Diabetes and necrotizing soft tissue infections—A prospective observational cohort study: Statistical analysis plan

Rosén, Anders; Arnell, Per; Madsen, Martin Bruun; Nedrebø, Bjørn Gunnar; Norrby‐Teglund, Anna; Hyldegaard, Ole; Bergey, François; Saccenti, Edoardo; Skrede, Steinar

doi:10.1111/aas.13130

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…People with diabetes have more severe and frequent bacterial infections and a higher mortality rate than people without diabetes. Studies have shown that skin and soft tissue infection was more common in patients with diabetes, followed by urinary infections 35 . Co‐infection was much more common in patients with diabetes, and the infection involved more sites.…”

Section: Discussionmentioning

confidence: 99%

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Association of sarcopenia with a higher risk of infection in patients with type 2 diabetes

Zhang

Weng

Huang

et al. 2021

Diabetes Metabolism Res

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Aims: This study aimed to determine whether patients with type 2 diabetes and sarcopenia had a higher risk of infection. Study designs:A cross-sectional study and a follow-up study were performed.Method: A total of 2562 patients were enrolled and assessed for body composition and infection status. They were classified into four groups according to body fat (BF) and muscle mass index (ASMI): obese, sarcopenic, sarcopenic obese, and normal. Among these, 275 patients were followed for a median follow-up period of 1.84 years to evaluate the relationship of changes in skeletal muscle with infection status. Results:The sarcopenic and sarcopenic obese groups showed a higher risk of infection, an increase by 49.6% (OR = 1.496, 95% CI 1.102-2.031) and 42.4% (OR = 1.424, 95% CI 1.031-1.967) compared with the normal group, and also had a higher risk of respiratory infection, an increase by 56.0% (OR = 1.560, 95% CI 1.084-2.246) and 57.4% (OR = 1.574, 95% CI 1.080-2.293), respectively. Patients with the increased ASMI (OR = 0.079, 95% CI 0.021-0.298) represented a lower risk of infection than those with the decreased ASMI. Even a minor change (OR = 0.125, 95% CI 0.041-0.378) against age was beneficial to lowering the risk of infection. However, no association was found in the changes of body mass index and BF with infection status.Conclusions: Sarcopenia, especially in patients with diabetes who are also obese, increases the risk of infection. Maintaining or improving muscle mass is expected to reduce infections.

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Section: Discussionmentioning

confidence: 99%

“…Studies have shown that skin and soft tissue infection was more common in patients with diabetes, followed by urinary infections. 35 Co-infection was much more common in patients with diabetes, and the infection involved more sites. Consequently, the rate of admission due to infection was also higher.…”

Section: Discussionmentioning

confidence: 99%

Association of sarcopenia with a higher risk of infection in patients with type 2 diabetes

Zhang

Weng

Huang

et al. 2021

Diabetes Metabolism Res

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“…The diagnosis of NSTI was made by the surgeon during the primary operation. It is based on, but not restricted to, findings of necrosis, dissolved or deliquescent soft tissue, and fascial and muscular affection (22). The invasive non-NSTI SA control strains consisted in Bloodstream infection (BSI) strains (12 infective endocarditis, 9 bacteremia without infective endocarditis) collected during a prospective cohort study on S. aureus bacteremia (VIRSTA) (23).…”

Section: Methodsmentioning

confidence: 99%

Necrotizing Soft Tissue Infections Staphylococcus aureus - but not Streptococcus pyogenes-isolates display high rate of internalization and cytotoxicity toward human myoblasts

Baude

Bastien

Gillet

et al. 2019

Preprint

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Necrotizing Soft Tissue Infections (NSTIs), often reaching the deep fascia and muscle, are mainly caused by group A Streptococcus (GAS) and to a lesser extent by Staphylococcus aureus (SA). Conversely SA is a leading etiologic agent of pyomyositis suggesting that SA could have a specific tropism for the muscle. To assess the pathogenicity of these two bacterial species for muscles cells in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA were assessed on these cells. Bloodstream infections (BSI) SA isolates and non-invasive coagulase negative Staphylococci (CNS) isolates were used as controls.SA isolates from NSTI and from BSI exhibited stronger internalization into human keratinocytes and myoblasts than CNS or NSTI-GAS. While the median level of SA internalization culminated at 2% in human keratinocytes, it reached over 30% in human myoblasts due to a higher percentage of infected myoblasts (>11%) as compared to keratinocytes (<3%) assessed by transmission electron microscopy. Higher cytotoxicity for myoblasts of NSTI-SA as compared to BSI-SA, was attributed to higher levels of psmα and RNAIII transcripts in NSTI group as compared to hematogenous group. However, the two groups were not discriminated at the genomic level. The cellular basis of high internalization rate in myoblasts was attributed to higher expression of α5β1 integrin in myoblasts as compared to keratinocytes. Major contribution of FnbpAB-integrin α5β1 pathway to internalization was confirmed by isogenic mutants.Our findings suggest the contribution of NSTI-SA severity by its unique propensity to invade and kill myoblasts, a property not shared by NSTI-GAS.ImportanceNecrotizing Soft Tissue Infection (NSTI) is a severe infection caused mainly by group A Streptococcus (GAS) and occasionally by S. aureus (SA); the latter being more often associated with pyomyositis. NSTIs frequently involve the deep fascia and may provoke muscle necrosis. The goal of this study was to determine the tropism and pathogenicity of these two bacterial species for muscle cells. The results revealed a high tropism of SA for myoblasts and myotubes followed by cytotoxicity as opposed to GAS that did not invade these cells. This study uncover a novel mechanism of SA contribution to NSTI with a direct muscle involvement, while in GAS NSTI this is likely indirect, for instance, secondary to vascular occlusion.

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Necrotizing Soft Tissue Infection Staphylococcus aureus but not S. pyogenes Isolates Display High Rates of Internalization and Cytotoxicity Toward Human Myoblasts

Baude

Bastien

Gillet

et al. 2019

The Journal of Infectious Diseases

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Background Necrotizing soft tissue infections (NSTIs) caused by group A Streptococcus (GAS) and occasionally by Staphylococcus aureus (SA) frequently involve the deep fascia and often lead to muscle necrosis. Methods To assess the pathogenicity of GAS and S. aureus for muscles in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA isolates were assessed in these cells. Bloodstream infections (BSI-SA) and noninvasive coagulase-negative staphylococci (CNS) isolates were used as controls. Results NSTI-SA and BSI-SA exhibited stronger internalization into human keratinocytes and myoblasts than NSTI-GAS or CNS. S. aureus internalization reached over 30% in human myoblasts due to a higher percentage of infected myoblasts (>11%) as compared to keratinocytes (<3%). Higher cytotoxicity for myoblasts of NSTI-SA as compared to BSI-SA was attributed to higher levels of psmα and RNAIII transcripts in NSTI-SA. However, the 2 groups were not discriminated at the genomic level. The cellular basis of high internalization rate in myoblasts was attributed to higher expression of α5β1 integrin in myoblasts. Major contribution of FnbpAB-integrin α5β1 pathway to internalization was confirmed by isogenic mutants. Conclusions Our findings suggest a factor in NSTI-SA severity is the strong invasiveness of S. aureus in muscle cells, a property not shared by NSTI-GAS isolates.

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Diabetes and necrotizing soft tissue infections—A prospective observational cohort study: Statistical analysis plan

Abstract: The study will provide important data on patients with NSTI and diabetes.

Cited by 3 publications

References 32 publications

Association of sarcopenia with a higher risk of infection in patients with type 2 diabetes

Association of sarcopenia with a higher risk of infection in patients with type 2 diabetes

Necrotizing Soft Tissue Infections Staphylococcus aureus - but not Streptococcus pyogenes-isolates display high rate of internalization and cytotoxicity toward human myoblasts

Necrotizing Soft Tissue Infection Staphylococcus aureus but not S. pyogenes Isolates Display High Rates of Internalization and Cytotoxicity Toward Human Myoblasts

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