Genomics of Staphylococcus aureus and Staphylococcus epidermidis from Periprosthetic Joint Infections and Correlation to Clinical Outcome

Margarita Trobos; Rininta Firdaus; Karin Svensson Malchau; Jonatan Tillander; Dimitrios  Arnellos; Ola  Rolfson; Peter Thomsen; Inigo Lasa

doi:10.1128/spectrum.02181-21

Genomics of Staphylococcus aureus and Staphylococcus epidermidis from Periprosthetic Joint Infections and Correlation to Clinical Outcome

Margarita Trobos^*, Rininta Firdaus, Karin Svensson Malchau, Jonatan Tillander, Dimitrios Arnellos, Ola Rolfson, Peter Thomsen, Inigo Lasa^*

^*Corresponding author for this work

Dentistry

Research output: Contribution to journal › Article › peer-review

18 Downloads (Pure)

Abstract

The approach of sequencing or genotyping to characterize the pathogenic potential of staphylococci from orthopedic device-related infection (ODRI) has been applied in recent studies. These studies described the genomic carriage of virulence in clinical strains and compared it with those in commensal strains. Only a few studies have directly correlated genomic profiles to patient outcome and phenotypic virulence properties in periprosthetic joint infections (PJIs). We investigated the association between genomic variations and virulence-associated phenotypes (biofilm-forming ability and antimicrobial resistance) in 111 staphylococcal strains isolated from patients with PJI and the infection outcome (resolved/unresolved). The presence of a strong biofilm phenotype in Staphylococcus aureus and an antibiotic-resistant phenotype in Staphylococcus epidermidis were both associated with treatment failure of PJI. In S. epidermidis, multidrug resistance (MDR) and resistance to rifampicin were associated with unresolved infection. Sequence type 45 (ST45) and ST2 were particularly enriched in S. aureus and S. epidermidis, respectively. S. epidermidis ST2 caused the majority of relapses and was associated with MDR and strong biofilm production, whereas ST215 correlated with MDR and non/weak biofilm production. S. aureus agr II correlated with resolved infection, while S. epidermidis agr I was associated with strong biofilm production and agr III with non/weak production. Collectively, our results highlight the importance of careful genomic and phenotypic characterization to anticipate the probability of the strain causing treatment failure in PJI. Due to the high rate of resistant S. epidermidis strains identified, this study provides evidence that the current recommended treatment of rifampicin and a fluoroquinolone should not be administered without knowledge of the resistance pattern.

Original language	English
Article number	e02181-21
Number of pages	20
Journal	Microbiology spectrum
Volume	10
Issue number	4
Early online date	28 Jun 2022
DOIs	https://doi.org/10.1128/spectrum.02181-21
Publication status	Published - Aug 2022

Bibliographical note

Funding:
This work was sponsored by the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754412 (MoRE2020 - Region Västra Götaland), Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg, Swedish Research Council (2018-02891; 2020-05703), the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG-725641; ALFGBG-719961), the IngaBritt and Arne Lundberg Foundation (LU2021-0048), the Hjalmar Svensson Foundation, the Doctor Felix Neuberghs Foundation, the Adlerbertska Foundation, the Sylvan Foundation, Göteborgs Läkaresällskap/The Gothenburg Medical Society research grants (for PhD studies and Svea Bäcksins grant GLS-780551), the Area of Advance Materials of Chalmers/GU Biomaterials within the Strategic Research Area initiative launched by the Swedish government, and the Spanish Ministry of Science, Innovation and Universities grant (PID2020-113494RB-I00) (Agencia Española de Investigación/Fondo Europeo de Desarrollo Regional, European Union).

Keywords

Staphylococcus
periprosthetic joint infection
biofilm
antibiotic resistance
virulence
patient outcome
whole-genome sequencing

Access to Document

10.1128/spectrum.02181-21Licence: Creative Commons: Attribution (CC BY)

TrobosM2022GenomicsFinal published version, 2.34 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

@article{f29b026692d344beb1b05040d6abbeaa,

title = "Genomics of Staphylococcus aureus and Staphylococcus epidermidis from Periprosthetic Joint Infections and Correlation to Clinical Outcome",

abstract = "The approach of sequencing or genotyping to characterize the pathogenic potential of staphylococci from orthopedic device-related infection (ODRI) has been applied in recent studies. These studies described the genomic carriage of virulence in clinical strains and compared it with those in commensal strains. Only a few studies have directly correlated genomic profiles to patient outcome and phenotypic virulence properties in periprosthetic joint infections (PJIs). We investigated the association between genomic variations and virulence-associated phenotypes (biofilm-forming ability and antimicrobial resistance) in 111 staphylococcal strains isolated from patients with PJI and the infection outcome (resolved/unresolved). The presence of a strong biofilm phenotype in Staphylococcus aureus and an antibiotic-resistant phenotype in Staphylococcus epidermidis were both associated with treatment failure of PJI. In S. epidermidis, multidrug resistance (MDR) and resistance to rifampicin were associated with unresolved infection. Sequence type 45 (ST45) and ST2 were particularly enriched in S. aureus and S. epidermidis, respectively. S. epidermidis ST2 caused the majority of relapses and was associated with MDR and strong biofilm production, whereas ST215 correlated with MDR and non/weak biofilm production. S. aureus agr II correlated with resolved infection, while S. epidermidis agr I was associated with strong biofilm production and agr III with non/weak production. Collectively, our results highlight the importance of careful genomic and phenotypic characterization to anticipate the probability of the strain causing treatment failure in PJI. Due to the high rate of resistant S. epidermidis strains identified, this study provides evidence that the current recommended treatment of rifampicin and a fluoroquinolone should not be administered without knowledge of the resistance pattern.",

keywords = "Staphylococcus, periprosthetic joint infection, biofilm, antibiotic resistance, virulence, patient outcome, whole-genome sequencing",

author = "Margarita Trobos and Rininta Firdaus and Malchau, {Karin Svensson} and Jonatan Tillander and Dimitrios Arnellos and Ola Rolfson and Peter Thomsen and Inigo Lasa",

note = "Funding: This work was sponsored by the European Union Horizon 2020 research and innovation program under the Marie Sk{\l}odowska-Curie grant agreement no. 754412 (MoRE2020 - Region V{\"a}stra G{\"o}taland), Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg, Swedish Research Council (2018-02891; 2020-05703), the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG-725641; ALFGBG-719961), the IngaBritt and Arne Lundberg Foundation (LU2021-0048), the Hjalmar Svensson Foundation, the Doctor Felix Neuberghs Foundation, the Adlerbertska Foundation, the Sylvan Foundation, G{\"o}teborgs L{\"a}kares{\"a}llskap/The Gothenburg Medical Society research grants (for PhD studies and Svea B{\"a}cksins grant GLS-780551), the Area of Advance Materials of Chalmers/GU Biomaterials within the Strategic Research Area initiative launched by the Swedish government, and the Spanish Ministry of Science, Innovation and Universities grant (PID2020-113494RB-I00) (Agencia Espa{\~n}ola de Investigaci{\'o}n/Fondo Europeo de Desarrollo Regional, European Union).",

year = "2022",

month = aug,

doi = "10.1128/spectrum.02181-21",

language = "English",

volume = "10",

journal = "Microbiology spectrum",

issn = "2165-0497",

publisher = "American Society for Microbiology",

number = "4",

}

TY - JOUR

T1 - Genomics of Staphylococcus aureus and Staphylococcus epidermidis from Periprosthetic Joint Infections and Correlation to Clinical Outcome

AU - Trobos, Margarita

AU - Firdaus, Rininta

AU - Malchau, Karin Svensson

AU - Tillander, Jonatan

AU - Arnellos, Dimitrios

AU - Rolfson, Ola

AU - Thomsen, Peter

AU - Lasa, Inigo

N1 - Funding: This work was sponsored by the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754412 (MoRE2020 - Region Västra Götaland), Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg, Swedish Research Council (2018-02891; 2020-05703), the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG-725641; ALFGBG-719961), the IngaBritt and Arne Lundberg Foundation (LU2021-0048), the Hjalmar Svensson Foundation, the Doctor Felix Neuberghs Foundation, the Adlerbertska Foundation, the Sylvan Foundation, Göteborgs Läkaresällskap/The Gothenburg Medical Society research grants (for PhD studies and Svea Bäcksins grant GLS-780551), the Area of Advance Materials of Chalmers/GU Biomaterials within the Strategic Research Area initiative launched by the Swedish government, and the Spanish Ministry of Science, Innovation and Universities grant (PID2020-113494RB-I00) (Agencia Española de Investigación/Fondo Europeo de Desarrollo Regional, European Union).

PY - 2022/8

Y1 - 2022/8

N2 - The approach of sequencing or genotyping to characterize the pathogenic potential of staphylococci from orthopedic device-related infection (ODRI) has been applied in recent studies. These studies described the genomic carriage of virulence in clinical strains and compared it with those in commensal strains. Only a few studies have directly correlated genomic profiles to patient outcome and phenotypic virulence properties in periprosthetic joint infections (PJIs). We investigated the association between genomic variations and virulence-associated phenotypes (biofilm-forming ability and antimicrobial resistance) in 111 staphylococcal strains isolated from patients with PJI and the infection outcome (resolved/unresolved). The presence of a strong biofilm phenotype in Staphylococcus aureus and an antibiotic-resistant phenotype in Staphylococcus epidermidis were both associated with treatment failure of PJI. In S. epidermidis, multidrug resistance (MDR) and resistance to rifampicin were associated with unresolved infection. Sequence type 45 (ST45) and ST2 were particularly enriched in S. aureus and S. epidermidis, respectively. S. epidermidis ST2 caused the majority of relapses and was associated with MDR and strong biofilm production, whereas ST215 correlated with MDR and non/weak biofilm production. S. aureus agr II correlated with resolved infection, while S. epidermidis agr I was associated with strong biofilm production and agr III with non/weak production. Collectively, our results highlight the importance of careful genomic and phenotypic characterization to anticipate the probability of the strain causing treatment failure in PJI. Due to the high rate of resistant S. epidermidis strains identified, this study provides evidence that the current recommended treatment of rifampicin and a fluoroquinolone should not be administered without knowledge of the resistance pattern.

AB - The approach of sequencing or genotyping to characterize the pathogenic potential of staphylococci from orthopedic device-related infection (ODRI) has been applied in recent studies. These studies described the genomic carriage of virulence in clinical strains and compared it with those in commensal strains. Only a few studies have directly correlated genomic profiles to patient outcome and phenotypic virulence properties in periprosthetic joint infections (PJIs). We investigated the association between genomic variations and virulence-associated phenotypes (biofilm-forming ability and antimicrobial resistance) in 111 staphylococcal strains isolated from patients with PJI and the infection outcome (resolved/unresolved). The presence of a strong biofilm phenotype in Staphylococcus aureus and an antibiotic-resistant phenotype in Staphylococcus epidermidis were both associated with treatment failure of PJI. In S. epidermidis, multidrug resistance (MDR) and resistance to rifampicin were associated with unresolved infection. Sequence type 45 (ST45) and ST2 were particularly enriched in S. aureus and S. epidermidis, respectively. S. epidermidis ST2 caused the majority of relapses and was associated with MDR and strong biofilm production, whereas ST215 correlated with MDR and non/weak biofilm production. S. aureus agr II correlated with resolved infection, while S. epidermidis agr I was associated with strong biofilm production and agr III with non/weak production. Collectively, our results highlight the importance of careful genomic and phenotypic characterization to anticipate the probability of the strain causing treatment failure in PJI. Due to the high rate of resistant S. epidermidis strains identified, this study provides evidence that the current recommended treatment of rifampicin and a fluoroquinolone should not be administered without knowledge of the resistance pattern.

KW - Staphylococcus

KW - periprosthetic joint infection

KW - biofilm

KW - antibiotic resistance

KW - virulence

KW - patient outcome

KW - whole-genome sequencing

U2 - 10.1128/spectrum.02181-21

DO - 10.1128/spectrum.02181-21

M3 - Article

SN - 2165-0497

VL - 10

JO - Microbiology spectrum

JF - Microbiology spectrum

IS - 4

M1 - e02181-21

ER -

Genomics of Staphylococcus aureus and Staphylococcus epidermidis from Periprosthetic Joint Infections and Correlation to Clinical Outcome

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this