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Peter Hawkey - One of the best experts on this subject based on the ideXlab platform.

  • multidrug resistant gram negative bacteria a product of globalization
    Journal of Hospital Infection, 2015
    Co-Authors: Peter Hawkey
    Abstract:

    Global trade and mobility of people has increased rapidly over the last 20 years. This has had profound consequences for the evolution and the movement of antibiotic resistance genes. There is increasing exposure of populations all around the world to resistant bacteria arising in the emerging economies. Arguably the most important development of the last two decades in the field of antibiotic resistance is the emergence and spread of extended-spectrum β-lactamases (ESBLs) of the CTX-M group. A consequence of the very high rates of ESBL production among Enterobacteriaceae in Asian countries is that there is a substantial use of Carbapenem Antibiotics, resulting in the emergence of plasmid-mediated resistance to Carbapenems. This article reviews the emergence and spread of multidrug-resistant Gram-negative bacteria, focuses on three particular Carbapenemases ‒ imipenem Carbapenemases, Klebsiella pneumoniae Carbapenemase, and New Delhi metallo-β-lactamase ‒ and highlights the importance of control of antibiotic use.

Gianfranco Amicosante - One of the best experts on this subject based on the ideXlab platform.

  • The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-beta-lactamase enzyme CphA.
    Antimicrobial agents and chemotherapy, 1995
    Co-Authors: Shoshana Keynan, Nigel M. Hooper, Antonio Felici, Gianfranco Amicosante, Andanthony J. Turner
    Abstract:

    The Aeromonas hydrophila AE036 chromosome contains a cphA gene encoding a metallo-beta-lactamase which is highly active against Carbapenem Antibiotics such as imipenem. Here we show that the cphA gene product shares inhibitory similarities with a mammalian zinc peptidase, membrane dipeptidase (MDP; dehydropeptidase I). Both enzymes are able to hydrolyze imipenem and are inhibited by cilastatin. The active site similarities of these enzymes are not reflected in any significant primary sequence similarity.

  • High specificity of cphA-encoded metallo-beta-lactamase from Aeromonas hydrophila AE036 for Carbapenems and its contribution to beta-lactam resistance.
    Antimicrobial agents and chemotherapy, 1993
    Co-Authors: Bernardetta Segatore, Giuseppe Satta, Orietta Massidda, Domenico Setacci, Gianfranco Amicosante
    Abstract:

    The Aeromonas hydrophila AE036 chromosome contains a cphA gene encoding a metallo-beta-lactamase highly active against Carbapenem Antibiotics. This enzyme was induced in strain AE036 to the same extent by both benzylpenicillin and imipenem. When the cphA gene was inserted into plasmid pACYC184, used to transform Escherichia coli DH5 alpha, the MICs of imipenem, meropenem, and penem HRE664 for recombinant clone DH5 alpha(pAA20R), expressing the Aeromonas metallo-beta-lactamase, were significantly increased, but those of penicillins and cephalosporins were not. When the metallo-beta-lactamase purified from E. coli DH5 alpha(pAA20R) was assayed with several beta-lactam substrates, it hydrolyzed Carbapenems but not penicillins or cephalosporins efficiently. These results demonstrate that this metallo-beta-lactamase possesses an unusual spectrum of activity compared with all the other class B enzymes identified so far, being active on penems and Carbapenems only. This enzyme may thus contribute to the development of resistance to penems and Carbapenems but not other beta-lactams.

Renuka Heddurshetti - One of the best experts on this subject based on the ideXlab platform.

  • molecular epidemiology and mechanisms of Carbapenem resistance in acinetobacter baumannii endemic in new york city
    Clinical Infectious Diseases, 2003
    Co-Authors: John Quale, Simona Bratu, David Landman, Renuka Heddurshetti
    Abstract:

    Multidrug-resistant Acinetobacter baumannii has emerged as a serious nosocomial pathogen in certain areas. In Brooklyn, New York, citywide surveillance revealed that ∼2 of every 3 isolates were resistant to Carbapenem Antibiotics. Genetic fingerprinting revealed that 2 strains accounted for 82% of these resistant isolates. Compared with Carbapenem-susceptible isolates, Carbapenem-resistant isolates had reduced expression of 47-, 44-, and 37-kDa outer-membrane proteins. No specific Carbapenemase was found; however, Carbapenem-resistant isolates expressed greater levels of a class C cephalosporinase. Although expression of penicillin-binding proteins varied among strains, no consistent pattern appeared to account for Carbapenem resistance. An efflux pump, present in several strains, did not appear to contribute to Carbapenem resistance. Clonal spread of Carbapenem-resistant A. baumannii has occurred in hospitals in Brooklyn. The preliminary findings for a small number of strains suggest that diminished production of outer-membrane porins, together with increased expression of a class C cephalosporinase, appear to be important factors leading to Carbapenem resistance in this region.

  • molecular epidemiology and mechanisms of Carbapenem resistance in acinetobacter baumannii endemic in new york city
    Clinical Infectious Diseases, 2003
    Co-Authors: John Quale, Simona Bratu, David Landman, Renuka Heddurshetti
    Abstract:

    Multidrug-resistant Acinetobacter baumannii has emerged as a serious nosocomial pathogen in certain areas. In Brooklyn, New York, citywide surveillance revealed that approximately 2 of every 3 isolates were resistant to Carbapenem Antibiotics. Genetic fingerprinting revealed that 2 strains accounted for 82% of these resistant isolates. Compared with Carbapenem-susceptible isolates, Carbapenem-resistant isolates had reduced expression of 47-, 44-, and 37-kDa outer-membrane proteins. No specific Carbapenemase was found; however, Carbapenem-resistant isolates expressed greater levels of a class C cephalosporinase. Although expression of penicillin-binding proteins varied among strains, no consistent pattern appeared to account for Carbapenem resistance. An efflux pump, present in several strains, did not appear to contribute to Carbapenem resistance. Clonal spread of Carbapenem-resistant A. baumannii has occurred in hospitals in Brooklyn. The preliminary findings for a small number of strains suggest that diminished production of outer-membrane porins, together with increased expression of a class C cephalosporinase, appear to be important factors leading to Carbapenem resistance in this region.

Eiko Suzuki - One of the best experts on this subject based on the ideXlab platform.

  • observation of clinically relevant drug interaction in chimeric mice with humanized livers the case of valproic acid and Carbapenem Antibiotics
    European Journal of Drug Metabolism and Pharmacokinetics, 2017
    Co-Authors: Eiko Suzuki, Kumiko Koyama, Daisuke Nakai, Ryoya Goda, Hiroshi Kuga, Kan Chiba
    Abstract:

    Background and Objective Human in vitro and dog in vitro/in vivo researches indicate that the drug–drug interaction (DDI) of decreased plasma valproic acid (VPA) concentration by co-administration of Carbapenem Antibiotics is caused by inhibition of acylpeptide hydrolase (APEH)-mediated VPA acylglucuronide (VPA-G) hydrolysis by Carbapenems. In this study, we investigated VPA disposition and APEH activities in TK-NOG chimeric mice, whose livers were highly replaced with human hepatocytes, to evaluate the utility of this animal model and the clinical relevance of the DDI mechanism.

  • inhibition mechanism of Carbapenem Antibiotics on acylpeptide hydrolase a key enzyme in the interaction with valproic acid
    Xenobiotica, 2011
    Co-Authors: Eiko Suzuki, Daisuke Nakai, Naotoshi Yamamura, Nobuhiro Kobayashi, Osamu Okazaki, Takashi Izumi
    Abstract:

    We have reported that inhibition of acylpeptide hydrolase (APEH), identified as valproic acid glucuronide hydrolase in human liver cytosol, by Carbapenem Antibiotics could lead to a decrease of plasma levels of valproic acid. In this study, we examined the inhibition mechanism using human liver cytosol and purified porcine APEH with a similar property to human counterpart.After preincubation of human liver cytosol with panipenem or meropenem for 30 min, the inhibition of APEH activity was 20-fold stronger than that without preincubation. Porcine APEH activity inhibited by meropenem did not recover after dialysis. Meropenem bound to porcine APEH and the binding was blocked by a serine hydrolase inhibitor, diisopropyl fluorophosphate.Open β-lactam ring form of meropenem did not affect APEH activity in human liver cytosol. Likewise, other Antibiotics, which have a different heterocycle adjacent to the β-lactam ring with an opposite configuration of the side chain from Carbapenems, did not inhibit APEH activi...

  • identification of valproic acid glucuronide hydrolase as a key enzyme for the interaction of valproic acid with Carbapenem Antibiotics
    Drug Metabolism and Disposition, 2010
    Co-Authors: Eiko Suzuki, Daisuke Nakai, Naotoshi Yamamura, Nobuhiro Kobayashi, Yuji Ogura, Kazuishi Kubota, Shinichi Miura, Osamu Okazaki
    Abstract:

    Plasma levels of valproic acid (VPA) are decreased by concomitant use with Carbapenem Antibiotics, such as panipenem (PAPM). One of the plausible mechanisms of this interaction is the inhibition of VPA glucuronide (VPA-G) hydrolysis by Carbapenems in the liver. To elucidate this interaction mechanism, we purified VPA-G hydrolase from human liver cytosol, in which the hydrolytic activity was mainly located. After chromatographic purification, the VPA-G hydrolase was identified as acylpeptide hydrolase (APEH). APEH-depleted cytosol, prepared by an immunodepletion method, completely lacked the hydrolytic activity. These results demonstrate that APEH is a single enzyme involved in PAPM-sensitive VPA-G hydrolysis in cytosol. In addition, the hydrolytic activity of recombinant human APEH was inhibited by PAPM and the inhibition profile by typical esterase inhibitors (diisopropyl fluorophosphate, 5,5'-dithiobis(2-nitrobenzoic acid), p-chloromercuribenzoic acid, and d-saccharic acid 1,4-lactone) was similar to that of human liver cytosol. Cytosolic VPA-G hydrolase activity was slightly inhibited by cholinesterase and carboxylesterase inhibitors. beta-Glucuronidase activity remained in APEH-depleted cytosol, whereas VPA-G hydrolase activity was completely abolished. Thus, either cholinesterase, carboxylesterase, or beta-glucuronidase in cytosol would not be involved in VPA-G hydrolysis. Taken together, APEH plays a major role in the PAPM-sensitive VPA-G hydrolysis in the liver. These findings suggest that APEH could be a key enzyme for the drug interaction of VPA with Carbapenems via VPA-G hydrolysis.

  • Identification of Valproic Acid Glucuronide Hydrolase As a Key Enzyme for the Interaction of Valproic Acid with Carbapenem Antibiotics
    2010
    Co-Authors: Eiko Suzuki, Daisuke Nakai, Naotoshi Yamamura, Yuji Ogura, Kazuishi Kubota
    Abstract:

    Plasma levels of valproic acid (VPA) are decreased by concomitant use with Carbapenem Antibiotics, such as panipenem (PAPM). One of the plausible mechanisms of this interaction is the inhibition of VPA glucuronide (VPA-G) hydrolysis by Carbapenems in the liver. To elucidate this interaction mechanism, we purified VPA-G hydro-lase from human liver cytosol, in which the hydrolytic activity was mainly located. After chromatographic purification, the VPA-G hy-drolase was identified as acylpeptide hydrolase (APEH). APEH-depleted cytosol, prepared by an immunodepletion method, com-pletely lacked the hydrolytic activity. These results demonstrate that APEH is a single enzyme involved in PAPM-sensitive VPA-G hydrolysis in cytosol. In addition, the hydrolytic activity of recom-binant human APEH was inhibited by PAPM and the inhibition profile by typical esterase inhibitors (diisopropyl fluorophosphate, 5,5-dithiobis(2-nitrobenzoic acid), p-chloromercuribenzoic acid, and D-saccharic acid 1,4-lactone) was similar to that of human liver cytosol. Cytosolic VPA-G hydrolase activity was slightly inhibited by cholinesterase and carboxylesterase inhibitors. -Glucuroni-dase activity remained in APEH-depleted cytosol, whereas VPA-G hydrolase activity was completely abolished. Thus, either cholines-terase, carboxylesterase, or -glucuronidase in cytosol would not be involved in VPA-G hydrolysis. Taken together, APEH plays a major role in the PAPM-sensitive VPA-G hydrolysis in the liver. These findings suggest that APEH could be a key enzyme for the drug interaction of VPA with Carbapenems via VPA-G hydrolysis

Xavier Bertrand - One of the best experts on this subject based on the ideXlab platform.

  • which non Carbapenem Antibiotics are active against extended spectrum β lactamase producing enterobacteriaceae
    International Journal of Antimicrobial Agents, 2018
    Co-Authors: Helene Bouxom, Damien Fournier, Kevin Bouiller, Didier Hocquet, Xavier Bertrand
    Abstract:

    In this study, the activity of 18 non-Carbapenem Antibiotics was evaluated against 100 extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-Ec) and 50 ESBL-producing Klebsiella pneumoniae (ESBL-Kp) isolated from urinary tract infections and bacteraemia in 2016. Minimum inhibitory concentrations (MICs) were determined using reference methods and the susceptibility profiles were defined according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2017 recommendations. All of the ESBL-Ec isolates were susceptible to ceftazidime/avibactam and a great majority of them were susceptible to fosfomycin (98%), piperacillin/tazobactam (97%), amikacin (97%) and nitrofurantoin (96%). Mecillinam, cefoxitin and ceftolozane/tazobactam remained active against 92%, 83% and 78% of the ESBL-Ec isolates, respectively. Moreover, 100%, 94% and 90% of the ESBL-Kp tested were susceptible to ceftazidime/avibactam, amikacin and mecillinam, respectively. This study showed that there are non-Carbapenem options (including orally administrable drugs) for the treatment of all of the situations of ESBL-Ec or ESBL-Kp infections, with ceftazidime/avibactam being the most efficient alternative.