Staphylococcal Toxic Shock Research Articles

Choc toxique staphylococcique menstruel en France : ce que vous devez savoir

AbstractAround 30 cases of menstrual staphylococcal toxic shock syndrome are reported each year in France. This is a severe illness that, if not rapidly treated, can result in hospitalization in intensive care and, and, less commonly, death. The initial symptoms include fever, chills, rash and digestive disorders. This syndrome occurs during menstruation, in women who use intravaginal sanitary protection (tampon, menstrual cup, etc.) and who have a vaginal carriage of Staphylococcus aureus producing toxic shock syndrome toxin 1 (TSST-1). This superantigenic toxin, produced in the vagina, non-specifically activates the immune system, leading to the massive release of pro-inflammatory cytokines. Diagnosis of this syndrome is based on a combination of clinical and biological criteria. Biological diagnosis typically involves the isolation of a TSST-1-producing strain of S. aureus, which is usually obtained from a vaginal swab. The removal of intravaginal protection, administration of an anti-staphylococcal beta-lactam antibiotic and an antitoxin such as clindamycin can reduce mortality and sequelae of the disease.

Tofacitinib Treatment Suppresses CD4+ T-Cell Activation and Th1 Response, Contributing to Protection against Staphylococcal Toxic Shock.

Staphylococcal toxic shock syndrome (STSS) is a rare, yet potentially fatal disease caused by Staphylococcus aureus (S. aureus) enterotoxins, known as superantigens, which trigger an intense immune response. Our previous study demonstrated the protective effect of tofacitinib against murine toxin-induced shock and a beneficial effect against S. aureus sepsis. In the current study, we examined the effects of tofacitinib on T-cell response in peripheral blood using a mouse model of enterotoxin-induced shock. Our data revealed that tofacitinib suppresses the activation of both CD4+ and CD8+ T cells in peripheral blood. Furthermore, both gene and protein levels of Th1 cytokines were downregulated by tofacitinib treatment in mice with enterotoxin-induced shock. Importantly, we demonstrated that CD4+ cells, but not CD8+ cells, are pathogenic in mice with enterotoxin-induced shock. In conclusion, our findings suggest that tofacitinib treatment suppresses CD4+ T-cell activation and Th1 response, thereby aiding in protection against staphylococcal toxic shock in mice. This insight may guide the future development of novel therapies for STSS.

Long-term outcomes of patients with toxic shock syndrome: A matched cohort study

We examined long-term outcomes of toxic shock syndrome. We conducted a matched cohort study of 630 patients with toxic shock syndrome and 5009 healthy controls between 2006 and 2021 in Quebec, Canada. Outcomes included hospitalization for renal, cardiovascular, hepatic, and other morbidity during 15 years of follow-up. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the risk of these outcomes over time, comparing patients with toxic shock syndrome relative to matched controls. Compared with healthy controls, rehospitalization rates at 15 years were higher for men with toxic shock syndrome (52.0 vs 30.0 per 100)but not for women (38.7 vs 45.6 per 100). In men, toxic shock syndrome was associated with an elevated risk of renal (HR 17.43, 95% CI 6.35-47.82), cardiovascular (HR 2.57; 95% CI 1.52-4.34), and hepatic hospitalization (HR 19.83, 95% CI 4.72-83.34). In women, toxic shock syndrome was associated with renal hospitalization (HR 4.71, 95% CI 1.94-11.45). Streptococcal toxic shock was associated with a greater risk of rehospitalization than staphylococcal toxic shock. Toxic shock syndrome is associated with rehospitalization up to 15 years later, especially in men. These patients may benefit from continued follow-up to prevent long-term morbidity.

Fatal, non-menstrual staphylococcal toxic shock syndrome associated with dental implant

Staphylococcal toxic shock syndrome (TSS) is a life-threatening disease that characterized by rapid onset of fever, rash, hypotension, and multi-organ failure.A 58-year-old man presented to the emergency department (ED) with complaints of fatigue, myalgia, and blurred vision which had progressed over 48 hours. His medical history included hypertension and dental implant treatment that lasted 15 days. Despite aggressive medical treatment, which included multiple vasopressors, continuous renal replacement therapy in combination with CytoSorb and broad-spectrum antibiotics, he died 16 hours after admission to the intensive care unit. was detected in his blood and ETA cultures after the patient's death.Staphylococcal TSS is classified as menstrual and non-menstrual. Non-menstrual TSS cases have been documented with increasing frequency in the literature. We present a case of Staphylococcal TSS in a 58-year-old male patient who had a dental surgery history. Our patient died within a few hours after admission to the ICU with signs of multi-organ failure. We wanted to draw attention to this issue by presenting our patient.

Pediatric Leptospirosis: A Case Report and Review of Literature.

Leptospirosis, a zoonosis, is characterized by a wide range of clinical and laboratory findings, varying from self-limiting infection to potentially fatal disease. Leptospirosis-related clinical manifestations, except for Weil's disease, may often be overlooked due to their nonspecificity in children. Additionally, many health-care professionals lack awareness of leptospirosis. This paper presents a case of leptospirosis that was initially misdiagnosed as staphylococcal toxic shock syndrome. The literature on this topic is also reviewed.

Gait Acquisition with a Quadrilateral Socket after Ultra-short Transfemoral Amputation because of Staphylococcal Toxic Shock Syndrome

Gait Acquisition with a Quadrilateral Socket after Ultra-short Transfemoral Amputation because of Staphylococcal Toxic Shock Syndrome

Antimicrobial peptidase lysostaphin at subinhibitory concentrations modulates staphylococcal adherence, biofilm formation, and toxin production

BackgroundThe ability of antimicrobial agents to affect microbial adherence to eukaryotic cell surfaces is a promising antivirulence strategy for combating the global threat of antimicrobial resistance. Inadequate use of antimicrobials has led to widespread instances of suboptimal antibiotic concentrations around infection sites. Therefore, we aimed to examine the varying effect of an antimicrobial peptidase lysostaphin (APLss) on staphylococcal adherence to host cells, biofilm biomass formation, and toxin production as a probable method for mitigating staphylococcal virulence.ResultsInitially, soluble expression in E. coli and subsequent purification by immobilized-Ni2+ affinity chromatography (IMAC) enabled us to successfully produce a large quantity of highly pure ~ 28-kDa His-tagged mature APLss. The purified protein exhibited potent inhibitory effects against both methicillin-sensitive and methicillin-resistant staphylococcal strains, with minimal inhibitory concentrations (MICs) ranging from 1 to 2 µg/mL, and ultrastructural analysis revealed that APLss-induced concentration-specific changes in the morphological architecture of staphylococcal surface membranes. Furthermore, spectrophotometric and fluorescence microscopy revealed that incubating staphylococcal strains with sub-MIC and MIC of APLss significantly inhibited staphylococcal adherence to human vaginal epithelial cells and biofilm biomass formation. Ultimately, transcriptional investigations revealed that APLss inhibited the expression of agrA (quorum sensing effector) and other virulence genes related to toxin synthesis.ConclusionsOverall, APLss dose-dependently inhibited adhesion to host cell surfaces and staphylococcal-associated virulence factors, warranting further investigation as a potential anti-staphylococcal agent with an antiadhesive mechanism of action using in vivo models of staphylococcal toxic shock syndrome.

Cases of Menstrual Toxic Shock Syndrome in the Czech Republic in 1997–2022

Staphylococcal toxic shock syndrome (TSS) is a serious condition that can be life threatening. There are two forms of this disease: menstrual and non-menstrual. In the 25 years from 1997 to 2022, 105 cases of TSS related to menstruation were registered at the National Reference Laboratory for Staphylococci of the National Institute of Public Health (NIPH) in Prague. All the patients recovered, but one third of the them had a severe course of the illness including intensive care unit admission reported in their discharge summaries. All the patients except for one had a history of vaginal tampon use, in the remaining one it was a menstrual cup.

The safety assessment of tampons: illustration of a comprehensive approach for four different products.

We illustrate a comprehensive tampon safety assessment approach that assures products can be used safely. Material biocompatibility, vaginal mucosa assessment, vaginal microbiome evaluation, and in vitro assessment of potential risk of staphylococcal toxic shock syndrome expressed through growth of Staphylococcus aureus (S. aureus) and production of TSST-1 are the four essential portions of the approach. Post-marketing surveillance informs of possible health effects that warrant follow up. The approach meets or exceeds US and international regulatory guidance and is described through the example of four tampon products. Each product is comprised mostly of large molecular weight components (cotton, rayon, polymers) that cannot pass the vaginal mucosa, are widely used across the industry, and replete with a vast body of safety data and a long history of safe use in the category. Quantitative risk assessment of all small molecular weight components assured a sufficient margin of safety supporting their use. Vaginal mucosa assessment confirmed that pressure points, rough edges and/or sharp contact points were absent. A randomized cross-over clinical trial (ClinicalTrials.gov Identifier: NCT03478371) revealed favorable comfort ratings, and few complaints of irritation, burning, stinging, or discomfort upon insertion, wear, and removal. Adverse events were few, mild in severity, self-limited and resolved without treatment. Vaginal microbiota assessment in vitro presented no adverse effect on microbial growth. Culture-independent microbiome analyses from vaginal swab samples obtained during the clinical trial showed no differences attributable to tampon usage, but instead due to statistically significant subject-to-subject variability. Growth of S. aureus and TSST-1 toxin production in the presence of any of the four products in vitro were statistically significantly reduced when compared to medium control alone. The data from the four elements of the comprehensive safety assessment approach illustrated herein confirm that tampons evaluated using this system can be used safely for menstrual protection. A post-marketing surveillance system that monitors and responds to in-market experiences indicated in-use tolerability of the product among consumers, thus confirming the conclusions of the pre-marketing safety assessment.

Staphylococcal toxic shock syndrome.

Toxic Shock Syndrome (TSS) is a severe acute disease characterized by high fever, hypotension, rash, multiple organ dysfunction and desquamation during convalescence. TSS is caused by toxin-producing strains of Staphylococcus aureus orStreptococcus pyogenes. TSS remains a rare but severe disease. Early diagnosis is important because specific treatments with antitoxin effects must be started as soon as possible.This manuscript presents a set of images that illustrate the main findings in the peripheral blood film of a patient with TSS.

Staphylococcal Enterotoxin B and C Mutants and Vaccine Toxoids.

Three mutants individually of both staphylococcal enterotoxins B and C were prepared by site-specific mutagenesis of enterotoxin amino acids that contact host T lymphocyte immune cell receptor sites (N23A, Q210A, and N23A/Q210A); these amino acids are shared between the two enterotoxins, and mutations reduce the interaction with the variable part of the β-chain of the T lymphocyte receptor. The mutant proteins, as expressed in Staphylococcus aureus RN4220, lacked biological toxicity as measured by the loss of (i) stimulation of rabbit splenocyte proliferation, (ii) pyrogenicity, and (iii) the ability to enhance the lethality of endotoxin shock, compared to wild-type enterotoxins. In addition, the mutants were able to vaccinate rabbits against pyrogenicity, the enhancement of endotoxin shock, and lethality in a pneumonia model when animals were challenged with methicillin-resistant S. aureus. Three vaccine injections (one primary and two boosters) protected rabbits for at least 3.5 months postvaccination when challenged with wild-type enterotoxins (last time point tested). These mutant proteins have the potential to function as toxoid vaccines against these two causes of nonmenstrual toxic shock syndrome (TSS). IMPORTANCE Toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxins B and C cause the majority of cases of staphylococcal toxic shock syndrome. Previously, vaccine toxoids of TSST-1 have been prepared. In this study, vaccine toxoids of enterotoxins B and C were prepared. The toxoids lost biological toxicity but were able to vaccinate rabbits against lethal TSS.

A Rare Presentation of Fulminant Toxic Shock Syndrome in a Healthy 10-Year-Old Male Patient

Staphylococcal toxic shock syndrome (STSS) is characterized by acute, progressive illness with fever, rapid-onset hypotension, and multisystem organ failure. The clinical course of STSS is attributable to host response to exotoxins with superantigenic properties. Fulminant staphylococcal infection is often associated with a deep focus of infection. In this report, we present a 10-year-old boy with multisystem organ failure as a result of STSS, a rare fatal complication following soft tissue injury. The rapid and fulminant progression of the disease in our patient precluded early timely diagnosis of STSS that may have allowed for the initiation of life-saving supportive intervention. Furthermore, the rapidly developing STSS occurred without an identifiable infectious source. The diagnosis of STSS was made upon the sum total of the clinical presentation, laboratory and autopsy findings, and antemortem and postmortem microbiology studies. It is crucial for health care providers to be aware of the possibility of STSS, even in the absence of overt focal infections and risk factors. A high index of suspicion for STSS should be present in critically ill patients presenting with a precipitous course of sepsis, septic shock, or systemic inflammatory response syndrome (SIRS).

Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes.

Staphylococcus aureus, a gram-positive bacterium, causes toxic shock through the production of superantigenic toxins (sAgs) known as Staphylococcal enterotoxins (SE), serotypes A-J (SEA, SEB, etc.), and toxic shock syndrome toxin-1 (TSST-1). The chronology of host transcriptomic events that characterizes the response to the pathogenesis of superantigenic toxicity remains uncertain. The focus of this study was to elucidate time-resolved host responses to three toxins of the superantigenic family, namely SEA, SEB, and TSST-1. Due to the evolving critical role of melanocytes in the host’s immune response against environmental harmful elements, we investigated herein the transcriptomic responses of melanocytes after treatment with 200 ng/mL of SEA, SEB, or TSST-1 for 0.5, 2, 6, 12, 24, or 48 h. Functional analysis indicated that each of these three toxins induced a specific transcriptional pattern. In particular, the time-resolved transcriptional modulations due to SEB exposure were very distinct from those induced by SEA and TSST-1. The three superantigens share some similarities in the mechanisms underlying apoptosis, innate immunity, and other biological processes. Superantigen-specific signatures were determined for the functional dynamics related to necrosis, cytokine production, and acute-phase response. These differentially regulated networks can be targeted for therapeutic intervention and marked as the distinguishing factors for the three sAgs.

The Association Between Onset of Staphylococcal Non-menstrual Toxic Shock Syndrome With Inducibility of Toxic Shock Syndrome Toxin-1 Production.

Non-menstrual toxic shock syndrome (non-mTSS) is a life-threatening disease caused by Staphylococcus aureus strains producing superantigens, such as staphylococcal enterotoxins A, B, C, and toxic shock syndrome toxin-1 (TSST-1). However, little is known about why the TSS cases are rare, although S. aureus strains frequently carry a tst gene, which encodes TSST-1. To answer this question, the amount of TSST-1 produced by 541 clinical isolates was measured in both the presence and absence of serum supplementation to growth media. Then a set of S. aureus strains with similar genetic backgrounds isolated from patients presenting with non-mTSS and those with clinical manifestations other than non-mTSS was compared for their TSST-1 inducibility by human serum, and their whole-genome sequences were determined. Subsequently, the association of mutations identified in the tst promoter of non-mTSS strains with TSST-1 inducibility by human serum was evaluated by constructing promoter replacement mutants and green fluorescent protein (GFP) reporter recombinants. Results showed that 39 out of 541 clinical isolates (7.2%), including strains isolated from non-mTSS patients, had enhanced production of TSST-1 in the presence of serum. TSST-1 inducibility by human serum was more clearly seen in non-mTSS strains of clonal complex (CC)-5. Moreover, the whole-genome sequence analysis identified a set of sequence variations at a putative SarA-binding site of the tst promoter. This sequence variation was proven to be partially responsible for the induction of TSST-1 production by human serum. We conclude that the onset of staphylococcal toxic shock syndrome caused by TSST-1-producing CC-5 strains seem at least partially initiated by serum induction of TSST-1, which is regulated by the mutation of putative SarA-binding site at the tst promoter.

Systemic infections associated with tattoos or permanent makeup: A systematic review

IntroductionThe aim of this article is to summarize published information on systemic infective complications of tattoos to gain an update of the current picture. MethodsA literature search was performed in PubMed database (2009–2019), and compared with a search without year restriction. Eligibility criteria were studies on systemic tattoo-related infections, including case reports, case series, outbreak investigations, reviews, and systematic reviews. ResultsWe identified 17 manuscripts with systemic infections between 2009 and 2019, with one reported fatality. In contrast to the historical records, no reports of systemic tuberculosis, syphilis or viral (hepatitis or HIV) infections were reported within the study period. A few sporadic cases or Mycobacterium leprae (India) or regional lymphadenopathy associated with skin lesions in non-tuberculosis mycobacteria were identified. Persistent fever with rigour was common in bacterial bloodstream infections. One episode of staphylococcal toxic shock syndrome and several episodes of septic shock were reported, associated with cellulitis or necrotizing fasciitis within two weeks of the procedure, predominantly caused by pyogenic bacteria (S. aureus or streptococcus). Identification of lung or systemic embolisms in the absence of local symptoms, was indicative of (right or left) infective endocarditis. ConclusionsBacterial bloodstream infections should be considered in subjects developing fever and rigour after tattoos, regardless of local symptoms. A shift in causative organisms has been documented, when comparing with historical reports. NTM are emerging organisms causing lymphadenopathy. Strict hygiene conditions are essential when performing a tattoo.

Post-surgical staphylococcal toxic shock syndrome in pediatrics: A case report

IntroductionToxic shock syndrome (TSS) is a rare but serious, life-threatening medical condition and potentially lethal if not detected and treated early. It is mainly caused by a toxin called toxin-1 produced by Staphylococcus aureus, and characterized by fever, hypotension, rash, skin desquamation and multisystem involvement.Case presentationHerein, we describe a nine-month-old male patient who presented to the hospital complaining of fever, vomiting and hypoactivity on day one post-orchidopexy. During hospitalization, his condition began to deteriorate with signs and symptoms of multisystemic failure. Laboratory tests and radiological images were done, leading to the decision to reopen and drain the surgical wound. Wound and nasal swabs were cultured and showed S. aureus infection, and the diagnosis of toxic shock syndrome was confirmed.DiscussionTSS is a systemic illness resulting from overwhelming host response to bacterial exotoxins, that cause T cells activation and the release of pro-inflammatory cytokines (IL-1 and TNF-α causing fever, hypotension, and tissue injury). Also, it can present with CNS signs that may be misdiagnosed with meningitis in pediatrics.It requires early identification and treatment despite its rarity with mortality rate of 81% even with treatment.The patient's presentation, examination and laboratories tests with the blood and wound cultures were highly suggestive for this condition.ConclusionPhysicians must maintain a high index of suspicion for TSS, as early diagnosis and treatment make a difference. This condition shouldn't be excluded even in young age patients or after simple procedure as in our case in which TSS occurred after orchidopexy.

Intravenous Immunoglobulin Use In Critically Ill Children.

Purpose: The use of intravenous immunoglobulins (IVIG) has increased significantly in the last decade causing challenges for blood suppliers to respond to the demand. Indications for which IVIG infusion should be given to critically ill children remain unclear. The objective of this study is to characterize the epidemiology of IVIG use in this population. Methods: We performed a single-center retrospective cohort study of all patients aged between 3 days and 18 years who received at least one IVIG infusion while hospitalized in the pediatric intensive care unit of the Centre hospitalier universitaire (CHU) Sainte-Justine, Montréal Quebec (Canada) between January 1, 2013 and December 31, 2018. Results: One hundred and seventy-two patients received a total of 342 IVIG infusions over the study period. Most common indications for IVIG infusions were staphylococcal or streptococcal toxic shock syndrome (n=53/342, 15.5%), immunoglobulin replacement in chylothorax (n=37/342, 10.9%), prophylaxis following bone marrow transplantation (n=31/342, 9.1%), myocarditis (n=25/342, 7.3%) and post-solid organ transplant complications (n=21/342, 6.1%). The median dose of IVIG per infusion was 0.95 g/kg (IQR 0.5-1.0) and median number of IVIG infusions per patient was one (IQR: 1-2). Seventy-nine percent of IVIG infusions given were administrated for off-label indications with regards to Health Canada recommendations. Conclusion: This study identified the most common indications for IVIG infusion in critically ill children in a tertiary care pediatric intensive care unit. Given the costs, the known adverse events associated with IVIG and the pressure that blood suppliers are facing to meet the demands, clinical trials are needed to evaluate the efficacy and safety of IVIG in conditions where use is significant.

Systemic infections associated with tattoos or permanent makeup: A systematic review

IntroductionThe aim of this article is to summarize published information on systemic infective complications of tattoos to gain an update of the current picture. MethodsA literature search was performed in PubMed database (2009–2019), and compared with a search without year restriction. Eligibility criteria were studies on systemic tattoo-related infections, including case reports, case series, outbreak investigations, reviews, and systematic reviews. ResultsWe identified 17 manuscripts with systemic infections between 2009 and 2019, with one reported fatality. In contrast to the historical records, no reports of systemic tuberculosis, syphilis or viral (hepatitis or HIV) infections were reported within the study period. A few sporadic cases or Mycobacterium leprae (India) or regional lymphadenopathy associated with skin lesions in non-tuberculosis mycobacteria were identified. Persistent fever with rigour was common in bacterial bloodstream infections. One episode of staphylococcal toxic shock syndrome and several episodes of septic shock were reported, associated with cellulitis or necrotizing fasciitis within two weeks of the procedure, predominantly caused by pyogenic bacteria (S. aureus or streptococcus). Identification of lung or systemic embolisms in the absence of local symptoms, was indicative of (right or left) infective endocarditis. ConclusionsBacterial bloodstream infections should be considered in subjects developing fever and rigour after tattoos, regardless of local symptoms. A shift in causative organisms has been documented, when comparing with historical reports. NTM are emerging organisms causing lymphadenopathy. Strict hygiene conditions are essential when performing a tattoo.

COVID-19 and the clinical course of rheumatic manifestations.

The manifestations of COVID-19 have been evolving over time. Various post-COVID-19 syndromes are being recognised. Various viruses have been implicated in the pathogenesis of autoimmune diseases, and we expect a similar outcome with the severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2). The SARS-CoV-2 virus penetrates various tissues and organs and has a predisposition to lead to endotheliitis that may cause vascular manifestations including thrombosis. SARS-CoV-2 has been shown to activate Toll-like receptors and the complement system. It perpetuates NETosis and leads to autoantibody formation. These predispose to systemic autoimmunity. Both reactive arthritis and connective tissue disorders such as lupus and inflammatory myositis have been reported after COVID-19. Other reported autoimmune disorders include haemolytic anaemia, immune thrombocytopenia, cutaneous vasculitis, and Guillain Barré–like acute demyelinating disorders. The multi-system inflammatory syndrome in children and its adult counterpart are another post-COVID-19 entity that presents as an admixture of Kawasaki disease and staphylococcal toxic shock syndrome. Patients with preexisting rheumatic diseases may flare during the SARS-CoV-2 infection. They may develop novel autoimmune features also. The immune-suppressants used during the acute COVID-19 illness may confound the outcomes whereas comorbidities present in patients with rheumatic diseases may mask them. There is an urgent need to follow-up patients recovering from COVID and monitor autoantibody production in the context of rheumatic manifestations.Key Points• COVID-19 is associated with both innate and acquired immune reactions and production of various autoantibodies.• Various immune-mediated manifestations such as arthritis, myositis, haemolytic anaemia, thrombocytopenia, and acute demyelination may develop after COVID-19.• Longitudinal cohort data are warranted to describe, predict, and test prevent various rheumatic manifestations in post-COVID-19 subjects.

COVID-19 and children

Most children with a proven coronavirus disease (COVID-19) infection are asymptomatic or have mild symptoms. However, a small number of children have been identified in the past 2 months with developed significant multisystem inflammatory response. All children were treated according to standard protocols. Children with this disease may require hospitalization in pediatric intensive care unit with a multisystem team approach to the disease, which includes pediatricians, infectologists, cardiologists, rheumatologists, immunologists, and epidemiologists. This extremely rare disease is curable if diagnosed in time. This rare syndrome has features in common with other pediatric inflammatory diseases including Kawasaki syndrome, staphylococcal and streptococcal toxic shock syndrome, bacterial sepsis, macrophage activation syndrome, and may present with unusual abdominal pain including elevated inflammation markers. Early recognition of this disease by a pediatrician or family doctor specialist is crucial for the timely treatment and outcome of the disease.