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6. Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance

Author

Frenk, Sammy, Temkin, Elizabeth, Lurie-Weinberger, Mor N., Keren-Paz, Alona, Rov, Reut, Rakovitsky, Nadya, Wullfhart, Liat, Nutman, Amir, Daikos, George L., Skiada, Anna, Durante-Mangoni, Emanuele, Benattar, Yael Dishon, Bitterman, Roni, Yahav, Dafna, Daitch, Vered, Bernardo, Mariano, Iossa, Domenico, Zusman, Oren, Friberg, Lena, Mouton, Johan W., Theuretzbacher, Ursula, Leibovici, Leonard, Geffen, Yuval, Gershon, Rina, Paul, Mical, Carmeli, Yehuda, Frenk, Sammy, Temkin, Elizabeth, Lurie-Weinberger, Mor N., Keren-Paz, Alona, Rov, Reut, Rakovitsky, Nadya, Wullfhart, Liat, Nutman, Amir, Daikos, George L., Skiada, Anna, Durante-Mangoni, Emanuele, Benattar, Yael Dishon, Bitterman, Roni, Yahav, Dafna, Daitch, Vered, Bernardo, Mariano, Iossa, Domenico, Zusman, Oren, Friberg, Lena, Mouton, Johan W., Theuretzbacher, Ursula, Leibovici, Leonard, Geffen, Yuval, Gershon, Rina, Paul, Mical, and Carmeli, Yehuda

Abstract

Objectives: To describe the population genetics and antibiotic resistance gene distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates causing infections in three Mediterranean countries. Methods: Isolates were collected during the 2013-17 AIDA clinical trial in six hospitals in Israel, Greece and Italy. WGS, bioinformatic characterization and antibiotic resistance profiling were performed. Results In the 247 CRAB isolates characterized in this study, ST distribution varied by country: 29/31 (93.5%) Greek isolates, 34/41 (82.9%) Italian isolates and 70/175 (40.0%) Israeli isolates belonged to ST2. The identified ST2 isolates included eight distinct clades: 2C, 2D and 2H were significantly more common in Italy, while 2F was unique to Greece. The uncommon ST3 was not present among Greek isolates and constituted only 5/41 (12%) Italian isolates. On the other hand, it was much more common among Israeli isolates: 78/175 (44.6%) belonged to ST3. The vast majority of isolates, 240/247 (97.2%), were found to harbour acquired carbapenemases, primarily bla(OXA-23.) The chromosomal oxaAb (bla(OXA-51-like)) and ampC genes characteristic of this organism were also ubiquitous. Most (96.4%) ST3 isolates carried a broad-host-range plasmid IncP1 alpha. Conclusions The geographical differences in CRAB populations support the theory that clonal spread of CRAB leads to endemicity in hospitals and regions. The close association between antibiotic resistance genes and clades, and between plasmids and STs, suggest that de novo creation of MDR A. baumannii is rare. The clustering of antibiotic resistance genes and plasmids that is unique to each clade/ST, and nearly uniform within clades/STs, suggests that horizontal transmission is rare but crucial to the clade's/ST's success.

Published
2022
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7. Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance

Author

Frenk, Sammy Temkin, Elizabeth Lurie-Weinberger, Mor N. Keren-Paz, Alona Rov, Reut Rakovitsky, Nadya Wullfhart, Liat Nutman, Amir Daikos, George L. Skiada, Anna Durante-Mangoni, Emanuele Dishon Benattar, Yael Bitterman, Roni Yahav, Dafna Daitch, Vered Bernardo, Mariano Iossa, Domenico Zusman, Oren Friberg, Lena E. Mouton, Johan W. Theuretzbacher, Ursula Leibovici, Leonard Geffen, Yuval Gershon, Rina Paul, Mical Carmeli, Yehuda

Abstract

OBJECTIVES: To describe the population genetics and antibiotic resistance gene distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates causing infections in three Mediterranean countries. METHODS: Isolates were collected during the 2013-17 AIDA clinical trial in six hospitals in Israel, Greece and Italy. WGS, bioinformatic characterization and antibiotic resistance profiling were performed. RESULTS: In the 247 CRAB isolates characterized in this study, ST distribution varied by country: 29/31 (93.5%) Greek isolates, 34/41 (82.9%) Italian isolates and 70/175 (40.0%) Israeli isolates belonged to ST2. The identified ST2 isolates included eight distinct clades: 2C, 2D and 2H were significantly more common in Italy, while 2F was unique to Greece. The uncommon ST3 was not present among Greek isolates and constituted only 5/41 (12%) Italian isolates. On the other hand, it was much more common among Israeli isolates: 78/175 (44.6%) belonged to ST3. The vast majority of isolates, 240/247 (97.2%), were found to harbour acquired carbapenemases, primarily blaOXA-23. The chromosomal oxaAb (blaOXA-51-like) and ampC genes characteristic of this organism were also ubiquitous. Most (96.4%) ST3 isolates carried a broad-host-range plasmid IncP1α. CONCLUSIONS: The geographical differences in CRAB populations support the theory that clonal spread of CRAB leads to endemicity in hospitals and regions. The close association between antibiotic resistance genes and clades, and between plasmids and STs, suggest that de novo creation of MDR A. baumannii is rare. The clustering of antibiotic resistance genes and plasmids that is unique to each clade/ST, and nearly uniform within clades/STs, suggests that horizontal transmission is rare but crucial to the clade’s/ST’s success.

Published
2022

8. Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance

Author

Frenk, Sammy, primary, Temkin, Elizabeth, additional, Lurie-Weinberger, Mor N., additional, Keren-Paz, Alona, additional, Rov, Reut, additional, Rakovitsky, Nadya, additional, Wullfhart, Liat, additional, Nutman, Amir, additional, Daikos, George L., additional, Skiada, Anna, additional, Durante-Mangoni, Emanuele, additional, Dishon Benattar, Yael, additional, Bitterman, Roni, additional, Yahav, Dafna, additional, Daitch, Vered, additional, Bernardo, Mariano, additional, Iossa, Domenico, additional, Zusman, Oren, additional, Friberg, Lena E., additional, Mouton, Johan W., additional, Theuretzbacher, Ursula, additional, Leibovici, Leonard, additional, Geffen, Yuval, additional, Gershon, Rina, additional, Paul, Mical, additional, and Carmeli, Yehuda, additional

Published
2022
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11. Increased Capsule Thickness and Hypermotility Are Traits of Carbapenem-Resistant Acinetobacter baumannii ST3 Strains Causing Fulminant Infection

Author

Rakovitsky, Nadya, primary, Lellouche, Jonathan, additional, Ben David, Debby, additional, Frenk, Sammy, additional, Elmalih, Polet, additional, Weber, Gabriel, additional, Kon, Hadas, additional, Schwartz, David, additional, Wolfhart, Liat, additional, Temkin, Elizabeth, additional, and Carmeli, Yehuda, additional

Published
2021
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14. A multi-institutional outbreak of New Delhi metallo-β-lactamase–producing Escherichia coli with subsequent acquisition of the Klebsiella pneumoniae carbapenemase gene

Author

Solter, Ester, primary, Kwong, Jason C., additional, Walton, Aaron, additional, Sherry, Norelle, additional, Howden, Benjamin P., additional, Grayson, M. Lindsay, additional, Schwartz, David, additional, Temkin, Elizabeth, additional, Frenk, Sammy, additional, Carmeli, Yehuda, additional, and Schwaber, Mitchell J., additional

Published
2020
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15. Investigation of Outbreaks of Extended-Spectrum Beta-Lactamase-Producing Klebsiella Pneumoniae in Three Neonatal Intensive Care Units Using Whole Genome Sequencing

Author

Frenk, Sammy, primary, Rakovitsky, Nadya, additional, Temkin, Elizabeth, additional, Schechner, Vered, additional, Cohen, Regev, additional, Kloyzner, Bat Sheva, additional, Schwaber, Mitchell J., additional, Solter, Ester, additional, Cohen, Shoshana, additional, Stepansky, Sarit, additional, and Carmeli, Yehuda, additional

Published
2020
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16. Fourier Transform Infrared Spectroscopy Is a New Option for Outbreak Investigation: a Retrospective Analysis of an Extended-Spectrum-Beta-Lactamase-Producing Klebsiella pneumoniae Outbreak in a Neonatal Intensive Care Unit

Author

Rakovitsky, Nadya, primary, Frenk, Sammy, additional, Kon, Hadas, additional, Schwartz, David, additional, Temkin, Elizabeth, additional, Solter, Ester, additional, Paikin, Svetlana, additional, Cohen, Regev, additional, Schwaber, Mitchell J., additional, Carmeli, Yehuda, additional, and Lellouche, Jonathan, additional

Published
2020
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18. A multi-institutional outbreak of New Delhi metallo-β-lactamase–producing Escherichia coliwith subsequent acquisition of the Klebsiella pneumoniaecarbapenemase gene

Author

Solter, Ester, Kwong, Jason C., Walton, Aaron, Sherry, Norelle, Howden, Benjamin P., Grayson, M. Lindsay, Schwartz, David, Temkin, Elizabeth, Frenk, Sammy, Carmeli, Yehuda, and Schwaber, Mitchell J.

Abstract

AbstractWe characterized 57 isolates from a 2-phase clonal outbreak of New Delhi metallo-β-lactamase–producing Eschericha coli, involving 9 Israeli hospitals; all but 1 isolate belonged to sequence-type (ST) 410. Most isolates in the second phase harbored blaKPC-2in addition to blaNDM-5. Genetic sequencing revealed most dual-carbapenemase–producing isolates to be monophyletically derived from a common ancestor.

Published
2021
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24. Fourier Transform Infrared Spectroscopy Is a New Option for Outbreak Investigation: a Retrospective Analysis of an Extended-Spectrum-Beta-Lactamase-Producing Klebsiella pneumoniaeOutbreak in a Neonatal Intensive Care Unit

Author

Rakovitsky, Nadya, Frenk, Sammy, Kon, Hadas, Schwartz, David, Temkin, Elizabeth, Solter, Ester, Paikin, Svetlana, Cohen, Regev, Schwaber, Mitchell J., Carmeli, Yehuda, and Lellouche, Jonathan

Abstract

The IR Biotyper is a new automated typing system based on Fourier-transform infrared (FT-IR) spectroscopy that gives results within 4 h. We aimed (i) to use the IR Biotyper to retrospectively analyze an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae(ESBL-KP) in a neonatal intensive care unit and to compare results to BOX-PCR and whole-genome sequencing (WGS) results as the gold standard and (ii) to assess how the cutoff values used to define clusters affect the discriminatory power of the IR Biotyper.

Published
2020
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25. Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance

Author

Sammy Frenk, Elizabeth Temkin, Mor N. Lurie-Weinberger, Alona Keren-Paz, Reut Rov, Nadya Rakovitsky, Liat Wullfhart, Amir Nutman, George L. Daikos, Anna Skiada, Emanuele Durante-Mangoni, Yael Dishon Benattar, Roni Bitterman, Dafna Yahav, Vered Daitch, Mariano Bernardo, Domenico Iossa, Oren Zusman, Lena E. Friberg, Johan W. Mouton, Ursula Theuretzbacher, Leonard Leibovici, Yuval Geffen, Rina Gershon, Mical Paul, Yehuda Carmeli, Frenk, Sammy, Temkin, Elizabeth, Lurie-Weinberger, Mor N, Keren-Paz, Alona, Rov, Reut, Rakovitsky, Nadya, Wullfhart, Liat, Nutman, Amir, Daikos, George L, Skiada, Anna, Durante-Mangoni, Emanuele, Dishon Benattar, Yael, Bitterman, Roni, Yahav, Dafna, Daitch, Vered, Bernardo, Mariano, Iossa, Domenico, Zusman, Oren, Friberg, Lena E, Mouton, Johan W, Theuretzbacher, Ursula, Leibovici, Leonard, Geffen, Yuval, Gershon, Rina, Paul, Mical, and Carmeli, Yehuda

Subjects
Pharmacology, Microbiology (medical), Acinetobacter baumannii, Microbial Sensitivity Tests, beta-Lactamases, Anti-Bacterial Agents, Infectious Diseases, Bacterial Proteins, Carbapenems, Drug Resistance, Multiple, Bacterial, Humans, Pharmacology (medical), Acinetobacter Infections, Multilocus Sequence Typing
Abstract

Objectives To describe the population genetics and antibiotic resistance gene distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates causing infections in three Mediterranean countries. Methods Isolates were collected during the 2013–17 AIDA clinical trial in six hospitals in Israel, Greece and Italy. WGS, bioinformatic characterization and antibiotic resistance profiling were performed. Results In the 247 CRAB isolates characterized in this study, ST distribution varied by country: 29/31 (93.5%) Greek isolates, 34/41 (82.9%) Italian isolates and 70/175 (40.0%) Israeli isolates belonged to ST2. The identified ST2 isolates included eight distinct clades: 2C, 2D and 2H were significantly more common in Italy, while 2F was unique to Greece. The uncommon ST3 was not present among Greek isolates and constituted only 5/41 (12%) Italian isolates. On the other hand, it was much more common among Israeli isolates: 78/175 (44.6%) belonged to ST3. The vast majority of isolates, 240/247 (97.2%), were found to harbour acquired carbapenemases, primarily blaOXA-23. The chromosomal oxaAb (blaOXA-51-like) and ampC genes characteristic of this organism were also ubiquitous. Most (96.4%) ST3 isolates carried a broad-host-range plasmid IncP1α. Conclusions The geographical differences in CRAB populations support the theory that clonal spread of CRAB leads to endemicity in hospitals and regions. The close association between antibiotic resistance genes and clades, and between plasmids and STs, suggest that de novo creation of MDR A. baumannii is rare. The clustering of antibiotic resistance genes and plasmids that is unique to each clade/ST, and nearly uniform within clades/STs, suggests that horizontal transmission is rare but crucial to the clade’s/ST’s success.

Published
2021

26. A multi-institutional outbreak of New Delhi metallo-β-lactamase-producing Escherichia coli with subsequent acquisition of the Klebsiella pneumoniae carbapenemase gene.

Author

Solter E, Kwong JC, Walton A, Sherry N, Howden BP, Grayson ML, Schwartz D, Temkin E, Frenk S, Carmeli Y, and Schwaber MJ

Subjects
Anti-Bacterial Agents pharmacology, Bacterial Proteins, Escherichia coli genetics, Escherichia coli Infections epidemiology, Humans, Israel epidemiology, beta-Lactamases, Disease Outbreaks, Escherichia coli isolation & purification, Escherichia coli Infections microbiology, Klebsiella pneumoniae enzymology, Klebsiella pneumoniae genetics
Abstract

We characterized 57 isolates from a 2-phase clonal outbreak of New Delhi metallo-β-lactamase-producing Eschericha coli, involving 9 Israeli hospitals; all but 1 isolate belonged to sequence-type (ST) 410. Most isolates in the second phase harbored blaKPC-2 in addition to blaNDM-5. Genetic sequencing revealed most dual-carbapenemase-producing isolates to be monophyletically derived from a common ancestor.

Published
2021
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