Clinical trial NCT06688084: Pathogenicity Factors of Staphylococcus Pettenkoferi in Foot Wounds and Osteitis in Diabetic Patients
Official title: Evaluation of Pathogenicity Factors of Staphylococcus Pettenkoferi in Foot Wounds and Osteitis in Diabetic Patients
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Diabetic Foot Ulcer
Keywords: Diabetes
Foot
Infection
Staphylococcus pettenkoferi
Osteitis
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
Collaborators: name: Staphylococcal National Reference Center, Lyon, France
name: Rennes University Hospital
name: Nantes University Hospital
name: Universität Tübingen
name: Örebro University, Sweden
name: Charles University, Czech Republic
name: University Hospital Muenster
First posted: 2024-11-14
Enrollment: 230
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The collection of strains at the Nîmes University Hospital site from 9 European laboratories collected between 2015 and 2023 for a total of 108 months was carried out between November 2021 and August 2023.

Brief summary: Gram-positive cocci, particularly Staphylococcus aureus and coagulase-negative staphylococci (SCoN), are the bacteria most frequently isolated from diabetic foot ulcers. Although studies have been carried out on the role of S. aureus in the unfavorable evolution of these wounds, no studies have focused on the role of SCoN. Of the fifty or so SCoN species, not all have the same virulence potential. The role of Staphylococcus pettenkoferi is unknown, yet this bacterium is the 7th most frequently identified in diabetic foot ulcers, suggesting that it may also be involved in the pathophysiology of these infections. At Nîmes University Hospital, this bacterium is mainly identified in samples from diabetic foot ulcers or osteitis in our laboratory and 80% of the bacteria present are in biofilms.It is essential to understand the mechanisms governing these bacterial interactions and establish the true pathogenic potential of these bacteria. Recently, the Nîmes team showed that a strain of S. pettenkoferi (SP165) isolated from foot osteitis in a diabetic patient had real virulence potential. SP165 could not only produce biofilm, but could also survive in human blood, human keratinocytes and murine and human macrophages. It also caused significant embryonic mortality in a zebrafish model. A second study of 29 isolates from Nîmes University Hospital subsequently demonstrated that there were two predominant clones with different virulences. Three biofilm production profiles (rapidly and highly biofilm-producing, slowly biofilm-producing and non-biofilm-producing) and two zebrafish profiles (highly and moderately lethal) were reported by phenotypic and genomic analyses on this panel of strains. Genes for resistance, virulence and biofilm production were also found on their genomes.

Detailed description: Gram-positive cocci, in particular Staphylococcus aureus and coagulase-negative staphylococci (SCoN), are the bacteria most frequently isolated from diabetic foot ulcers. While studies have been carried out on the role of S. aureus in the unfavorable evolution of these wounds, no study has focused on the role of SCoN. Of the fifty or so SCoN species, not all have the same virulence potential. The role of Staphylococcus pettenkoferi is not known. Yet this bacterium is the 7th most frequently identified in diabetic foot ulcers, suggesting that it may also be involved in the pathophysiology of these infections. In the work of Loetsche et al. a study of the microbiome of 349 diabetic foot ulcer samples by targeted 16S rDNA sequencing showed that the genus Staphylococcus was the most abundant, with a relative abundance of 22.8%, including 13.3% S. aureus and 5.3% S. pettenkoferi.

At Nîmes University Hospital, this bacterium is mainly identified in samples from diabetic foot ulcers or osteitis in our laboratory (89 isolations of S. pettenkoferi from diabetic foot ulcer samples out of 167 isolations made of this bacterium between 2018 and 2022).The difficulty of managing chronic wounds also lies in the fact that almost 80% of the bacteria present are in biofilms. It has also been established that the environment in which bacteria are found, and in particular the interactions they establish between themselves, play a significant role in delayed wound healing. It is therefore essential to understand the mechanisms governing these bacterial interactions and to establish the true pathogenic potential of these bacteria.

Recently, our team demonstrated that a strain of S. pettenkoferi (SP165) isolated from foot osteitis in a diabetic patient had real virulence potential. As well as being able to produce biofilm, SP165 was able to survive in human blood, human keratinocytes and murine and human macrophages. It also demonstrated its virulence by causing significant embryonic mortality in the zebrafish model.

A second study of 29 isolates from Nîmes University Hospital subsequently demonstrated the existence of two predominant clones with different virulences.

Three biofilm production profiles (rapidly and highly biofilm-producing, slowly biofilm-producing and non-biofilm-producing) and two zebrafish virulence profiles (highly and moderately lethal) were reported by phenotypic and genomic analyses on this panel of strains. Genes for resistance, virulence and biofilm production were also found on their genomes.

Eligibility criteria: Inclusion Criteria:

* Not applicable for this research on a ready-constituted collection of strains of Staphylococcus pettenkoferi

Exclusion Criteria:

* Not applicable for this research on a ready-constituted collection of strains of Staphylococcus pettenkoferi

Primary outcomes:
measure: Genetic diversity of Staphyloccocus pettenkoferi strains isolated from osteitis and non-diabetic wounds, blood cultures and nasal carriage.
timeFrame: Day 0 to 3 months
Secondary outcomes:
measure: Genetic diversity of Staphyloccocus pettenkoferi strains isolated from osteitis and non-diabetic wounds, blood cultures and nasal carriage.
timeFrame: 3 - 6 months
measure: Resistome in the strain population according to sample origin:osteitis
timeFrame: 3 - 6 months
measure: Resistome in the strain population according to sample origin: non-diabetic wounds
timeFrame: 3 - 6 months
measure: Resistome in the strain population according to sample origin: diabetic wounds
timeFrame: 3 - 6 months
measure: Resistome in the strain population according to sample origin: blood cultures
timeFrame: 3 - 6 months
measure: Resistome in the strain population according to sample origin: nasal carriage
timeFrame: 3 - 6 months
measure: Virulome in the strain population according to sample origin: osteitis
timeFrame: 3 - 6 months
measure: Virulome in the strain population according to sample origin: non-diabetic wounds
timeFrame: 3 - 6 months
measure: Virulome in the strain population according to sample origin: diabetic wounds
timeFrame: 3 - 6 months
measure: Virulome in the strain population according to sample origin: blood cultures
timeFrame: 3 - 6 months
measure: Virulome in the strain population according to sample origin: nasal carriage
timeFrame: 3 - 6 months
measure: Plasmids inthe strain population and according to sample origin: osteitis
timeFrame: 3 - 6 months
measure: Plasmids inthe strain population and according to sample origin: non-diabetic wounds
timeFrame: 3 - 6 months
measure: Plasmids inthe strain population and according to sample origin: diabetic wounds
timeFrame: 3 - 6 months
measure: Plasmids inthe strain population and according to sample origin: blood cultures
timeFrame: 3 - 6 months
measure: Plasmids inthe strain population and according to sample origin: nasal carriage
timeFrame: 3 - 6 months
measure: Phenotypic resistance profiles in the population in a subsample of 85 strains
timeFrame: 6 - 14 months
measure: Phenotypic resistance profiles in the population and according to sample origin: osteitis
timeFrame: 6 - 14 months
measure: Phenotypic resistance profiles in the population and according to sample origin: non-diabetic wounds
timeFrame: 6 - 14 months
measure: Phenotypic resistance profiles in the population and according to sample origin: diabetic wounds
timeFrame: 6 - 14 months
measure: Phenotypic resistance profiles in the population and according to sample origin: blood cultures
timeFrame: 6 - 14 months
measure: Phenotypic resistance profiles in the population and according to sample origin: nasal carriage
timeFrame: 6 - 14 months
measure: Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: osteitis
timeFrame: 6 - 14 months
measure: Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: non-diabetic wounds
timeFrame: 6 - 14 months
measure: Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: diabetic wounds
timeFrame: 6 - 14 months
measure: Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: blood cultures
timeFrame: 6 - 14 months
measure: Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: nasal carriage
timeFrame: 6 - 14 months
measure: Bacterial growth rate according to sample origin in a sub-sample of 20 strains: osteitis
timeFrame: 6 - 14 months
measure: Bacterial growth rate according to sample origin in a sub-sample of 20 strains: non-diabetic wounds
timeFrame: 6 - 14 months
measure: Bacterial growth rate according to sample origin in a sub-sample of 20 strains: diabetic wounds
timeFrame: 6 - 14 months
measure: Bacterial growth rate according to sample origin in a sub-sample of 20 strains: blood cultures
timeFrame: 6 - 14 months
measure: Bacterial growth rate according to sample origin in a sub-sample of 20 strains: nasal carriage
timeFrame: 6 - 14 months
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: osteitis
timeFrame: 6 - 14 months
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: intracellular bacterial multiplication of S. pettenkoferi strains from osteitis
timeFrame: 6 - 14 months
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: diabetic wounds
timeFrame: 6 - 14 months
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: intracellular bacterial multiplication of S. pettenkoferi strains from diabetic wounds
timeFrame: 6 - 14 months
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: blood cultures
timeFrame: 6 - 14 months
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains:intracellular bacterial multiplication of S. pettenkoferi strains from blood cultures
timeFrame: 6 - 14 months
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: nasal carriage
timeFrame: 6 - 14 months
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains:intracellular bacterial multiplication of S. pettenkoferi strains from nasal carriage
timeFrame: 6 - 14 months
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from osteitis
timeFrame: Up to 48 hours
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from non-diabetic wounds
timeFrame: Up to 48 hours
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from diabetic wounds
timeFrame: Up to 48 hours
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from blood cultures
timeFrame: Up to 48 hours
measure: Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from nasal carriage
timeFrame: Up to 48 hours
Other outcomes:
Locations:
city: Nîmes
country: France
facility: Nîmes University Hospital
state: Gard
Study officials:
affiliation: Nîmes University Hospital, FRANCE
name: Chloé MAGNAN, Dr.
role: PRINCIPAL_INVESTIGATOR
References: