Cases Of Streptococcal Toxic Shock Syndrome Research Articles

Characteristics of Streptococcal Toxic Shock Syndrome Caused by Different Beta-hemolytic Streptococci Species: A Single-center Retrospective Study.

Streptococcal toxic shock syndrome (STSS) is a life-threatening condition caused by beta-hemolytic streptococci (BHS). Streptococcus pyogenes is the main causative agent of this disease; other BHS such as Streptococcus agalactiae or Streptococcus dysgalactiae could also cause STSS. However, the clinical characteristics of STSS caused by other types of BHS remain poorly understood. In this study, we evaluated the likelihood of STSS development in various streptococcal species. We conducted a retrospective observational study using adult medical records of patients with invasive BHS in a tertiary care institution from 2002 to 2022 and classified them into STSS or non-STSS groups. Multivariable analysis of bacterial species adjusted for age and diabetes mellitus was conducted. S pyogenes cases were propensity-matched (1:4) to non-pyogenes BHS cases. A total of 43 STSS and 285 non-STSS cases were identified. S pyogenes, S agalactiae, and S dysgalactiae accounted for 17, 13, and 13 STSS cases, respectively. The crude mortality of STSS was approximately 35% in all groups. A multivariable analysis suggested that STSS was less frequent in S agalactiae and S dysgalactiae cases with odds ratio 0.24 (95% confidence interval [CI], 0.10-0.54; P < .001) and 0.23 (95% CI, .10-.55; P < .001), respectively. Propensity score matching showed that S pyogenes caused STSS more frequently than other BHS cases with an odds ratio of 3.28 (95% CI 1.21-8.77; P = .010). This study described and compared the clinical characteristics of STSS caused by different BHS. We demonstrated that S pyogenes caused STSS more often than other BHS.

Evaluating antibiotic regimens for streptococcal toxic shock syndrome in children.

Streptococcal toxic shock syndrome (STSS) is a severe consequence of infections from Streptococcus pyogenes. The early identification and timely intervention with appropriate anti-infective agents are pivotal for managing pediatric STSS. This study evaluates the effectiveness of various treatment regimens for STSS in children. Clinical data of children with STSS resulting from β-hemolytic streptococcal infections in two hospitals were retrospectively analyzed from January 2009 to April 2023. Additionally, literature from the China National Knowledge Infrastructure on pediatric STSS was examined. Antimicrobial treatments were categorized into four groups based on their compositions, with an additional categorization for adjunct therapeutic drugs. Of 32 confirmed STSS cases, all displayed sensitivity to ampicillin, β-lactam antibiotics, and vancomycin, but resistance to clindamycin, erythromycin, and tetracycline. From the literature, 23 studies with 50 cases were extracted, leading to a total of 82 patients for evaluation. The efficacy rates varied significantly among the four treatment groups. Notably, the standard penicillin-containing group exhibited the highest efficacy (86.4%), while the group with macrolides/unused antibiotics registered a 0% efficacy rate. The other two groups demonstrated efficacy rates of 32.1% and 42.3%. For pediatric STSS, Streptococcus pyogenes shows notable sensitivity to ampicillin. Implementing timely β-lactam antibiotics, specifically penicillin, in conjunction with clindamycin and intravenous immunoglobulins enhances the treatment success rate.

Serotype Distribution and Antimicrobial Resistance of Streptococcus agalactiae Isolates in Nonpregnant Adults with Streptococcal Toxic Shock Syndrome in Japan in 2014 to 2021.

The incidence of streptococcal toxic shock syndrome (STSS) due to group B Streptococcus (GBS) has been increasing annually in Japan and is becoming a serious challenge. Furthermore, in recent years, penicillin- or clindamycin-resistant strains used in treating streptococcal toxic shock syndrome have been reported. However, no report analyzed >100 isolates of group B Streptococcus causing streptococcal toxic shock syndrome. Therefore, we aimed to perform serotyping and antimicrobial susceptibility testing of 268 isolated group B Streptococcus strains from streptococcal toxic shock syndrome cases involving nonpregnant adult patients in Japan between 2014 and 2021. The most prevalent serotype was Ib, followed by serotypes V, III, and Ia. Seven isolates were resistant to penicillin G, and 17.9% (48 isolates) were resistant to clindamycin. Of the penicillin-resistant group B Streptococcus isolates, 71.4% (5 isolates) were clindamycin resistant. In addition, group B Streptococcus strains resistant to penicillin and clindamycin were isolated from patients with streptococcal toxic shock syndrome. Therefore, before these strains become prevalent, introduction of the group B Streptococcus vaccine is essential for disease prevention. IMPORTANCE Group B Streptococcus (GBS) has been increasingly associated with invasive disease in nonpregnant adults. Such infections are responsible for substantial morbidity and mortality, particularly in individuals with underlying chronic conditions. Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multiorgan failure, and high mortality. In this study, we assessed 268 GBS-related STSS cases in nonpregnant adults in Japan between 2014 and 2021. Serotype Ib was the most prevalent, followed by serotypes V, III, and Ia, which were identified in more than 80% of STSS isolates. We found that 48 clindamycin-resistant strains and 7 penicillin G-resistant strains were isolated between 2014 and 2021. We believe that our study makes a significant contribution to the literature because we show that the GBS vaccine, particularly the hexavalent conjugate vaccine, is important to reduce the number of patients with STSS.

Drug treatment efficacy in 32 children with streptococcal toxic shock syndrome

To study the efficacy of different drug treatment regimens in children with streptococcal toxic shock syndrome (STSS). Clinical data of children diagnosed with STSS confirmed by bacterial culture and treated in Hunan Children's Hospital and Chenzhou First People's Hospital from January 2009 to April 2023 were retrospectively collected. The efficacy of different drug treatment regimens was analyzed. The children were divided into four groups based on the treatment regimens: standard group (regimens containing penicillin), Group A (carbapenem + glycopeptides/linezolid), Group B (carbapenems, broad-spectrum antibiotics, glycopeptides/linezolid used alone or in combination, excluding the regimens in Group A), and Group C (macrolides/not receiving antimicrobial drugs). A total of 32 cases of STSS were included. Antimicrobial susceptibility testing showed that all strains were sensitive to beta-lactam antibiotics such as ampicillin and vancomycin, while resistant to clindamycin, erythromycin, and tetracycline. There was a statistically significant difference in the efficacy rate among the four groups (P<0.05). The standard group exhibited the highest efficacy rate (100%), while the efficacy rates for Group A, Group B, and Group C were 40%, 40%, and 0%, respectively. The use of antimicrobial regimens containing penicillin can improve the therapeutic efficacy of STSS in children.

Molecular characterization and antimicrobial resistance of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2013 to 2018

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and puerperal sepsis and shows high mortality. Its primary cause is group A streptococcus (GAS, Streptococcus pyogenes). In this study, we genotyped the cell-surface M virulence protein gene (emm) from 621 GAS isolates obtained from patients with STSS in Japan in 2013–2018 and performed antimicrobial susceptibility testing using the broth microdilution method. The predominant emm type was found to be 1, followed by 89, 12, and 3, which were identified in more than 70 % of STSS isolates. The proportions of emm3 and emm89 increased from 2.4 % and 12.0 %, respectively, during 2010–2012 to 5.6 % and 23.3 % during 2013–2018. In contrast, the proportion of emm1 decreased from 60.6 % to 39.3 % during the same two periods. Some emm types showed increasing proportions and were not isolated from patients with STSS in 2010–2012. Among these, an emm76 type increased in prevalence and was not included in the 30-valent M protein-based vaccine. Continual investigation of changes in the epidemiology of GAS which causes STSS can provide useful monitoring information such as future vaccination strategies and the emergence status of antimicrobial-resistant bacteria.

„Tempus fugit, venit mors” – a streptococcalis toxikus sokk szindrómáról egy eset kapcsán

Streptococcal toxic shock syndrome (STSS) is a hyperacute, life-threatening illness, a complication of invasive streptococcal (mostly group A, rarely groups B, G or C) infection. There is no portal of entry (skin, vagina, pharynx) in nearly half of the STSS cases. The initial signs and symptoms (fever, flu-like complaints, hypotension) are scarce and aspecific, but because of its rapid progression and poor prognosis, early high level of suspicion is necessary. Management has 3 crucial points: initiation of anti-streptococcal regimen (and intravenous immunoglobulin in some cases), aggressive intensive care support of multi-organ failure, and surgical control of the infective source. In this article, we present a case of a patient succumbing to streptococcal toxic shock syndrome which was preceded by primary S. pyogenes bacteremia, and review the key points of this potentially fatal disease for practising clinicians. Orv Hetil. 2019; 160(48): 1887-1893.

Streptococcal toxic shock syndrome caused by Streptococcus pyogenes: a retrospective study of 15 pediatric cases

Objective: To improve the understanding of clinical characteristics of streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes (S. pyogenes) in children. Methods: A retrospective study was conducted to analyze the clinical data of STSS caused by S. pyogenes (culture-confirmed) in 7 tertiary hospitals during 2010-2017 in China. Clinical and laboratory data were collected by reviewing the medical records. Results: Fifteen cases of STSS, including 9 males, were confirmed and the ages of the patients ranged from 6 months to 15 years, with median age of 3 years. All cases had the positive blood culture for S. pyogenes and only 3 cases had short course of β-lactam treatment before blood culture. Medical evaluation was initiated within (5.1±4.6) days after symptom onset. All patients had fever, and 13 patients had multiple organ dysfunction and 10 patients had disseminated intravascular coagulationl (DIC). Twelve cases had severe pneumonia with or without skin and (or) soft tissue infections. Underlying conditions included giant hemangioma of the skin in 2 patients and varicella in 1 patient. All isolated strains in 14 cases were sensitive to penicillin G, ceftriaxone/cefotaxime, vancomycin, but 12 and 13 isolates were resistant to clindamycin and erythromycin, respectively. Eight patients died, and 5 of them died within 24 hours after admission. One patient was lost to follow-up after intended discharge against medical advice. Conclusion: STSS caused by S. pyogenes in children is a severe syndrome with rapid clinical progression and high mortality rate, and thus the pediatricians should be aware of STSS and immediately initiate aggressive treatment for the suspected cases.

Increased prevalence of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2010 to 2012.

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and high mortality. In Japan, appropriate notification measures based on the Infectious Disease Control law are mandatory for cases of STSS caused by β-haemolytic streptococcus. STSS is mainly caused by group A streptococcus (GAS). Although an average of 60-70 cases of GAS-induced STSS are reported annually, 143 cases were recorded in 2011. To determine the reason behind this marked increase, we characterized the emm genotype of 249 GAS isolates from STSS patients in Japan from 2010 to 2012 and performed antimicrobial susceptibility testing. The predominant genotype was found to be emm1, followed by emm89, emm12, emm28, emm3, and emm90. These six genotypes constituted more than 90% of the STSS isolates. The number of emm1, emm89, emm12, and emm28 isolates increased concomitantly with the increase in the total number of STSS cases. In particular, the number of mefA-positive emm1 isolates has escalated since 2011. Thus, the increase in the incidence of STSS can be attributed to an increase in the number of cases associated with specific genotypes.

In vivo and in vitro detection of a superantigenic toxin Vbeta signature in two forms of streptococcal toxic shock syndrome

The aim of this study was to examine the production of superantigenic toxins in vivo and in vitro in two patients with streptococcal toxic shock syndrome (TSS). In the first patient, a woman with puerperal fever and Streptococcus pyogenes peritonitis, flow cytometry of blood cells and in vitro studies of the isolate showed massive expansion of Vbeta 2-positive T cells corresponding to SpeC production. In the second case, involving a patient with streptococcal TSS and purpura fulminans following non-steroidal anti-inflammatory drug (NSAID) therapy, no Vbeta expansion of T cells was observed in vivo, but the SpeC Vbeta signature was also detected in vitro. In this latter patient, NSAID administration and/or severe disseminated infection might partly explain the absence of Vbeta T cell expansion in vivo. Combined in vivo and in vitro detection of a superantigenic toxin Vbeta signature may be useful to determine which superantigenic toxin is involved in individual cases of streptococcal TSS.

Outbreak of Invasive Group A Streptococcal Disease Among Children Attending a Day-Care Center

Most cases of invasive group A streptococcal (GAS) disease arise sporadically in the community, but outbreaks of severe invasive GAS infections have been reported in closed environments, such as military populations, family communities and hospitals. An outbreak of invasive GAS disease involving 3 cases of streptococcal toxic shock syndrome (TSS), one with a fatal course, occurred among children attending a day-care center located in Cantabria, Northern Spain. To determine the characteristics of GAS isolates obtained from the outbreak environment. GAS isolates obtained from children attending the same day-care facility, staff members, and family contacts were assayed for emm typing, pulse-field gel electrophoresis (PFGE), and toxin-gene content. One isolate obtained from the fatal case was also characterized by multilocus sequence typing. Antimicrobial susceptibility testing was done. Strains from patients unrelated to the outbreak were included for comparison. All GAS isolates from children attending the day-care center, including those from streptococcal TSS cases, shared the same emm type 4, genomic pattern by PFGE (A) and toxin-gene profile. Neither the emm type nor the PFGE pattern or toxin gene profile of the outbreak-associated strains were encountered among GAS isolated from household or staff contacts. A clone of GAS belonging to emm type 4 and characterized by a specific PFGE pattern and toxin-gene profile was responsible for a community outbreak of streptococcal TSS disease in a child day-care center in Spain. This is the first day-care outbreak reported in our country.

Group A Streptococcal Cysteine Protease Degrades C3 (C3b) and Contributes to Evasion of Innate Immunity

A relative lack of neutrophils around Streptococcus pyogenes is observed in streptococcal toxic shock syndrome (STSS). Because the bacteria spread rapidly into various organs in STSS, we speculated that S. pyogenes is equipped with molecules to evade the host innate immune system. Complement C3b opsonizes the pathogen to facilitate phagocytosis, and a complex of C3b converts C5 into anaphylatoxin. Because we found that C3 (C3b) is degraded in sera from patients with STSS, we investigated the mechanism of C3 (C3b) degradation by S. pyogenes. We incubated human C3b or serum with recombinant SpeB (rSpeB), a wild-type S. pyogenes strain isolated from an STSS patient or its isogenic DeltaspeB mutant and examined the supernatant by Western blotting with anti-human C3b. Western blot and Biacore analyses revealed that rSpeB and wild-type S. pyogenes rapidly degrade C3b. Additionally, C3 (C3b) was not detected in sera collected from infected areas of STSS patients. Furthermore, the survival rate in human blood and in mice was lower for the DeltaspeB mutant than the wild-type strain. Histopathological observations demonstrated that neutrophils were recruited to and phagocytosed the DeltaspeB mutant, whereas with the wild-type strain, few neutrophils migrated to the site of infection, and the bacteria spread along the fascia. We observed the degradation of C3 (C3b) in sera from STSS patients and the degradation of C3 (C3b) by rSpeB. This suggests that SpeB contributes to the escape of S. pyogenes from phagocytosis at the site of initial infection, allowing it to invade host tissues during severe infections.

Streptococcal toxic shock syndrome in North Queensland—a case controlled review of clinical and molecular determinants

Streptococcal toxic shock syndrome (STSS) is an uncommon but important complication of invasive group A streptococcal (GAS) disease. A number of clinical risk factors and molecular markers have been linked with STSS. We report here a case controlled review looking specifically at cases of STSS from North Queensland, between 1996 and 2005. All isolates obtained were cultured from sterile sites. Of these, there were 25 cases which fulfilled the criteria for STSS. These were matched for age, sex and ethnicity with 31 cases of invasive GAS without STSS. Indigenous patients represented 16% of the group. Mortality was significantly higher (28%) in the STSS group. Necrotising fasciitis and an elevated serum creatinine on admission were significantly associated with STSS. There was no significant difference in the presence of risk factors or mean total white cell count in both groups. There was also no significant difference in the presence of streptococcal pyrogenic exotoxins a, c, g, h and ssa, prtF1, mean internalization efficiency, biotypes or emm types, in isolates involved. Although not statistically significant, there was a trend for prtF2 to be associated with STSS.

Síndrome del shock tóxico estreptocócico: experiencia de los últimos 10 años en un hospital terciario

In the last two decades there has been a reported increase in the incidence of streptococcal toxic shock syndrome (STSS). The objective of this study was to determine the clinical and epidemiological characteristics of this infection. Retrospective study of all cases of STSS diagnosed at a single tertiary hospital over the last ten years. We report 13 cases of STSS (8 men, mean age 62 years). The mean annual incidence was 0.19 episodes/100,000 population from 1994 to 1998 and 0.53 episodes/100,000 population from 1999 to 2003 (p = 0.059). All patients had at least one underlying disease and there were no intravenous drug users. The most common portals of entry were the skin and soft tissues (85%) and all but one patient had a positive blood culture. Two cases were nosocomial and five patients required surgery (amputation and/or debridement). There was a high mortality rate (85%) and a rapid course from onset to death; nine patients died within four days after establishing the diagnosis. The incidence of SSTS has increased over the last five years at our hospital. Elderly patients with underlying medical conditions were more susceptible to acquiring this infection. Early mortality was very high.

Inverse relation between disease severity and expression of the streptococcal cysteine protease, SpeB, among clonal M1T1 isolates recovered from invasive group A streptococcal infection cases.

The streptococcal cysteine protease (SpeB) is one of the major virulence factors produced by group A streptococci (GAS). In this study we investigated if differences exist in SpeB production by clonally related M1T1 clinical isolates derived from patients with invasive infections. Twenty-nine of these isolates were from nonsevere cases and 48 were from severe cases, including streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) cases. The expression and amount of the 28-kDa SpeB protein produced were determined by quantitative Western blotting, and protease activity was measured by a fluorescent enzymatic assay. A high degree of variation in SpeB expression was seen among the isolates, and this variation seemed to correlate with the severity and/or clinical manifestation of the invasive infection. The mean amount of 28-kDa SpeB protein and cysteine protease activity produced by isolates from nonsevere cases was significantly higher than that from STSS cases (P = 0.001). This difference was partly due to the fact that 41% of STSS isolates produced little or no SpeB compared to only 14% of isolates recovered in nonsevere cases. Moreover, the cysteine protease activity among those isolates that expressed SpeB was significantly lower for STSS isolates than for isolates from nonsevere cases (P = 0.001). Increased SpeB production was also inversely correlated with intact M protein expression, and inhibition of cysteine protease activity blocked the cleavage of the surface M protein. Together, the data support the existence of both an "on-off" and a posttranslational regulatory mechanism(s) controlling SpeB production, and they suggest that isolates with the speB gene in the "off" state are more likely to spare the surface M protein and to be isolated from cases of severe rather than nonsevere invasive infection. These findings may have important implications for the role of SpeB in host-pathogen interactions via regulation of the expression of GAS virulence genes and the severity of invasive disease.

Comparison of pathogenic factors expressed by group A Streptococci isolated from patients with streptococcal toxic shock syndrome and scarlet fever

Streptococcal toxic shock syndrome (STSS) is an illness with high mortality. To obtain clues to understanding the pathogenesis of STSS, we investigated the expression of several pathogenic factors in ten group A streptococcus (GAS) isolates from ten patients with STSS in Japan, in comparison with ten GAS isolates from children with scarlet fever. The ten scarlet fever-derived GAS isolates were equally low in lethality and anti-phagocytic activity in mice and in the production of streptolysin O (SLO), and equally high in production of superantigenic exotoxins (SAGTs) and cysteine proteinase. By comparison, the ten STSS-derived GAS isolates were heterogeneous in the expression of the above pathogenic factors, which ranged from low to high values. Most of the ten STSS-derived isolates were higher in lethality and anti-phagocytic activity and production of SLO, and lower in the production of SAGTs and cysteine proteinase than the ten scarlet fever-derived isolates. The results suggest that the lethality and anti-phagocytic activity examined in mice and SLO may be involved mainly in the development of most of the ten STSS cases.

Risk factors in the pathogenesis of invasive group A streptococcal infections: role of protective humoral immunity.

An impressive change in the epidemiology and severity of invasive group A streptococcal infections occurred in the 1980s, and the incidence of streptococcal toxic shock syndrome cases continues to rise. The reason for the resurgence of severe invasive cases remains a mystery-has there been a change in the pathogen or in host protective immunity? To address these questions, we have studied 33 patients with invasive infection caused by genotypically indistinguishable M1T1 strains of Streptococcus pyogenes who had different disease outcomes. Patients were classified as having severe (n = 21) and nonsevere (n = 12) invasive infections based on the presence or absence of shock and organ failure. Levels of anti-M1 bactericidal antibodies and of anti-streptococcal superantigen neutralizing antibodies in plasma were significantly lower in both groups than in age- and geographically matched healthy controls (P < 0.01). Importantly, the levels of these protective antibodies in plasma samples from severe and nonsevere invasive cases were not different. Together the data suggest that low levels of protective antibodies may contribute to host susceptibility to invasive streptococcal infection but do not modulate disease outcome. Other immunogenetic factors that regulate superantigen responses may influence the severity of systemic manifestations associated with invasive streptococcal infection.

Report of surveillance on streptococcal toxic shock syndrome in Japan and presentation of the criteria

A survey was made on the situation of Group A Streptococcal toxic shock syndrome (STSS) based on questionnaires. The survey was divided into two parts. The first survey was done by sending out an outline of the STSS inquiring if any STSS cases were observed by mail to university hospitals, residence training hospital and other major hospitals totaling 2512 institutes. The second survey was subsequently done to the institutes that had STSS cases asking for the clinical course, data and sampling of the bacteria. The diagnosis of STSS was confirmed based on the diagnostic criteria induced by the working group of the United States. We have found 97 cases of STSS which 48.5% had fatal outcomes. There was no significant sex difference in the onset or the mortality rate. It occurred more in the older population, and occurred through out Japan but was not found to be epidemic. The first case was backed in 1978 and it began to increase since 1993, reaching its peak in 1994 and now decreasing in number. Most of the isolated Group A streptococcus were of type M1 and M3. We have modified the United States diagnostic criteria creating a new Japanese criteria, which includes the symptoms of the central nervous system in the term MOF. The aim for the Japanese criteria is to search for the etiology of the disease. The Japanese criteria requires that the disease progresses rapidly and that the patient be free from any conditions that might suppress the immunal system.

Plasma from patients with severe invasive group A streptococcal infections treated with normal polyspecific IgG inhibits streptococcal superantigen-induced T cell proliferation and cytokine production.

Previous studies have suggested a central role for superantigen-induced immune responses in the pathogenesis of streptococcal toxic shock syndrome. The production of streptococcal superantigens by clinical group A streptococcal (GAS) isolates was studied, and the ability of plasma collected from patients with severe invasive GAS infections to neutralize the proliferative- and cytokine-inducing activities of these superantigens was investigated. Overnight culture supernatants from all GAS isolates obtained from patients with invasive disease were found to contain superantigenic activity, as evident from their ability to drive potent T cell proliferation, induce high production of cytokines, and stimulate T cells in a V beta-specific manner. Twelve patients with severe invasive GAS infections, including 11 streptococcal toxic shock syndrome cases and one necrotizing fasciitis without shock, were treated with i.v. infusions of normal polyspecific Ig (IVIG). Plasma samples collected from each patient before and after IVIG administration were analyzed for their ability to neutralize the activity of streptococcal superantigens produced by the GAS isolate that caused their disease. In all IVIG-treated patients, the capacity to neutralize the superantigenic activity, produced by their respective GAS isolate or by purified streptococcal pyrogenic exotoxins, increased in plasma following IVIG administration. Of particular clinical relevance, post-IVIG plasma from each patient completely blocked cytokine production elicited by their respective GAS culture supernatants or by purified streptococcal pyrogenic exotoxins. This study shows that IVIG treatment confers in vivo inhibitory activity against a large array of streptococcal superantigens and suggests that IVIG may be useful in the treatment of severe invasive streptococcal infections.