMC-114, tucaresol; Valdecoxib, voriconazole; Ximelagatran; Zofenopril calcium, zosuquidar trihydrochloride. PMID:12743628

  9. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, 667-coumate, 9-aminocamptothecin; Ad5CMV-p53, AES-14, alefacept, anecortave acetate, APC-8024, APD-356, asoprisnil; Bevacizumab, bimakalim, bimatoprost, BLP-25, BR-1; Caspofungin acetate, cetuximab, cypher; Darbepoetin alfa, dexanabinol, dextromethorphan/quinidine sulfate, DNA.HIVA; Efaproxiral sodium, ertapenem sodium; Frovatriptan; HuMax-EGFr, HYB-2055, gamma-hydroxybutyrate sodium, Id-KLH vaccine, imatinib mesylate; Lapatinib, lonafarnib, Motexafin lutetium, MVA.HIVA, mycophenolic acid sodium salt; Nesiritide, NS-2330; Olmesartan medoxomil; Peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, perifosine, pimecrolimus, pregabalin; QbG-10; Ralfinamide, rasburicase, rFGF-2, Ro-31-7453; Sitaxsentan sodium, sorafenib; Tadalafil, TC-1734, telmisartan/hydrochlorothiazide, tenofovir disoproxil fumarate, thymus nuclear protein, tipifarnib; Vandetanib, vibriolysin, vildagliptin, voriconazole. PMID:15834466

  10. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-06-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-chlorotoxin; Ad5CMV-p53, adalimumab, albumin interferon alfa, alemtuzumab, aliskiren fumarate, aminolevulinic acid methyl ester, anakinra, AR-C126532, atomoxetine hydrochloride; Bevacizumab, bosentan, botulinum toxin type B, brimonidine tartrate/timolol maleate; Calcipotriol/betamethasone dipropionate, cangrelor tetrasodium, cetuximab, ciclesonide, cinacalcet hydrochloride, collagen-PVP, Cypher; Darbepoetin alfa, darusentan, dasatinib, denosumab, desloratadine, dexosome vaccine (lung cancer), dexrazoxane, dextromethorphan/quinidine sulfate, duloxetine hydrochloride; ED-71, eel calcitonin, efalizumab, entecavir, etoricoxib; Falciparum merozoite protein-1/AS02A, fenretinide, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gefitinib, ghrelin (human); hLM609; Icatibant acetate, imatinib mesylate, ipsapirone, irofulven; LBH-589, LE-AON, levocetirizine, LY-450139; Malaria vaccine, mapatumumab, motexafin gadolinium, muraglitazar, mycophenolic acid sodium salt; nab-paclitaxel, nelarabine; O6-Benzylguanine, olmesartan medoxomil, orbofiban acetate; Panitumumab, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, peptide YY3-36, pleconaril, prasterone, pregabalin; Ranolazine, rebimastat, recombinant malaria vaccine, rosuvastatin calcium; SQN-400; Taxus, tegaserod maleate, tenofovir disoproxil fumarate, teriparatide, troxacitabine; Valganciclovir hydrochloride, Val-Tyr sardine peptidase, VNP-40101M, vorinostat. PMID:16845450

  11. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, ABX-EGF, acetyldinaline, ACIDFORM, acyline, afeletecan hydrochloride, anecortave acetate, apolizumab, l-arginine hydrochloride, asimadoline, atazanavir sufate, atlizumab; BMS-181176, BMS-188667; CAB-175, carnosine, CDP-870, CEP-701, CEP-7055, CGC-1072, ChimeriVax-JE, ciclesonide, cilomilast, clofarabine, combretastatin A-4 phosphate, cryptophycin 52; Duloxetine hydrochloride; E-5564, eculizumab, elcometrine, emtricitabine, ENO, epratuzumab, eszopiclone, everolimus; Fampridine, flurbiprofen nitroxybutyl ester; Garenoxacin mesilate, gestodene, GI-181771, gimatecan, gomiliximab; Halofuginone hydrobromide, hGH, hLM609; ICA-17043, IL-1 receptor type II, IMC-1C11, iodine (I131) tositumomab, irofulven, ISAtx-247; J591; L-778123, lanthanum carbonate Lasofoxifene tartrate, LDP-02, LE-AON, leteprinim potassium, lintuzumab, liraglutide, lubiprostone, lumiracoxib, lurtotecan, LY-450108, LY-451395; MAb G250, magnesium sulfate, MDX-210, melatonin, 2-methoxy-estradiol, monophosphoryl lipid A; NM-3, nolpitantium besilate; Ocinaplon, olpadronic acid sodium salt, oral heparin; Palonosetron hydrochloride, pemetrexed disodium, PI-88, picoplatin, plevitrexed, polyphenon E, pramlintide acetate, pregabalin, prinomastat, pyrazoloacridine; Resiniferatoxin, rhEndostatin, roxifiban acetate; S-18886, siplizumab, sitaxsentan sodium, solifenacin succinate, SU-11248, SU-6668; Talampanel, TAPgen, testosterone transdermal gel, trabectedin; VEGF-2 gene therapy, visilizumab; ZD-6416, ZD-6474. PMID:12949633

  12. Gateways to Clinical Trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil

  13. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Aciclovir, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alteplase, amifostine hydrate, antithymocyte globulin (equine), aspirin, atorvastatin calcium, azathioprine; Bacillus Calmette-Guérin, basiliximab, bicalutamide, bimatoprost, BMS-214662, brimonidine tartrate, buprenorphine hydrochloride; Cabergoline, carbamazepine, carboplatin, ciclosporine, cisplatin, cyclophosphamide; Daclizumab, desmopressin acetate, dihydroergotamine mesylate, dorzolamide hydrochloride, doxorubicin, dutasteride; Everolimus; Fluocinolone acetonide, frovatriptan, FTY-720, fulvestrant; Gabapentin, galantamine hydrobromide, ganciclovir, gemcitabine, glatiramer acetate; Hydrocodone bitartrate; Interferon beta, interferon beta-1a, interferon beta-1b, ipratropium bromide; Ketotifen; Lamivudine, latanoprost, levodopa, lidocaine hydrochloride, lonafarnib; Metformin hydrochloride, methylprednisolone, metoclopramide hydrochloride, mirtazapine, mitoxantrone hydrochloride, modafinil, muromonab-CD3, mycophenolate mofetil; NS-2330; Olopatadine hydrochloride, omalizumab, oxcarbazepine, oxycodone hydrochloride; Paclitaxel, paracetamol, piribedil, pramipexole hydrochloride, pravastatin sodium, prednisone; Quetiapine fumarate; Raloxifene hydrochloride, rituximab, rizatriptan sulfate, Ro-63-8695, ropinirole hydrochloride, rosiglitazone maleate; Simvastatin, siplizumab, sirolimus; Tacrolimus, tegaserod maleate, timolol maleate, tiotropium bromide, tipifarnib, tizanidine hydrochloride, tolterodine tartrate, topiramate, travoprost; Unoprostone isopropyl ester; Valganciclovir hydrochloride, visilizumab; Zidovudine. PMID:12224444

  14. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, adalimumab, AERx morphine sulphate, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, almotriptan, amprenavir, aripiprazole, atenolol, atorvastatin calcium; BSYX-A110; Cantuzumab mertansine, capravirine, CDP-571, CDP-870, celecoxib; Delavirdine mesilate, docetaxel, dofetilide, donepezil hydrochloride, duloxetine hydrochloride, dutasteride, dydrogesterone; Efavirenz, emtricitabine, enjuvia, enteryx, epristeride, erlotinib hydrochloride, escitalopram oxalate, etanercept, etonogestrel, etoricoxib; Fesoterodine, finasteride, flt3ligand; Galantamine hydrobromide, gemtuzumab ozogamicin, genistein, gepirone hydrochloride; Indinavir sulfate, infliximab; Lamivudine, lamivudine/zidovudine/abacavir sulfate, leteprinim potassium, levetiracetam, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, losartan potassium; MCC-465, MRA; Nebivolol, nesiritide, nevirapine; Olanzapine, OROS(R)-Methylphenidate hydrochloride; Peginterferon alfa-2a, peginterferon alfa-2b, Pimecrolimus, polyethylene glycol 3350, pramlintide acetate, pregabalin, PRO-2000; Risedronate sodium, risperidone, ritonavir, rituximab, rivastigmine tartrate, rofecoxib, rosuvastatin calcium; Saquinavir mesilate, Stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride, telmisartan, tomoxetine hydrochloride, treprostinil sodium, trimegestone, trimetrexate; Valdecoxib, venlafaxine hydrochloride; Zoledronic acid monohydrate. PMID:12616965

  15. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3,4-DAP; Adefovir dipivoxil, ADL-10-0101, alefacept, alemtuzumab, alosetron hydrochloride, ALT-711, aprepitant, atazanavir sulfate, atlizumab, atvogen; Bortezomib; CETP vaccine, clevudine, crofelemer; DAC:GLP-1, darbepoetin alfa, decitabine, drotrecogin alfa (activated), DX-9065a; E-7010, edodekin alfa, emivirine, emtricitabine, entecavir, erlosamide, erlotinib hydrochloride, everolimus, exenatide; Fondaparinux sodium, frovatriptan, fulvestrant; Gemtuzumab ozogamicin, gestodene; Homoharringtonine, human insulin; Imatinib mesylate, indiplon, indium 111 (111In) ibritumomab tiuxetan, inhaled insulin, insulin detemir, insulin glargine, ivabradine hydrochloride; Lanthanum carbonate, lapatinib, LAS-34475, levetiracetam, liraglutide, lumiracoxib; Maxacalcitol, melagatran, micafungin sodium; Natalizumab, NSC-640488; Oblimersen sodium; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2(a), peginterferon alfa-2b, pexelizumab, pimecrolimus, pleconaril, pramlintide acetate, pregabalin, prucalopride; rAHF-PFM, Ranelic acid distrontium salt, ranolazine, rDNA insulin, recombinant human soluble thrombomodulin, rhGM-CSF, roxifiban acetate, RSD-1235, rubitecan, ruboxistaurin mesilate hydrate; SC-51, squalamine; Tegaserod maleate, telbivudine, tesaglitazar, testosterone gel, tezosentan disodium, tipranavir; Vatalanib succinate; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:14671684

  16. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride. PMID:15672123

  17. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate. PMID:16082427

  18. Dissociation: the clinical realities.

    PubMed

    Frankel, F H

    1996-07-01

    An attempt was made by the authors of DSM-III to restrict its focus to the experimental, the observable, and the measurable. The intention was to free the nosology from the influence of unproven theories, and the philosophy was driven largely by the importance of research being able to identify diagnostic categories to facilitate the study of homogeneous groups. So it is of interest that the authors accepted dissociation-an ambiguous event linked to an explicit theoretical concept that had been introduced by Janet-as the basis for classification of clinical presentations that were formerly included under the rubric of hysteria, a similarly unclear category. Since DSM-III, there have been an increasing number of reports of dissociative experiences and dissociative identity disorder (formerly known as multiple personality disorder), but neither of these clinical presentations seems able to withstand the concern that it is dramatically influenced by environmental cues, e.g., the expectations of the therapist. Thus, a restricted phenomenological perspective does not fully appreciate the distorting potential of suggestibility and imagination on the nature of the emerging clinical picture. These factors might well have contributed to and laid the conceptual groundwork for the growth in the number of reports of dissociation.

  19. Clinical Assay Development Support - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The NCI’s Division of Cancer Treatment and Diagnosis and the Cancer Diagnosis Program announce a request for applications for the Clinical Assay Development Program (CADP) for investigators seeking clinical assay development and validation resources.

  20. A clinical academic practice partnership: a clinical education redesign.

    PubMed

    Jeffries, Pamela R; Rose, Linda; Belcher, Anne E; Dang, Deborah; Hochuli, Jo Fava; Fleischmann, Debbie; Gerson, Linda; Greene, Mary Ann; Jordan, Elizabeth Betty T; Krohn, Vicki L; Sartorius-Merganthaler, Susan; Walrath, Jo M

    2013-01-01

    The clinical academic practice partnership (CAPP), a clinical redesign based on the dedicated education unit concept, was developed and implemented by large, private school of nursing in collaboration with 4 clinical partners to provide quality clinical education, to explore new clinical models for the future, and to test an innovative clinical education design. An executive steering committee consisting of nursing leaders and educators from the school of nursing and the clinical institutions was established as the decision-making and planning components, with several collaborative task forces initiated to conduct the work and to accomplish the goals. This article will describe methods to initiate and to organize the key elements of this dedicated education unit-type clinical model, providing examples and an overview of the steps and elements needed as the development proceeded. After 18 months of implementation in 4 different nursing programs in 4 different clinical institutions, the clinical redesign has shown to be a positive initiative, with students actively requesting CAPP units for their clinical experiences. Preliminary findings and outcomes will be discussed, along with nursing education implications for this new clinical redesign.

  1. "Clinical Reasoning Theater": A New Approach to Clinical Reasoning Education.

    ERIC Educational Resources Information Center

    Borleffs, Jan C. C.; Custers, Eugene J. F. M.; van Gijn, Jan; ten Gate, Olle Th. J.

    2003-01-01

    Describes a new approach to clinical reasoning education called clinical reasoning theater (CRT). With students as the audience, the doctor's clinical reasoning skills are modeled in CRT when he or she thinks aloud during conversations with the patient. Preliminary results of students' evaluations of the relevance of CRT reveal that they…

  2. Development and Clinical Outcomes of a Dialectical Behavior Therapy Clinic

    ERIC Educational Resources Information Center

    Lajoie, Travis; Sonkiss, Joshua; Rich, Anne

    2011-01-01

    Objective: The authors describe the first 6 months of a dialectical behavior therapy (DBT) clinic operated by trainees in a general adult psychiatry residency program. The purpose of this report is to provide a model for the creation and maintenance of a formalized resident DBT clinic. Methods: Residents participated in the DBT clinic, attended a…

  3. Terminal Behavioral Objectives for Teaching Clinical Toxicology to Clinical Pharmacists

    ERIC Educational Resources Information Center

    Veltri, Joseph C.; And Others

    1976-01-01

    As a first step in the development of a competency-based clinical toxicology clerkship, a set of terminal behavioral objectives were developed that reflect the anticipated role that clinical pharmacists should play as part of the clinical toxicology team. The evaluation approaches used at the University of Utah are presented. (LBH)

  4. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  5. Clinical management of SIADH

    PubMed Central

    2012-01-01

    Hyponatremia is the most frequent electrolyte disorder and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) accounts for approximately one-third of all cases. In the diagnosis of SIADH it is important to ascertain the euvolemic state of extracellular fluid volume, both clinically and by laboratory measurements. SIADH should be treated to cure symptoms. While this is undisputed in the presence of grave or advanced symptoms, the clinical role and the indications for treatment in the presence of mild to moderate symptoms are currently unclear. Therapeutic modalities include nonspecific measures and means (fluid restriction, hypertonic saline, urea, demeclocycline), with fluid restriction and hypertonic saline commonly used. Recently vasopressin receptor antagonists, called vaptans, have been introduced as specific and direct therapy of SIADH. Although clinical experience with vaptans is limited at this time, they appear advantageous to patients because there is no need for fluid restriction and the correction of hyponatremia can be achieved comfortably and within a short time. Vaptans also appear to be beneficial for physicians and staff because of their efficiency and reliability. The side effects are thirst, polydipsia and frequency of urination. In any therapy of chronic SIADH it is important to limit the daily increase of serum sodium to less than 8–10 mmol/liter because higher correction rates have been associated with osmotic demyelination. In the case of vaptan treatment, the first 24 h are critical for prevention of an overly rapid correction of hyponatremia and the serum sodium should be measured after 0, 6, 24 and 48 h of treatment. Discontinuation of any vaptan therapy for longer than 5 or 6 days should be monitored to prevent hyponatremic relapse. It may be necessary to taper the vaptan dose or restrict fluid intake or both. PMID:23148195

  6. Philosophy of clinical psychopharmacology.

    PubMed

    Aragona, Massimiliano

    2013-03-01

    The renewal of the philosophical debate in psychiatry is one exciting news of recent years. However, its use in psychopharmacology may be problematic, ranging from self-confinement into the realm of values (which leaves the evidence-based domain unchallenged) to complete rejection of scientific evidence. In this paper philosophy is conceived as a conceptual audit of clinical psychopharmacology. Its function is to criticise the epistemological and methodological problems of current neopositivist, ingenuously realist and evidence-servant psychiatry from within the scientific stance and with the aim of aiding psychopharmacologists in practicing a more self-aware, critical and possibly useful clinical practice. Three examples are discussed to suggest that psychopharmacological practice needs conceptual clarification. At the diagnostic level it is shown that the crisis of the current diagnostic system and the problem of comorbidity strongly influence psychopharmacological results, new conceptualizations more respondent to the psychopharmacological requirements being needed. Heterogeneity of research samples, lack of specificity of psychotropic drugs, difficult generalizability of results, need of a phenomenological study of drug-induced psychopathological changes are discussed herein. At the methodological level the merits and limits of evidence-based practice are considered, arguing that clinicians should know the best available evidence but that guidelines should not be constrictive (due to several methodological biases and rhetorical tricks of which the clinician should be aware, sometimes respondent to extra-scientific, economical requests). At the epistemological level it is shown that the clinical stance is shaped by implicit philosophical beliefs about the mind/body problem (reductionism, dualism, interactionism, pragmatism), and that philosophy can aid physicians to be more aware of their beliefs in order to choose the most useful view and to practice coherently

  7. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  8. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline

  9. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  10. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA-huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352, alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole, atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan, brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib, deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate, dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus; Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride; Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL-CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide, landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid, lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab, nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE-3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride, posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide, rupatadine fumarate; Sarizotan hydrochloride, SHL-749

  11. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials reported in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:[188Re]-HDD; A-179578, adalimumab, AK-602, albumin interferon alfa, alfimeprase, amelubant, anakinra, anti-CD2 MAb, APD-356, aripiprazole, atvogen; Bimatoprost, bimosiamose, BLP-25, brivaracetam; Caspofungin acetate, cilansetron, CMV vaccine (bivalent), conivaptan hydrochloride, Cypher; Darbepoetin alfa, darifenacin hydrobromide, D-D4FC, decitabine, dnaJP1, doranidazole, dronedarone hydrochloride; Efalizumab, efaproxiral sodium, emtricitabine, Endeavor, entecavir, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, etravirine, ezetimibe; Fampridine, fenretinide, ferumoxtran-10, forodesine hydrochloride; Gantacurium chloride, gemi-floxacin mesilate, Glyminox, GW-501516; HBV-ISS, hepavir B, human insulin, HuMax-CD20, hyaluronic acid, HyCAMP; Icatibant, IDEA-070, IGN-311, imatinib mesylate, insulin detemir, insulin glargine, insulin glulisine; Lapatinib, lasofoxifene tartrate, LB-80380, liarozole fumarate, liposome encapsulated doxorubicin, lumiracoxib, LY-570310; MC-1, melatonin, merimepodib, metanicotine, midostaurin; Natalizumab, nicotine conjugate vaccine, NYVAC-HIV C; Patupilone, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pelitinib, Peru-15, pexelizumab, PHP, pimecrolimus, prednisolone sodium metasulfobenzoate; Recombinant alfa1-antitrypsin (AAT), retigabine, rHA influenza vaccine, rifalazil, rofecoxib, rosiglitazone maleate/Metformin hydrochloride, rostaporfin, rosuvastatin calcium, rubitecan; Selenite sodium, semilente insulin, SMP-797, sorafenib; Talampanel, tenofovir disoproxil fumarate, TER-199, tiotropium bromide, torcetrapib, treprostinil sodium, TTA

  12. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil

  13. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  14. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin

  15. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com This issue focuses on the following selection of drugs: A-007, A6, adalimumab, adenosine triphosphate, alefacept, alemtuzumab, AllerVax Ragweed, amphora, anakinra, angiotensin-(1-7), anidulafungin, apomine, aripiprazole, atomoxetine hydrochloride, avanafil; BAL-8557, becatecarin, bevacizumab, biphasic insulin aspart, BMS-188797, bortezomib, bosentan, botulinum toxin type B, brivudine; Calcipotriol/betamethasone dipropionate, caspofungin acetate, catumaxomab, certolizumab pegol, cetuximab, CG-0070, ciclesonide, cinacalcet hydrochloride, clindamycin phosphate/benzoyl peroxide, cryptophycin 52, Cypher; Dabigatran etexilate, darapladib, darbepoetin alfa, decitabine, deferasirox, desloratadine, dexanabinol, dextromethorphan/quinidine sulfate, DMF, drotrecogin alfa (activated), duloxetine hydrochloride; E-7010, edaravone, efalizumab, emtricitabine, entecavir, eplerenone, erlotinib hydrochloride, escitalopram oxalate, estradiol valerate/dienogest, eszopiclone, exenatide, ezetimibe; Fondaparinux sodium, fulvestrant; Gefitinib, gestodene, GYKI-16084; Hyaluronic acid, hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, indiplon, insulin glargine; Juzen-taiho-to; Lamivudine/zidovudine/abacavir sulfate, L-arginine hydrochloride, lasofoxifene tartrate, L-BLP-25, lenalidomide, levocetirizine, levodopa/carbidopa/entacapone, lexatumumab, lidocaine/prilocaine, lubiprostone, lumiracoxib; MAb-14.18, mitoquidone; Natalizumab, neridronic acid, neuradiab; Olpadronic acid sodium salt, omalizumab; p53-DC vaccine, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, perifosine, pimecrolimus, prasterone, prasugrel, PRO-2000

  16. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 166Ho-DOTMP, 3-AP; Abatacept, abetimus sodium, ACR-16, adefovir dipivoxil, alefacept, AMD-070, aminolevulinic acid hexyl ester, anatumomab mafenatox, anti-CTLA-4 MAb, antigastrin therapeutic vaccine, AP-12009, AP-23573, APC-8024, aripiprazole, ATL-962, atomoxetine hydrochloride; Bevacizumab, bimatoprost, bortezomib, bosentan, BR-1; Calcipotriol/betamethasone dipropionate, cinacalcet hydrochloride, clofazimine, colchicine, cold-adapted influenza vaccine trivalent, CRM197; Desloratadine, desoxyepothilone B, diethylhomospermine; Edodekin alfa, efalizumab, elcometrine, eletriptan, enfuvirtide, entecavir, EP-2101, eplerenone, erlotinib hydrochloride, etoricoxib, everolimus, exherin, ezetimibe; Febuxostat, fluorescein lisicol, fosamprenavir calcium, frovatriptan; Hemoglobin raffimer, HSPPC-96, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, IRX-2, istradefylline, IV gamma-globulin, ixabepilone; Kahalalide F; L-759274, levodopa/carbidopa/entacapone, licofelone, lonafarnib, lopinavir, lurtotecan, LY-156735; MAb G250, mecasermin, melatonin, midostaurin, muraglitazar; Nesiritide, nitronaproxen; O6-Benzylguanine, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, omapatrilat, oral insulin; Parecoxib sodium, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, peptide YY3-36, PG-CPT, phenoxodiol, pimecrolimus, posaconazole; Rasagiline mesilate, rDNA insulin, RG228, rimonabant hydrochloride, rosuvastatin calcium, rotigotine hydrochloride; S-3304, safinamide mesilate, salcaprozic acid sodium salt, SDZ-SID-791, SGN-30, soblidotin

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  18. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus

  19. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed

  1. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil, AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant, aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost, bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003, darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E-5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101, enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride, escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium; Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG; Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride, ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor; Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY-307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus, pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV-701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine, rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate

  2. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X

    2008-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir

  3. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  4. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  5. Shared clinical decision making

    PubMed Central

    AlHaqwi, Ali I.; AlDrees, Turki M.; AlRumayyan, Ahmad; AlFarhan, Ali I.; Alotaibi, Sultan S.; AlKhashan, Hesham I.; Badri, Motasim

    2015-01-01

    Objectives: To determine preferences of patients regarding their involvement in the clinical decision making process and the related factors in Saudi Arabia. Methods: This cross-sectional study was conducted in a major family practice center in King Abdulaziz Medical City, Riyadh, Saudi Arabia, between March and May 2012. Multivariate multinomial regression models were fitted to identify factors associated with patients preferences. Results: The study included 236 participants. The most preferred decision-making style was shared decision-making (57%), followed by paternalistic (28%), and informed consumerism (14%). The preference for shared clinical decision making was significantly higher among male patients and those with higher level of education, whereas paternalism was significantly higher among older patients and those with chronic health conditions, and consumerism was significantly higher in younger age groups. In multivariate multinomial regression analysis, compared with the shared group, the consumerism group were more likely to be female [adjusted odds ratio (AOR) =2.87, 95% confidence interval [CI] 1.31-6.27, p=0.008] and non-dyslipidemic (AOR=2.90, 95% CI: 1.03-8.09, p=0.04), and the paternalism group were more likely to be older (AOR=1.03, 95% CI: 1.01-1.05, p=0.04), and female (AOR=2.47, 95% CI: 1.32-4.06, p=0.008). Conclusion: Preferences of patients for involvement in the clinical decision-making varied considerably. In our setting, underlying factors that influence these preferences identified in this study should be considered and tailored individually to achieve optimal treatment outcomes. PMID:26620990

  6. Are Clinical Studies for You?

    MedlinePlus

    ... Page > Participate in Clinical Studies If you are thinking about participating in a Clinical Study at NIH, ... medical care and activities of daily living. In thinking about the risks of research, it is helpful ...

  7. Rare Diseases Clinical Research Network

    MedlinePlus

    ... RDCRN? Aims of the Rare Diseases Clinical Research Network Contact Us RDCRN Members Login Accessibility Disclaimer The Rare Diseases Clinical Research Network is an initiative of the Office of Rare ...

  8. Gaining approval for clinical research.

    PubMed

    Cobb, Vanessa; Srinivasan, Neil; Lambiase, Pier

    2016-07-01

    Set-up and delivery of a clinical research project can be complicated and difficult. This article introduces the regulatory processes involved in gaining approval for clinical research and discusses the obstacles that may be encountered. PMID:27388381

  9. Clinical applications of angiocardiography

    NASA Technical Reports Server (NTRS)

    Dodge, H. T.; Sandler, H.

    1974-01-01

    Several tables are presented giving left ventricular (LV) data for normal patients and patients with heart disease of varied etiologies, pointing out the salient features. Graphs showing LV pressure-volume relationships (compliance) are presented and discussed. The method developed by Rackley et al. (1964) for determining left ventricular mass in man is described, and limitations to the method are discussed. Some clinical methods for determining LV oxygen consumption are briefly described, and the relation of various abnormalities of ventricular performance to coronary artery disease and ischemic heart disease is characterized.

  10. Likelihood and clinical trials.

    PubMed

    Hill, G; Forbes, W; Kozak, J; MacNeill, I

    2000-03-01

    The history of the application of statistical theory to the analysis of clinical trials is reviewed. The current orthodoxy is a somewhat illogical hybrid of the original theory of significance tests of Edgeworth, Karl Pearson, and Fisher, and the subsequent decision theory approach of Neyman, Egon Pearson, and Wald. This hegemony is under threat from Bayesian statisticians. A third approach is that of likelihood, stemming from the work of Fisher and Barnard. This approach is illustrated using hypothetical data from the Lancet articles by Bradford Hill, which introduced clinicians to statistical theory. PMID:10760630

  11. Gorham's disease: clinical case.

    PubMed

    Sá, Pedro; Marques, Pedro; Oliveira, Carolina; Rodrigues, André Sá; Amorim, Nelson; Pinto, Rui

    2015-01-01

    Gorham's disease, also known as idiopathic massive osteolysis, is a rare pathological condition characterized by vascular proliferation that results in destruction and reabsorption of the bone matrix, of unknown etiology. It was first described by Jackson in 1838, but it was Gorham and Stout, in 1955, who defined this disease as a specific entity. It has variable clinical presentation and generally has progressive behavior. Controversy continues regarding the treatment and there is no standard treatment. This pathological condition generally presents a favorable prognosis. Here, a case of Gorham's disease with involvement of the left hip is presented, in a male patient without relevant antecedents.

  12. [Rickettsiosis: a clinical approach].

    PubMed

    Boillat, N; Greub, G

    2007-05-16

    Rickettsiosis are zoonotic diseases transmitted to humans by arthropods. Prevalence of imported disease increases in parallel to the frequency of international travel. Clinical presentation is characterised by fever, headache and rash. Delay in the initiation of an antibiotic treatment efficient on Rickettsia spp. may have fatal impact on evolution. Serology is the more widely used diagnostic test. However, it only provides retrospective diagnosis. Polymerase chain reaction (PCR) and immunohistochemistry may provide early diagnosis. Doxycyclin is the first-line treatment and should be given empirically as soon as a rickettsial disease is suspected. PMID:17585624

  13. Gorham's disease: clinical case☆

    PubMed Central

    Sá, Pedro; Marques, Pedro; Oliveira, Carolina; Rodrigues, André Sá; Amorim, Nelson; Pinto, Rui

    2015-01-01

    Gorham's disease, also known as idiopathic massive osteolysis, is a rare pathological condition characterized by vascular proliferation that results in destruction and reabsorption of the bone matrix, of unknown etiology. It was first described by Jackson in 1838, but it was Gorham and Stout, in 1955, who defined this disease as a specific entity. It has variable clinical presentation and generally has progressive behavior. Controversy continues regarding the treatment and there is no standard treatment. This pathological condition generally presents a favorable prognosis. Here, a case of Gorham's disease with involvement of the left hip is presented, in a male patient without relevant antecedents. PMID:26229923

  14. Clinical trials in India.

    PubMed

    Maiti, Rituparna; M, Raghavendra

    2007-07-01

    The concept of outsourcing for the development and global studies on new drugs has become widely accepted in the pharmaceutical industry due to its cost and uncertainty. India is going to be the most preferred location for contract pharma research and development due to its huge treatment naïve population, human resources, technical skills, adoption/amendment/implementation of rules/laws by regulatory authorities, and changing economic environment. But still 'miles to go' to fulfill the pre-requisites to ensure India's success. In spite of all the pitfalls, the country is ambitious and optimist to attract multinational pharmaceutical companies to conduct their clinical trials in India.

  15. Aphasia in Clinical Practice

    PubMed Central

    Kertesz, Andrew

    1983-01-01

    Aphasia is a central language impairment with word finding and comprehension deficit and paraphasias. The highlights of the essential language tests and the classification based on a scorable assessment are presented. The clinical syndromes of Broca's, global, Wernicke, conduction, anomic and transcortical aphasias are detailed with definition, localization, and prognosis. Modality specific disorders associated with aphasic syndromes are discussed. The management of the aphasic patient, consisting of informed support and coordination of available services, is often the responsibility of the family physician. ImagesFig. 1Fig. 2 PMID:21286589

  16. Clinical pharmacology of thalidomide.

    PubMed

    Trapnell, C B

    1998-01-01

    Thalidomide is being investigated for its potential use in treating HIV wasting syndrome and other HIV-related conditions. Thalidomide is primarily broken down by hydrolysis; however, the metabolite responsible for its clinical effect is unknown. The optimum concentration of thalidomide or its metabolites to maximize benefits while minimizing toxicities is also unknown. Once daily administration is feasible because of thalidomide's 14- to 18-hour half-life. Because of thalidomide's known potential for causing birth defects, pregnant women are cautioned not to take the drug. One of the two thalidomide stereoisomers was presumed to be responsible for teratogenicity; trials using each isomer individually do not support this notion.

  17. Clinical management of agnosia.

    PubMed

    Burns, Martha S

    2004-01-01

    Agnosia is a neurological recognition deficit that affects a single modality. Visual agnosias include pure object agnosia, prosopagnosia, akinetopsia, and pure alexia. Auditory agnosias include pure word deafness, phonagnosia, and pure sound agnosia. New neuroimaging tools have permitted scientists to better understand the loci of lesions that cause various agnosias and from that knowledge to develop theories about the processing networks that contribute to perception and recognition in each modality. These research data, in turn, inform the rehabilitation process. By utilizing current knowledge about neuroprocessing networks, clinical professionals can differentially diagnose agnosias from aphasia and other cognitive deficits. Practical approaches to treatment of agnosia will follow once the diagnosis is established.

  18. Clinical thinking in psychiatry.

    PubMed

    Wells, Lloyd A

    2015-06-01

    I discuss the lack of precision in the term 'clinical reasoning' and its relationship to evidence-based medicine and critical thinking. I examine critical thinking skills, their underemphasis in medical education and successful attempts to remediate them. Evidence-based medicine (and evidence-based psychiatry) offer much but are hampered by the ubiquity and flaws of meta-analysis. I explore views of evidence-based medicine among psychiatry residents, as well as capacity for critical thinking in residents before and after a course in philosophy. I discuss decision making by experienced doctors and suggest possible futures of this issue.

  19. Clinical digital photography: implementation of clinical photography for everyday practice.

    PubMed

    Shorey, Robert; Moore, Kenneth

    2009-03-01

    Clinical photography requires a regimented system of image acquisition similar to the regimentation needed for dental radiographs. Clinical digital photographic equipment is rapidly advancing. To achieve the best image quality and resolution, digital single-lens reflex systems are necessary. DSLR clinical systems are made of three components: camera body, macro lens, and flash attachment. Other ancillary equipment is necessary to achieve appropriate clinical image reveals and composition. Recommendations are given to assist in the implementation of clinical photography in the dental practice. PMID:19830983

  20. Developing a clinical research career.

    PubMed

    Nicholson, Caroline

    The National Institute for Health Research helps to promote clinical research careers for health professionals working in clinical practice, and has developed a structure to support new researchers. This article explains how nurses can get involved in clinical research and the support available to them. PMID:27491187