Molecular Characteristics of Colistin Resistance in Acinetobacter baumannii and the Activity of Antimicrobial Combination Therapy in a Tertiary Care Medical Center in Lebanon

Author:

Abou Fayad Antoine123ORCID,Haraoui Louis-Patrick45,Sleiman Ahmad123,Hussein Hadi123,Grenier Frédéric6,Derbaj Ghada123,Itani Dana123,Iweir Sereen123,Sherri Nour123,Bazzi Wael123,Rasheed Sari123,Tanelian Arax123,Miari Mariam123,el Hafi Bassam123ORCID,Kanj Souha S.27ORCID,Kanafani Zeina A.27,Daoud Ziad8ORCID,Araj George F.29,Matar Ghassan M.123

Affiliation:

1. Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon

2. Center for Infectious Diseases Research, American University of Beirut, Beirut 1107 2020, Lebanon

3. World Health Organization (WHO) Collaborating Center for Reference and Research on Bacterial Pathogens, Beirut 1107 2020, Lebanon

4. Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada

5. Centre de recherche Charles-Le Moyne, Hôpital Charles-Le Moyne, Greenfield Park, QC J4V 2G9, Canada

6. Department of Biology, Faculty of Science, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada

7. Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon

8. Laboratory Department, My Michigan Health Midland Medical Center, College of Medicine, Central Michigan University, Saginaw, MI 48602, USA

9. Department of Pathology and Laboratory Medicine, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon

Abstract

(1) Background: Infections with pan-drug-resistant (PDR) bacteria, such as A. baumannii, are becoming increasingly common, especially in healthcare facilities. In this study, we selected 15 colistin-resistant clinical A. baumannii isolates from a hospital in Beirut, Lebanon, to test combination therapies and determine their sequence types (STs) and the mechanism of colistin resistance using whole-genome sequencing (WGS). (2) Methods: Antimicrobial susceptibility testing via broth microdilution against 12 antimicrobials from different classes and growth rate assays were performed. A checkerboard assay was conducted on PDR isolates using six different antimicrobials, each in combination with colistin. Genomic DNA was extracted from all isolates and subjected to WGS. (3) Results: All isolates were resistant to all tested antimicrobials with the one exception that was susceptible to gentamicin. Combining colistin with either meropenem, ceftolozane–tazobactam, or teicoplanin showed synergistic activity. Sequencing data revealed that 67% of the isolates belonged to Pasteur ST2 and 33% to ST187. Furthermore, these isolates harbored a number of resistance genes, including blaOXA-23. Mutations in the pmrC gene were behind colistin resistance. (4) Conclusions: With the rise in antimicrobial resistance and the absence of novel antimicrobial production, alternative treatments must be found. The combination therapy results from this study suggest treatment options for PDR ST2 A. baumannii-infected patients.

Funder

American University of Beirut Medical Practice Plan, MPP

Publisher

MDPI AG

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