Neonatal sepsis due to NDM-1 and VIM-2 co-producing Pseudomonas aeruginosa in Morocco

Author:

Daaboul Dina12,Osman Marwan3,Kassem Issmat I4ORCID,Yassine Iman2,Girlich Delphine1,Proust Alexis5,Mounir Chemsi6,Zerouali Khalid7,Raymond Josette8,Naas Thierry189ORCID,Oueslati Saoussen18

Affiliation:

1. Team ReSIST, UMR1184, INSERM, Université Paris-Saclay, CEA, School of Medicine, OI HEALTHI , Le Kremlin-Bicêtre , France

2. Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University , Tripoli 1300 , Lebanon

3. Department of Neurosurgery, Yale University School of Medicine , New Haven, CT 06510 , USA

4. Center for Food Safety and Department of Food Science and Technology, University of Georgia , 1109 Experiment Street, Griffin, GA 30223-1797 , USA

5. Department of Hormonal Biochemistry, Hôpital de Bicêtre, Assistance Publique—Hôpitaux de Paris , Le Kremlin-Bicêtre , France

6. Service de néonatalogie, CHU Ibn Rochd, Faculté de Médecine et de Pharmacie de Casablanca, Université Hassan II , Casablanca , Morocco

7. Service de Microbiologie, CHU Ibn Rochd, Faculté de Médecine et de Pharmacie de Casablanca, Université Hassan II , Casablanca , Morocco

8. Bacteriology-Hygiene Unit, Bicêtre Hospital, APHP Paris-Saclay , Le Kremlin-Bicêtre 94270 , France

9. French National Reference Center for Antibiotic Resistance: Carbapenemase-producing Enterobacterales , Le Kremlin-Bicêtre , France

Abstract

Abstract Background Carbapenem-resistant Pseudomonas aeruginosa are being increasingly described worldwide. Here, we investigated the molecular mechanisms underlying carbapenem resistance in an extremely drug-resistant P. aeruginosa isolate from a neonatal intensive care unit in Morocco. Materials and methods P. aeruginosa strain O82J1 was identified using MALDI-TOF-MS. Carba NP, immunochromatographic assay NG Carba5 and antimicrobial susceptibility testing using disc diffusion and microbroth were performed. Whole-genome sequencing using the Illumina and MinION technologies and different software packages available at the Center of Genomic Epidemiology were used to predict the resistome, sequence type and plasmid types. Results P. aeruginosa O82J1 co-expressed two metallo-β-lactamases, blaNDM-1 and blaVIM-2, and was susceptible to colistin and apramycin only. It belonged to ST773 that is frequently reported worldwide as a high-risk P. aeruginosa clone. The blaVIM-2 gene was integron-borne on a IncP-2 465-kb plasmid, whereas the blaNDM-1 gene was chromosomally encoded and embedded in an integrative conjugative element, probably at the origin of its acquisition. A total of 23 antimicrobial resistance genes were detected including a blaPER-1 ESBL gene, and an 16S-rRNA methyltransferase gene rmtB. Conclusions The isolation of XDR P. aeruginosa isolates expressing several carbapenemases in a neonatal intensive care unit is of great concern due to the reduced treatment options, relying only on colistin, but not recommended in neonates, and apramycin, not yet approved for human therapy. Concerns were further elevated due to the resistance to cefiderocol and ATM/AVI, two novel and last-resort antibiotics recommended to treat infections caused by Gram-negative bacteria, particularly XDR P. aeruginosa in adults.

Funder

Assistance Publique-Hôpitaux de Paris

Institut National de la Santé et de la Recherche Médicale

French National Research Agency

SAFAR Doctoral Scholarship

Lebanese University

Publisher

Oxford University Press (OUP)

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