Toxic shock syndrome caused by a strain of Staphylococcus aureus that produces enterotoxin C but not toxic shock syndrome toxin-1

An 8-month-old infant presented with pneumonia and pleural effusion associated with clinical manifestation of toxic shock syndrome. A Staphylococcus aureus strain isolated from the pleural fluid produced enterotoxin C, but not toxic shock syndrome toxin-1 or other enterotoxins. Acute and convalescent sera showed an antibody rise to enterotoxin C but not to toxic shock syndrome toxin-1. These findings support the possibility that enterotoxin C was the primary toxin associated with this infant's illness.     

Possible relationship between streptococcal pyrogenic exotoxin A and Kawasaki syndrome in patients older than six months of age

BACKGROUND: We previously investigated antibody titers against four kinds of superantigens [streptococcal pyrogenic exotoxin A (SPEA), streptococcal pyrogenic exotoxin C, toxic shock syndrome toxin-1 and staphylococcal enterotoxin B] in patients with Kawasaki syndrome (KS) younger than 6 months of age and reported a relationship between toxic shock syndrome toxin-1 and KS patients. In this study we have investigated antibody titers in KS patients older than 6 months of age. METHODS: Serum of 81 patients with KS older than 6 months of age, before intravenous gamma-globulin therapy, and 88 normal age-matched children were used in this study. The IgG antibody titers against four kinds of superantigens were measured with an enzyme-linked immunosorbent assay. RESULTS: The KS patients showed significantly elevated mean SPEA titer (P = 0.006) and significantly higher incidence of high SPEA (P = 0.0024) compared with the controls. The SPEA titer in KS patients showed a significant positive correlation with the number of days from onset of illness (P = 0.0002). CONCLUSIONS: The elevated antibody titer against superantigens of KS patients older than 6 months of age was different from that of KS patients younger than 6 months of age. Our results suggest that KS patients' exposure to SPEA occurred a few weeks before the onset of KS. SPEA may be one of the possible etiologic agents of KS among patients older than 6 months of age in Kagoshima, Japan.     

A severe case of neonatal toxic shock syndrome-like exanthematous disease with superantigen-induced high T cell response

Most newborn patients with a neonatal type of toxic shock syndrome (TSS), called neonatal TSS-like exanthematous disease (NTED), exhibit mild clinical symptoms. We present the case of a patient with NTED who exhibited exceptionally severe clinical symptoms and an adult-type T cell response to the causative toxin TSS toxin-1.     

A family of selective immunodeficiency with normal immunoglobulins: possible autosomal dominant inheritance

We report here our findings in two Japanese siblings who experienced recurrent bacterial and viral infections since early infancy. Recent symptoms included diarrhoea, conjunctivitis, rashes, headache, sore throat, joint pain, vomiting and vertigo, all similar to those seen in toxic shock syndrome, except for shock. These symptoms improved following gammaglobulin treatment.Staphylococcus aureus with coagulase type IV was continuously isolated from nasal smears producing toxic shock syndrome toxin-1 (TSST-1). Serum antibodies did not or only poorly responded to TSST-1, diphtheria toxoid, varicella virus and rubella virus, whereas total and subclass levels of serum immunoglobulin and in vitro DNA synthesis of lymphocytes stimulated by TSST-1,Staph. aureus, varicella vaccine and mitogens were normal. In the family, ten other members in three generations (five males: five females) including the mother had similar clinical symptoms. Thus, the disease may be inherited in an autosomal dominant fashion.     

Early diagnosis of staphylococcal toxic shock syndrome by detection of the TSST-1 Vbeta signature in peripheral blood of a 12-year-old boy

We report the case of a 12-year-old boy who developed staphylococcal toxic shock syndrome associated with S. aureus pharyngeal colonization or infection. The diagnosis was rapidly confirmed by detecting the Vbeta signature of the toxic shock syndrome toxin-1 in peripheral blood, based on transient T cell depletion rapidly followed by massive expansion of Vbeta 2-positive T cells.     

Neonatal toxic shock syndrome-like exanthematous disease (NTED)

The author and colleagues recently discovered an emerging neonatal infectious disease: neonatal toxic shock syndrome-like exanthematous disease (NTED), which is induced by the superantigen toxic shock syndrome toxin-1 (TSST-1), produced by methicillin-resistant Staphylococcus aureus (MRSA). The massively expanded Vbeta2+ T cells were rapidly deleted in the peripheral blood of patients with NTED. A marked depletion of Vbeta2+ T cells was also observed in the peripheral blood before the expansion of these T cells. Anergy is specifically induced in the TSST-1 reactive T cells of patients with NTED. Rapid recovery from NTED without complications is expected to be related to the induction of immunologic tolerance in neonatal patients. Anti-TSST-1 IgG antibody of maternal origin was found to play a protective role in preventing the development of NTED. The number of hospitals that have experience caring for patients with NTED has increased threefold in the past 5 years. Most MRSA isolates from neonatal intensive care units in Japan were found to be a single clone of coagulase type II and to possess TSST-1 and staphylococcal enterotoxin C genes. The timing and increased incidence of NTED suggest the emergence of a new MRSA clone. By recognizing that TSST-1 can induce NTED, healthcare providers may give increased attention to this disease in neonatal wards.     

Kawasaki Disease: Update on Diagnosis, Treatment, and a Still Controversial Etiology

Diagnosis of Kawasaki syndrome still relies solely on clinical criteria because the etiology is unknown. However, the function and structure of different bacterial superantigens as potential pathogens are discussed. In this regard, the recent determination of the crystal structure of the toxic shock syndrome toxin-1 superantigen complexed with major histocompatibility complex class II suggests potential implications for the controversial findings concerning a role of those superantigens in Kawasaki disease. Although a specific therapy is not available, coronary complications can be significantly reduced with the help of intravenous immunoglobulin therapy combined with oral aspirin.     

Bacterial croup and toxic shock syndrome

An 8-year-old boy with bacterial tracheitis, treated by endotracheal intubation, humidification, airway toilet and antibiotics, experienced a toxic shock syndrome on the day after his admission. The course was favourable. Staphylococcus aureus was isolated from tracheal secretions. Bacterial tracheitis is an infrequent cause of non-menstrual toxic shock syndrome. The diagnosis of bacterial tracheitis should be suspected in a child with toxicity and croup who is not responding to the usual therapy. Endoscopy should be performed allowing for removal of the secretions. The maintenance of a clear airway is the main purpose of the treatment.Abbreviations TSS toxic shock syndrome - CNS central nervous system - CRP C-reactive protein - ICU intensive care unit     

Bullous impetigo: a rare presentation in fulminant streptococcal toxic shock syndrome

Since the mid-1980s, an increase in incidence of invasive disease caused by group A streptococci has been noted among adults and children. The characteristic clinical and laboratory features of the streptococcal toxic shock syndrome include deep-seated infection associated with shock, skin manifestation, and multiorgan failure. However, bullous impetigo is invariably considered to be a staphylococcal disease. Staphylococcus aureus produces an epidermolytic toxin, assumed to be the cause of bullous formation in the skin. Here, we present a case of bullous impetigo in an infant with streptococcal toxic shock syndrome. This is a rare presentation of bullous impetigo caused by group A streptococcus.     

Menstrual toxic shock syndrome in a 17-year-old girl

In a seventeen-year old female patient fever, vomiting, conjunctivitis, pharyngitis, hypotension, exanthema, disorientation and severe myalgia were observed on the second day of menstruation. The typical symptoms suggested the clinical diagnosis of toxic shock syndrome (TSS). During the period of reconvalescence desquamations on hands and feet occurred. From vaginal swabs and the tampons Staphylococcus aureus was recovered. In supernatants from cultures the strain was found to produce toxic shock toxin (TST). Antibodies against TST in the patients serum were not detectable for a period of 70 days after onset of the disease. The patient recovered within three weeks, relapses were not observed.     

Staphylococcal toxic syndrome, atypical presentation of Kawasaki syndrome or staphylococcal skin syndrome?]

CASE REPORT: A three-year-old girl was admitted for persistent fever, erythermatous rash with subsequent desquamation, stomatitis, cheleitis and cervical lymphadenopathy following development of a buttock abscess secondary to an insect bite. A TSS-positive Staphylococcus aureus strain was isolated from the abscess. COMMENTS: Both clinical and bacteriological features led to discuss a "toxic shock syndrome without shock", an atypical form of Kawasaki syndrome without thrombocytosis and coronary arteritis or a staphylococcal skin syndrome. An early treatment with antibiotics could have limited the toxin production explaining both symptomatology and favourable course of the disease.     

Production of antibodies to staphylococcal superantigens in atopic dermatitis.

Staphylococcal superantigens (SAG) are implicated in the inflammation of atopic dermatitis. As SAG mediated diseases may be modified by specific antibodies, the antibody response to SAG in atopic dermatitis was investigated. Immunoglobulin (Ig) G to staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB), and toxic shock syndrome toxin 1 (TSST-1) were measured by sandwich enzyme linked immunosorbent assay (ELISA) in 74 children with atopic dermatitis and 111 controls. Controls had detectable IgG to SEA, SEB, and TSST-1, which increased with age. Atopic dermatitis subjects had an increased response to SEB at 6 months to 2 years (76% v 42%) and 2 to 7 years (79% v 57%), and equivalent responses to SEA and TSST-1, compared to controls. It is suggested that increased responses to SEB relate to increased colonisation and hence exposure to superantigen producing staphylococcus in atopic dermatitis, and that inflammation of atopic dermatitis is not caused by an inability to make antibody to SAG.     

Production of antibodies to staphylococcal superantigens in atopic dermatitis

Staphylococcal superantigens (SAG) are implicated in the inflammation of atopic dermatitis. As SAG mediated diseases may be modified by specific antibodies, the antibody response to SAG in atopic dermatitis was investigated. Immunoglobulin (Ig) G to staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB), and toxic shock syndrome toxin 1 (TSST-1) were measured by sandwich enzyme linked immunosorbent assay (ELISA) in 74 children with atopic dermatitis and 111 controls. Controls had detectable IgG to SEA, SEB, and TSST-1, which increased with age. Atopic dermatitis subjects had an increased response to SEB at 6 months to 2 years (76% v 42%) and 2 to 7 years (79% v 57%), and equivalent responses to SEA and TSST-1, compared to controls. It is suggested that increased responses to SEB relate to increased colonisation and hence exposure to superantigen producing staphylococcus in atopic dermatitis, and that inflammation of atopic dermatitis is not caused by an inability to make antibody to SAG.     

Fulminant liver failure in a child with invasive group A streptococcal infection

Liver involvement is mentioned in streptococcal toxic shock syndrome, but never as fulminant liver failure (FLF). We report the case of a 2-year-old child who developed isolated FLF secondary to invasive group A streptococcal infection without shock due to a M1T1-type strain expressing speA, speB and speC toxin genes. On antibiotics, he recovered rapidly without liver transplantation. CONCLUSION: A streptococcal pyrogenic exotoxin likely constituted the initial insult leading to FLF. This etiology can be included in the differential diagnosis of FLF and would support early introduction of antibiotics.     

Toxic shock syndrome associated with poison oak dermatitis

Toxic shock syndrome commonly occurs in menstruating women, but it is known to be associated with a variety of staphylococcal infections. We report a case of nonmenstrual toxic shock syndrome in an 11-year-old male who presented with altered consciousness and infected poison oak dermatitis of the feet. This is the first reported case of toxic shock syndrome associated with poison oak dermatitis. The signs and symptoms, laboratory findings, and treatment of toxic shock syndrome are reviewed.     

Exfoliative dermatitis in an infant. Association with enterotoxin F-producing staphylococci

A 2-month-old premature infant had an extensive exfoliative dermatitis with flaccid bullae, mucous membrane involvement, thrombocytopenia, and an elevated creatinine kinase level. A subepidermal cleavage plane with numerous necrotic epidermal cells and a polymorphonuclear cell infiltrate were present on a skin biopsy specimen. The isolates of Staphylococcus aureus obtained at the onset of her disease had a 29/52 bacteriophage lysis pattern and produced enterotoxins C and F and epidermal toxin, but no exfolliatins. In toxic shock syndrome (TSS), subepidermal blister formation has been described and a new toxin, epidermal toxin, which causes subepidermal cleavage in the newborn mouse model, has been identified. In some infants, exfoliative dermatitis may be a variant of the well-described TSS in older children and adults.     

Genetic basis of neonatal methicillin-resistant Staphylococcus aureus in Japan

Methicillin-resistant Staphylococcus aureus (MRSA) is still one of major problems of drug-resistant microorganisms and healthcare-acquired infections. Methicillin-resistant Staphylococcus aureus is highly prevalent in patients in neonatal intensive care units (NICU) in Japan. The most predominant MRSA in NICU is multidrug resistant and produces superantigenic exotoxin, toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin C (SEC). These predominant MRSA strains belong to coagulase type II, SCCmec type II, mecA-Tn554 polymorph type I-A and show closely related pulse field gel electrophoresis types. The dissemination of MRSA is wide, and there is a pandemic distribution of a single MRSA clone in the NICU of Japan. Since 1992, the nationwide spread of this clone has also led to the development of a new neonatal disease known as neonatal toxic shock-like exanthematous disease (NTED), which is caused by overactivation of vbeta2+ T cells induced by TSST-1. The spread of MRSA in NICU in Japan has been attributed to overcrowding, high rates of extremely low birthweight babies, understaffing, low control measures of infection and overuse of antibiotics. The environment of NICU and infection control intervention should be improved and a new strategy for control like vaccination or probiotics is required.     

Dosage regimen of arbekacin for methicillin-resistant Staphylococcus aureus infection in newborns and infants

BACKGROUND: Arbekacin (ABK) is an aminoglycoside antibiotic that has a dose-dependent bactericidal action. Because it inhibits the production of toxic shock syndrome toxin-1 (TSST-1) by methicillin-resistant Staphylococcus aureus (MRSA), it has attracted attention as a therapeutic drug for MRSA infection. In this study, the authors investigated the pharmacokinetics of ABK based on therapeutic drug monitoring (TDM), in order to establish an effective dosage regimen with minimal adverse reactions in MRSA infected newborns and infants. METHODS: Arbekacin was administered to nine MRSA infected newborns and infants between October 2000 and March 2002. Following the initial ABK administration, blood was collected and the blood concentration of ABK was measured. The blood concentrations of ABK were analyzed by the two-compartment model or by a model-independent method in order to elucidate the pharmacokinetics of ABK. Pharmacokinetic analysis was performed using WinNonlin Professional V3.1. RESULTS: The mean age at initial ABK administration was 24.0 +/- 26.0 days (postconceptional age: 39.2 +/- 3.9 weeks). The increase in the peak blood concentration of ABK was 2.40 +/- 0.20 microg/mL per mg ABK per kg bodyweight, showing great consistency among cases. The elimination half-life of ABK was 0.22-3.52 h in the alpha phase (T(1/2alpha)) and 2.42-33.44 h in the beta phase (T(1/2beta)), showing great variation among cases. The distribution volume was 0.75 +/- 0.13 L/kg, and systemic clearance was 0.054 +/- 0.012 L/h/kg. ABK alleviated clinical symptoms and inflammations in all cases. CONCLUSION: Nine newborns and infants with MRSA infection and various underlying diseases were successfully treated with TDM-based administration of ABK with no severe adverse reactions.     

Coronary Artery Dilatation in Toxic Shock-Like Syndrome: The Kawasaki Disease Shock Syndrome

Kawasaki disease is a common systemic vasculitis of childhood that may result in life-threatening coronary artery abnormalities. Despite an overlap of clinical features with toxic shock syndrome, children with Kawasaki disease generally do not develop shock. We report two cases of older children who presented with a toxic shock-like illness, and were diagnosed with Kawasaki disease when coronary artery abnormalities were found on echocardiography, in keeping with the recently described ‘Kawasaki disease shock syndrome’. Clinicians should consider Kawasaki disease in all children presenting with toxic shock and assess for coronary artery damage.     

Analysis of tumor necrosis factor-α production and polymorphisms of the tumor necrosis factor-α gene in individuals with a history of Kawasaki disease

BACKGROUND: Tumor necrosis factor (TNF)-alpha plays a central role in the pathogenesis of vasculitis in Kawasaki disease (KD). To address the genetic background of KD, we investigated the level of TNF-alpha production and genetic polymorphisms in the 5' flanking region of the TNF-alpha gene in healthy children with a history of KD. METHODS: For TNF-alpha production, peripheral blood mononuclear cells (PBMC) of children with a history of KD (n = 61) and of non-KD children (n = 35) were stimulated with phorbol 12-myristate 13-acetate, toxic shock syndrome toxin-1 (TSST-1) and the culture supernatant of Staphylococcus aureus derived from a KD patient (S-6), which had several superantigenic activities. The genetic background of KD was addressed by studying polymorphisms in the 5' flanking region of the TNF-alpha gene at positions -1031 (thymine (T) to cytosine (C) change, termed -1031C), -863 (C to adenine (A), -863A), -857 (C to T, -857T), -308 (guanine (G) to A, -308A) and -238 (G to A, -238A) in KD, using dot-blot hybridization with sequence-specific oligonucleotide probes. RESULTS: The PBMC of KD patients with coronary artery lesions produced slightly higher levels of TNF-alpha in response to the bacterial products (such as TSST-1 and S-6). None of the polymorphisms in the 5' flanking region of the TNF-alpha gene were related to KD. CONCLUSIONS: These results suggest that a genetic disposition towards overproduction of TNF-alpha in response to bacterial products may be involved in the pathogenesis of KD.