Multidrug-resistant Enterobacterales responsible for septicaemia in a neonatal intensive care unit in Morocco

Patricia Perez-Palacios; Delphine Girlich; Nabila Soraa; Asmae Lamrani; Fadl Mrabih Rabo Maoulainine; Fatiha Bennaoui; Hasna Amri; Nadia Slitine El Idrissi; Mohammed Bouskraoui; Aurélien Birer; Agnes B Jousset; Saoussen Oueslati; Josette Raymond; Thierry Naas

doi:10.1016/j.jgar.2023.02.011

Multidrug-resistant Enterobacterales responsible for septicaemia in a neonatal intensive care unit in Morocco

J Glob Antimicrob Resist. 2023 Jun:33:208-217. doi: 10.1016/j.jgar.2023.02.011. Epub 2023 Mar 2.

Authors

Affiliations

¹ Microbiology and Infectious Diseases Unit, University Hospital Virgen Macarena, Sevilla, Spain; Team ReSIST, INSERM U1184, LabEx LERMIT, School of Medicine, University Paris-Saclay, AP-HP Paris-Saclay.
² Team ReSIST, INSERM U1184, LabEx LERMIT, School of Medicine, University Paris-Saclay, AP-HP Paris-Saclay; French National Reference Center for Antibiotic Resistance: Carbapenemase-producing Enterobacterales, Hopital Bicêtre, AP-HP Paris-Saclay, Le Kremlin-Bicêtre, France.
³ Service de Microbiologie, CHU Mohammed VI Marrakech, Morocco.
⁴ Service de réanimation néonatale CHU Mohammed VI Marrakech, Morocco.
⁵ Service de Pédiatrie CHU Mohammed VI Marrakech, Morocco.
⁶ French National Reference Center for Antibiotic Resistance: Carbapenemase-producing Enterobacterales, Hopital Bicêtre, AP-HP Paris-Saclay, Le Kremlin-Bicêtre, France.
⁷ Team ReSIST, INSERM U1184, LabEx LERMIT, School of Medicine, University Paris-Saclay, AP-HP Paris-Saclay.
⁸ Team ReSIST, INSERM U1184, LabEx LERMIT, School of Medicine, University Paris-Saclay, AP-HP Paris-Saclay. Electronic address: josette.raymond1@gmail.com.
⁹ Team ReSIST, INSERM U1184, LabEx LERMIT, School of Medicine, University Paris-Saclay, AP-HP Paris-Saclay; French National Reference Center for Antibiotic Resistance: Carbapenemase-producing Enterobacterales, Hopital Bicêtre, AP-HP Paris-Saclay, Le Kremlin-Bicêtre, France. Electronic address: thierry.naas@aphp.fr.

PMID: 36868310
DOI: 10.1016/j.jgar.2023.02.011

Abstract

Objectives: Neonatal sepsis caused by multidrug-resistant (MDR) bacteria has a high morbidity and mortality, especially in low- and middle-income countries. Here, the molecular mechanisms of multidrug resistance in bacteria responsible for neonatal sepsis were determined.

Methods: From July to December 2019, documented bacteraemia from 524 neonates hospitalised in a neonatal intensive care unit in Morocco were collected. Whole-genome sequencing was used to characterise the resistome; multi-locus sequence typing was used to investigate phylogeny.

Results: Among the 199 cases of documented bacteraemia, 40 (20%) and 20 (10%) were caused by MDR Klebsiella pneumoniae and Enterobacter hormaechei, respectively. Of these, 23 (38.5%) were early neonatal infections (≤3 days of life). Twelve different sequence types (STs) were observed among K. pneumoniae isolates, the most prevalent being ST1805 (n = 10) and ST307 (n = 8). Twenty-one K. pneumoniae isolates (53%) possessed the bla_CTX-M-15 gene, six of which co-produced OXA-48; two, NDM-7; and two, OXA-48 and NDM-7. The bla_OXA-48 gene was present in 11 K. pneumoniae isolates (27.5%); bla_NDM-1, in 13 (32.5%); and bla_NDM-7, in 4 (10.0%). Eighteen E. hormaechei isolates (90.0%) produced an extended-spectrum β-lactamase (ESBL). Three were SHV-12 producers that co-produced CMY-4 and NDM-1, and 15 were CTXM-15 producers, of which 6 co-produced OXA-48. Twelve different STs belonging to three different E. hormaechei subspecies were observed, with one to four isolates. K. pneumoniae and E. hormaechei isolates belonging to the same ST had less than 20 single nucleotide polymorphism differences and were found throughout the study period, highlighting their endemic presence in the neonatal intensive care unit.

Conclusion: Thirty percent of neonatal sepsis cases (23 early and 37 late) were caused by highly drug-resistant carbapenemase- and/or ESBL-producing Enterobacterales.

Keywords: Carbapenemase-producing Enterobacterales; Extended-spectrum β-lactamases; Morocco; Neonatal intensive care unit; Outbreak; Sepsis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Bacteremia* / drug therapy
Bacteremia* / epidemiology
Humans
Infant, Newborn
Intensive Care Units, Neonatal
Klebsiella Infections* / microbiology
Klebsiella pneumoniae / genetics
Morocco / epidemiology
Multilocus Sequence Typing
Neonatal Sepsis* / drug therapy
Neonatal Sepsis* / epidemiology
Sepsis* / drug therapy
beta-Lactamases / genetics

Substances

Anti-Bacterial Agents
beta-Lactamases