scholarly journals Correlation Between Immunoglobulin Dose Administered and Plasma Neutralization of Streptococcal Superantigens in Patients With Necrotizing Soft Tissue Infections

2020 ◽  
Vol 71 (7) ◽  
pp. 1772-1775 ◽  
Author(s):  
Helena Bergsten ◽  
Martin Bruun Madsen ◽  
Francois Bergey ◽  
Ole Hyldegaard ◽  
Steinar Skrede ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Clinical Trials ◽  
T Cell ◽  
Soft Tissue ◽  
Negative Correlation ◽  
Group A Streptococcus ◽  
T Cell Proliferation ◽  
Soft Tissue Infections ◽  
Necrotizing Soft Tissue Infections ◽  
Group A

Abstract Analyses of plasma collected pre- and postadministration of intravenous immunoglobulin (IVIG) from patients with group A Streptococcus necrotizing soft tissue infections demonstrated a negative correlation between IVIG dose and toxin-triggered T-cell proliferation (r = −.67, P < .0001). One 25-g IVIG dose was sufficient to yield plasma-neutralizing activity against streptococcal superantigens. Clinical Trials Registration. NCT 01790698 and NCT02111161.

Wound Culture Utility in Negative Surgical Exploration for Necrotizing Soft Tissue Infection

2019 ◽  
Vol 85 (10) ◽  
pp. 1175-1178
Author(s):  
Erin C. Howell ◽  
Jessica A. Keeley ◽  
Alexis L. Woods ◽  
Amy H. Kaji ◽  
Molly R. Deane ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Group A Streptococcus ◽  
Necrotizing Soft Tissue Infection ◽  
Management Culture ◽  
Wound Culture ◽  
Deep Wound ◽  
Necrotizing Soft Tissue Infections ◽  
Group A ◽  
Early Surgical Intervention

Early surgical intervention decreases mortality in necrotizing soft tissue infections (NSTIs). Yet, a subset of patients will not have NSTIs (non-NSTIs) at the time of exploration. We hypothesized that NSTI and non-NSTI patients had similar causative organisms and that intraoperative wound cultures could help guide management. Culture results and outcomes were compared for all patients undergoing surgery for suspected NSTIs over a seven-year-period. Of 295 patients, 240 (81.4%) had NSTIs. Of the 55 non-NSTI patients (18.6%), 50 had cellulitis and 5 had abscesses. NSTI and non-NSTI patients had similar rates of bacteremia (20.4% vs 17.6%, P = 0.66), septic shock (15.9% vs 12.7%, P = 0.68), and mortality (10.4% vs 7.2%, P = 0.62). Wound cultures were collected more often in NSTI patients (229/240, 95.4%) than in non-NSTI patients (42/55, 76.4%, P < 0.01). Non-NSTI patients had positive deep wound cultures more than half of the time (23/42, 54.8%). The microbiologic profile was similar between groups, with Methicillin Resistant Staphylococcus aureus and Group A Streptococcus occurring with the same frequency. We advocate for deep wound cultures in all patients being evaluated operatively for NSTIs even if the exploration is considered negative because these patients have similar clinical characteristics and virulent microbiology, and culture results can help guide antimicrobial therapy.

scholarly journals Biofilm in group A streptococcal necrotizing soft tissue infections

JCI Insight ◽  
2016 ◽  
Vol 1 (10) ◽  
Author(s):  
Nikolai Siemens ◽  
Bhavya Chakrakodi ◽  
Srikanth Mairpady Shambat ◽  
Marina Morgan ◽  
Helena Bergsten ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Infections ◽  
Necrotizing Soft Tissue Infections ◽  
Group A

scholarly journals Heterogeneity in FoxP3- and GARP/LAP-Expressing T Regulatory Cells in an HLA Class II Transgenic Murine Model of Necrotizing Soft Tissue Infections by Group A Streptococcus

2018 ◽  
Vol 86 (12) ◽  
Author(s):  
Suba Nookala ◽  
Santhosh Mukundan ◽  
Alexander Fife ◽  
Jeyashree Alagarsamy ◽  
Malak Kotb
Keyword(s):  
T Cells ◽  
T Regulatory Cells ◽  
Risk Allele ◽  
Inflammatory Responses ◽  
Group A Streptococcus ◽  
Soft Tissue Infections ◽  
Regulatory Cells ◽  
Necrotizing Soft Tissue Infections ◽  
Group A

ABSTRACT Invasive group A streptococcus (GAS) infections include necrotizing soft tissue infections (NSTI) and streptococcal toxic shock syndrome (STSS). We have previously shown that host HLA class II allelic variations determine the risk for necrotizing fasciitis (NF), a dominant subgroup of NSTI, and STSS by modulating responses to GAS superantigens (SAgs). SAgs are pivotal mediators of uncontrolled T-cell activation, triggering a proinflammatory cytokine storm in the host. FoxP3-expressing CD4+ CD25+ T regulatory cells (Tregs) comprise phenotypically and functionally heterogeneous subsets with a profound ability to suppress inflammatory responses. Specifically, activated Tregs, which express glycoprotein A repetitions predominant (GARP) and display latent transforming growth factor β1 (TGF-β1) complexes (latency-associated peptide [LAP]), exhibit strong immunosuppressive functions. The significance of Tregs that may participate in suppressing inflammatory responses during NSTI is unknown. Here, we phenotypically characterized FoxP3/GARP/LAP-expressing Tregs in GAS-infected or SAg (SmeZ)-stimulated splenocytes from transgenic (tg) mice expressing human HLA-II DRB1*15 (DR15 allele associated with nonsevere NF/STSS-protective responses) or DRB1*0402/DQB1*0302 (DR4/DQ8 alleles associated with neutral risk for combined NF/STSS). We demonstrated both in vivo and in vitro that the neutral-risk allele upregulates expression of CD4+ CD25+ activated effector T cells, with a significantly lower frequency of Foxp3+/GARP+ LAP− but higher frequency of Foxp3− LAP+ Tregs than seen with the protective allele. Additional in vitro studies revealed that the presentation of SmeZ by the neutral-risk allele significantly increases proliferation and expression of effector cytokines gamma interferon (IFN-γ) and interleukin-2 (IL-2) and upregulates CD4+ CD25+ T cell receptors (TCRs) carrying specific Vβ 11 chain (TCRVβ11+) T cells and Th1 transcription factor Tbx21 mRNA levels. Our data suggest that neutral-risk alleles may drive Th1 differentiation while attenuating the induction of Tregs associated with suppressive function.

scholarly journals Genetic Architecture of Group A Streptococcal Necrotizing Soft Tissue Infections in the Mouse

2016 ◽  
Vol 12 (7) ◽  
pp. e1005732 ◽  
Author(s):  
Karthickeyan Chella Krishnan ◽  
Santhosh Mukundan ◽  
Jeyashree Alagarsamy ◽  
Junguk Hur ◽  
Suba Nookala ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Genetic Architecture ◽  
Soft Tissue Infections ◽  
Necrotizing Soft Tissue Infections ◽  
Group A

scholarly journals The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 332 ◽  
Author(s):  
Patience Shumba ◽  
Srikanth Mairpady Shambat ◽  
Nikolai Siemens
Keyword(s):  
Soft Tissue ◽  
Current Knowledge ◽  
Special Focus ◽  
Soft Tissue Infections ◽  
Gram Positive Bacteria ◽  
Necrotizing Soft Tissue Infections ◽  
Group A ◽  
Clinical Conditions ◽  
Major Pathogens

Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both Gram-positive bacteria secrete a variety of molecules, including pore-forming exotoxins, superantigens, and proteases with cytolytic and immunomodulatory functions. The present review summarizes the current knowledge about streptococcal and staphylococcal toxins in NSTIs with a special focus on their contribution to disease progression, tissue pathology, and immune evasion strategies.

scholarly journals Antibiotics in Necrotizing Soft Tissue Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1104
Author(s):  
Tomas Urbina ◽  
Keyvan Razazi ◽  
Clément Ourghanlian ◽  
Paul-Louis Woerther ◽  
Olivier Chosidow ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Antibiotic Therapy ◽  
Broad Spectrum ◽  
Bacterial Infections ◽  
Group A Streptococcus ◽  
Empirical Therapy ◽  
Antibiotic Use ◽  
Soft Tissue Infections ◽  
Beta Lactam ◽  
Necrotizing Soft Tissue Infections

Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections characterized by an extensive necrosis of skin and subcutaneous tissues. Initial urgent management of NSTIs relies on broad-spectrum antibiotic therapy, rapid surgical debridement of all infected tissues and, when present, treatment of associated organ failures in the intensive care unit. Antibiotic therapy for NSTI patients faces several challenges and should (1) carry broad-spectrum activity against gram-positive and gram-negative pathogens because of frequent polymicrobial infections, considering extended coverage for multidrug resistance in selected cases. In practice, a broad-spectrum beta-lactam antibiotic (e.g., piperacillin-tazobactam) is the mainstay of empirical therapy; (2) decrease toxin production, typically using a clindamycin combination, mainly in proven or suspected group A streptococcus infections; and (3) achieve the best possible tissue diffusion with regards to impaired regional perfusion, tissue necrosis, and pharmacokinetic and pharmacodynamic alterations. The best duration of antibiotic treatment has not been well established and is generally comprised between 7 and 15 days. This article reviews the currently available knowledge regarding antibiotic use in NSTIs.

scholarly journals Sulfamethoxazole-Trimethoprim (Cotrimoxazole) for Skin and Soft Tissue Infections Including Impetigo, Cellulitis, and Abscess

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Asha C Bowen ◽  
Jonathan R Carapetis ◽  
Bart J Currie ◽  
Vance Fowler ◽  
Henry F Chambers ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Observational Studies ◽  
Group A Streptococcus ◽  
Controlled Trials ◽  
Soft Tissue Infections ◽  
Randomized Controlled ◽  
Significant Burden ◽  
Full Text Review ◽  
Group A

Abstract Skin and soft tissue infections (SSTI) affect millions of people globally, which represents a significant burden on ambulatory care and hospital settings. The role of sulfamethoxazole-trimethoprim (SXT) in SSTI treatment, particularly when group A Streptococcus (GAS) is involved, is controversial. We conducted a systematic review of clinical trials and observational studies that address the utility of SXT for SSTI treatment, caused by either GAS or Staphylococcus aureus, including methicillin-resistant (MRSA). We identified 196 studies, and 15 underwent full text review by 2 reviewers. Observational studies, which mainly focused on SSTI due to S aureus, supported the use of SXT when compared with clindamycin or β-lactams. Of 10 randomized controlled trials, 8 demonstrated the efficacy of SXT for SSTI treatment including conditions involving GAS. These findings support SXT use for treatment of impetigo and purulent cellulitis (without an additional β-lactam agent) and abscess and wound infection. For nonpurulent cellulitis, β-lactams remain the treatment of choice.

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