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

Author:

Frenk Sammy1,Temkin Elizabeth1,Lurie-Weinberger Mor N.1,Keren-Paz Alona1,Rov Reut1,Rakovitsky Nadya1,Wullfhart Liat1,Nutman Amir123ORCID,Daikos George L.45,Skiada Anna45ORCID,Durante-Mangoni Emanuele67,Dishon Benattar Yael89,Bitterman Roni8,Yahav Dafna310,Daitch Vered311,Bernardo Mariano67,Iossa Domenico67,Zusman Oren11,Friberg Lena E.12ORCID,Mouton Johan W.13,Theuretzbacher Ursula14ORCID,Leibovici Leonard311,Geffen Yuval15,Gershon Rina15,Paul Mical816,Carmeli Yehuda123

Affiliation:

1. National Institute for Antibiotic Resistance and Infection Control, Israel Ministry of Health, Tel Aviv, Israel

2. Division of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

4. First Department of Medicine, Laikon General Hospital, Athens, Greece

5. National and Kapodistrian University of Athens, Athens, Greece

6. Department of Precision Medicine, University of Campania Luigi Vanvitelli, Napoli, Italy

7. AORN dei Colli-Monaldi Hospital, Napoli, Italy

8. Institute of Infectious Diseases, Rambam Health Care Campus, Haifa, Israel

9. The Cheryl Spencer Institute for Nursing Research, University of Haifa, Haifa, Israel

10. Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel

11. Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel

12. Department of Pharmacy, Uppsala University, Uppsala, Sweden

13. Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands

14. Center for Anti-Infective Agents, Vienna, Austria

15. Microbiology Laboratory, Rambam Health Care Campus, Haifa, Israel

16. The Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

Abstract

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.

Funder

EU AIDA

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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