Strong Biofilm Formation and Low Cloxacillin Susceptibility in Biofilm-Growing CC398 Staphylococcus aureus Responsible for Bacteremia in French Intensive Care Units, 2021

Nathalie van der Mee-Marquet; Sandra Dos Santos; Seydina M Diene; Isabelle Duflot; Laurent Mereghetti; Anne-Sophie Valentin; Patrice François; On Behalf Of The Spiadi Collaborative Group

doi:10.3390/microorganisms10091857

Strong Biofilm Formation and Low Cloxacillin Susceptibility in Biofilm-Growing CC398 Staphylococcus aureus Responsible for Bacteremia in French Intensive Care Units, 2021

Microorganisms. 2022 Sep 16;10(9):1857. doi: 10.3390/microorganisms10091857.

Authors

Nathalie van der Mee-Marquet¹, Sandra Dos Santos¹, Seydina M Diene², Isabelle Duflot¹, Laurent Mereghetti³, Anne-Sophie Valentin¹, Patrice François⁴, On Behalf Of The Spiadi Collaborative Group

Affiliations

¹ Centre d'Appui pour la Prévention des Infections Associées aux Soins (CPias) de la Région Centre Val de Loire, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire, 37044 Tours, France.
² Faculté de Pharmacie, Microbes Evolution Phylogeny and Infections, IHU-Méditerranée Infection, Aix-Marseille Université, 13005 Marseille, France.
³ Service de Bactériologie, Virologie et Hygiène, Hôpital Trousseau, Centre Hospitalier Régional Universitaire, 37044 Tours, France.
⁴ Department of Medicine, University of Geneva Hospitals, 1205 Geneva, Switzerland.

Abstract

A prospective 3-month study carried out in 267 ICUs revealed an S. aureus nosocomial bacteremia in one admitted patient out of 110 in adult and pediatric sectors, and in one out of 230 newborns; 242 S. aureus bacteremias occurred during the study, including 7.9% MRSA-bacteremias. In one ICU out of ten, the molecular characteristics, antimicrobial susceptibility profiles and biofilm production of the strains responsible for S. aureus bacteremia were studied. Of the 53 strains studied, 9.4% were MRSA and 52.8% were resistant to erythromycin. MLST showed the predominance of CC398 (37.7% of the strains) followed by CC8 (17.0%), CC45 (13.2%) and CC30 (9.4%). The lukF/S genes were absent from our isolates and tst-1 was found in 9.4% of the strains. Under static conditions and without exposure to glucose, biofilm production was rare (9.4% of the strains, without any CC398). The percentage increased to 62.3% for strains grown in broth supplemented with 1% glucose (including 7 out of 9 CC8 and 17 out of the 20 CC398). Further study of the CC398, including whole genome sequencing, revealed (1) highly frequent patient death within seven days after CC398 bacteremia diagnosis (47.4%), (2) 95.0% of the strains producing biofilm when exposed to sub-inhibitory concentrations of cloxacillin, (3) a stronger biofilm production following exposure to cloxacillin than that observed in broth supplemented with glucose only (p < 0.001), (4) a high minimum biofilm eradication concentration of cloxacillin (128 mg/L) indicating a low cloxacillin susceptibility of biofilm-growing CC398, (5) 95.0% of the strains carrying a ϕSa-3 like prophage and its particular evasion cluster (i.e., yielding chp and scin genes), and (6) 30.0% of the strains carrying a ϕMR11-like prophage and yielding a higher ability to produce biofilm. Our results provide evidence that active surveillance is required to avoid spreading of this virulent staphylococcal clone.

Keywords: CC398; Staphylococcus aureus; antibiotic tolerance; bacteremia; biofilm; cloxacillin; intensive care.

Grants and funding

This work was supported by subside from the Swiss National Science Foundation (to P.F.) Project 310030_197734.